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****** DATA-MEDICOS **********
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HLA Y COLAGENOSIS 
HLA AND CONNECTIVE TISSUE DISEASES
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****** DERMAGIC-EXPRESS No.57 ******* 
****** 20 MAYO DE 1.999 *********** 
20 MAY 1.999
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EDITORIAL ESPAÑOL
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Hola amigos DERMAGICOS,,,, HLA Y COLAGENOSIS,,, el tema de hoy,,,
Muchas enfermedades dermatológicas y no dermatológicas estan asociadas al sistema HLA (Human Leucocyte Antigen). En estas 51 referencias queda demostrada TOTALMENTE la asociación entre LAS COLAGENOSIS Y EL HLA....

Dr. Leal George (brazil),,, muy buena idea !!! me ayudas con las reevisiones !!!
saludos desde Venezuela,,,

Saludos a TODOS !!!

Dr. Jose Lapenta R.,,,

NO OLVIDEN,,, DERMAGIC/EXPRESS,,,, EL CD,,, MAS DE 1700 REFERENCIAS BIBLIOGRAFICAS EN 52 REVISIONES,,,

PROXIMOS EVENTOS,,, 
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SOCIEDAD VENEZOLANA DE DERMATOLOGíA
UNIVERSIDAD DE CARABOBO
SERVICIO DE DERMATOLOGíA DE LA CIUDAD HOSPITALARIA DR. ENRIQUE TEJERA

1 N 5 A L U D.
22 DE MAYO DE 1.999.

REUNION MENSUAL DE LA S.V.D.

08:00 a.m. a 09:30 a.m.: PRESENTACION DE CASOS CLINICOS~
7( Colagenosis)

Coordinadores: Dr. Raúl Fachín y Dra. Magda A Miret.

09:30 a.m. a 10:00 a.m.: REFRIGERIO.
10:00 a.m. a 10:20 a.m.: LUPUS ERITEMATOSO EN NIÑOS. (Dr. Francisco González - U.C.V.)
10:20 a.m. a 12:00 a.m.:
MESA REDONDA.

Coordinadores: Dr. Raúl Fachin y Dr. Robert Pribyl.

ACTUALIZACION EN COLAGENOPATIAS.
Participantes:
Dra. Blanca Chirivella.
Dra. Miriam Marcano.
Dr. Carlos Facchin 0.
Dra. Maria Elisa Flores.
Dr. Marco T. Mérida.

12:00 m. a 1:00 p.m. REUNION ADMINISTRATIVA.
01:00 p.m. ALMUERZO.

COORDINADORES: Dr. Raúl Fachín Viso - Dr. Carlos Facchln Olavarría y Dra. Alexandra Miret C.

LUGAR: Fundacid, Edf. Escorpio, 3er. piso. Urb. Prebo, Valencia.
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EDITORIAL ENGLISH
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Hello DERMAGICS friends, HLA AND CONNECTIVE TISSUE DISEASES, today's topic. Many illnesses dermatologics and non dermatologics are associated to the HLA system (Human Leucocyte Antigen). In these 51 references it is demonstrated TOTALLY the association between THE HLA AND CONNECTIVE TISSUE DISEASES.

Greetings to ALL, !!

Dr. Jose Lapenta R.,,,
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DERMAGIC/EXPRESS(57)
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HLA Y COLAGENOSIS / HLA AND CONNECTIVE TISSUE DISEASES
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1.) Elevated soluble fas production in SLE correlates with HLA status not with disease activity.
2.) Systemic lupus erythematosus in India.
3.) Systemic lupus erythematosus in a patient whose younger sister had allergic granulomatous angitis.
3.) Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.
4.) Predisposing factors in sulphasalazine-induced systemic lupus erythematosus.
5.) Genetic analysis of TAP2 in systemic lupus erythematosus patients from two ethnic groups.
6.) Elevated serum level of soluble HLA class I antigens in patients with systemic lupus erythematosus.
7.) Detection of antibodies to HIV-1 gp41- and HLA class II antigen-derived peptides in SLE patients.
8.) TNFB gene polymorphism in patients with systemic lupus erythematosus in Korean.
9.) Distributions of HLA class II alleles in autoantibody subsets among Norwegian patients with systemic lupus erythematosus.
10.) Primary antiphospholipid syndrome evolving into systemic lupus erythematosus.
11.) Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La. Comparison with systemic lupus erythematosus and primary Sjogren's syndrome.
12.) Expression of lymphocyte activation markers in benign cutaneous T cell infiltrates. Discoid lupus erythematosus versus lichen ruber planus.
13.) HLA genotypes in a family with a case of homozygous C2 deficiency and discoid lupus erythematosus.
14.) HLA antigens in discoid lupus erythematosus.
15.) Subacute cutaneous lupus erythematosus. Clinical, serologic, and immunogenetic studies of forty-nine patients seen in a nonreferral setting.
16.) Treacher-Collins syndrome and co-existing dermatomyositis 
17.) Association of the HLA-DQA1*0501 allele in multiple racial groups with juvenile dermatomyositis.
18.) Strong association of dermatomyositis-specific Mi-2 autoantibodies with a tryptophan at position 9 of the HLA-DR beta chain.
19.) The Jo-1 antibody system in myositis: relationships to clinical features and HLA.
20.) HLA-DP positive T cells in patients with polymyositis/dermatomyositis.
21.) Clinical, serologic, and immunogenetic studies in patients with dermatomyositis.
22.) Dermatomyositis-like syndrome in X-linked hypogammaglobulinemia. Case-report and review of the literature.
23.) Penicillamine-induced myositis. Observations and unique features in two patients and review of the literature.
24.) Juvenile dermatomyositis: a clinical and immunologic study.
25.) Idiopathic myositis: a rheumatological view.
25.) Penicillamine induced polymyositis and dermatomyositis.
26.) Neonatal lupus erythematosus occurring in identical twins.
27.) Neonatal lupus erythematosus: five new cases with HLA typing.
28.) U1RNP antibody-positive neonatal lupus. A report of two cases with immunogenetic studies.
29.) Neonatal lupus erythematosus: discordant disease expression of U1RNP-positive antibodies in fraternal twins--is this a subset of neonatal lupus erythematosus or a new distinct syndrome?
30.) Immunogenetic study of three Japanese families with neonatal lupus erythematosus.
31.) Neonatal lupus in twins.
32.) New findings in neonatal lupus syndrome.
33.) Neonatal lupus erythematosus. Report of serological and immunogenetic studies in twins discordant for congenital heart block.
34.) Lupus erythematosus profundus with partial C4 deficiency responding to thalidomide.
35.) HLA and clinical associations in systemic sclerosis patients with anti-Th/To antibodies.
36.) Fetal-maternal HLA compatibility confers susceptibility to systemic sclerosis.
37.) Systemic sclerosis (scleroderma): clinical, genetic, and serologic subsets.
38.) Loss of epidermal Langerhans' cells and endothelial cell HLA-DR antigens in the skin in progressive systemic sclerosis.
39.) HLA-DR antigens in progressive systemic sclerosis (scleroderma).
40.) Histocompatibility antigens in progressive systemic sclerosis (PSS; scleroderma).
41.) Clinical relevance and HLA association of autoantibodies against the nucleolus organizer region (NOR-90).
42.) Systemic sclerosis in Iceland. A nationwide epidemiological study.
42.) Association of HLA-DR with progressive systemic sclerosis in Japanese.
43.) The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma).
44.) [Immunogenetic studies of familial occurrence of progressive systemic scleroderma and circumscribed scleroderma]
45.) Expression of HLA class II antigens on skin fibroblasts in scleroderma.
46.) [Scleroderma and HLA antigens]
47.) HLA in systemic scleroderma (PSS) and familial scleroderma.
48.) Immunogenetic analysis of 5 families with multicase occurrence of scleroderma and/or related variants.
49.) A clinical, histological, and immunohistochemical comparison of acrodermatitis chronica atrophicans and morphea.
50.) [Circumscribed scleroderma: internal manifestations and significant correlation to HLA-DR1 and DR5]
51.) T cell reactivity to Sjögren's syndrome related antigen La(SSB) 
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1.) Elevated soluble fas production in SLE correlates with HLA status not with disease activity.
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AU: Rose-LM; Latchman-DS; Isenberg-DA
AD: Department of Medicine, University College London, UK.
SO: Lupus. 1997; 6(9): 717-22
ISSN: 0961-2033
PY: 1997
LA: ENGLISH
CP: ENGLAND
AB: Evidence from animal models of lupus suggests that disruption of Fas-mediated apoptotic events may play a role in systemic lupus erythematosus (SLE). The recently described secreted from of Fas (sFas) could interfere with apoptotic events by blockading Fas/Fas ligand interactions. We describe elevated secreted Fas protein in sera from 60 patients with SLE compared with controls but neither sFas protein nor sFas mRNA levels correlated with disease activity. At the mRNA level there is strong evidence that individuals with human leucocyte antigens common in SLE patients have a genetic predisposition for increased secreted Fas production.

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2.) Systemic lupus erythematosus in India.
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AU: Malaviya-AN; Chandrasekaran-AN; Kumar-A; Shamar-PN
AD: Faculty of Medicine, Kuwait University, Kuwait.
SO: Lupus. 1997; 6(9): 690-700
ISSN: 0961-2033
PY: 1997
LA: ENGLISH
CP: ENGLAND
AB: The first case of systemic lupus erythematosus (SLE) was reported from India in 1995 followed by two more case reports and further, a series of eight cases, till 1969. Since the establishment of a clinical immunology laboratory at a major teaching institution in New Delhi in 1968, SLE was extensively studied and reported from that centre. From mid-1980 onwards several other centres in different regions in India including Chennai (old name Madras), Mumbai (old name Bombay), Calcutta and Hydrabad, also published their regional experience on SLE. Based on these data, the present report describes the clinical and laboratory characteristics of 1366 SLE patients seen in different regions of India. Arthritis, rash, photosensitivity, seizures and psychosis were seen in comparable proportions to other racial groups. Similarly, ANA and anti-DNA antibody positivity was also within the range seen in other racial groups. When compared with other series, however, alopecia, renal lupus, oral ulcers and neurological involvement was seen in higher proportions, reaching statistically significant figures in comparison to some racial groups. In contrast, haematological manifestations were seen in significantly less proportions in comparison to some of the racial groups. Serositis and discoid lesions were also seen in lower proportions than in most of other races. The proportion of those with anti-Sm antibodies was in between two extremes of highest among Africans and Israelis and lowest among Chinese and Europeans. Other manifestations were comparable to most other racial groups. Compared to North American and European reports, significantly low 5 and 10 year survival was observed among patients from India. This could be related to the general public health situation in the country including less than optimal management facilities in hospitals, delay in diagnosis due to lack of awareness of the disease, referral bias where only serious patients reach major city hospitals, or a truly severe disease among Indians, or a combination of these genetic, environmental and/or sociocultural factors. The Main causes of death were irreversible renal damage, infections and neurological involvement. Despite a comparable prevalence of anticardiolipin antibodies (aCL) and lupus anticoagulants (LAC), clinical antiphospholipid syndrome was significantly less common. Genetic studies showed appreciable increase of HLA DR4 (37.5%) among patients compared with controls (18%). Additionally the haplotype B8-DR3 was encountered frequently in the patient 
group.

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3.) Systemic lupus erythematosus in a patient whose younger sister had allergic granulomatous angitis.
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AU: Arakawa-M; Narita-M; Kanda-A; Sasaki-Y
AD: Department of Internal Medicine, Ishinomaki Red Cross Hospital, Japan.
SO: Tohoku-J-Exp-Med. 1997 Jul; 182(3): 253-8
ISSN: 0040-8727
PY: 1997
LA: ENGLISH
CP: JAPAN
AB: A 37-year-old woman visited to our hospital due to general edema. The patient was diagnosed as having systemic lupus erythematosus (SLE) associated with chronic glomerulonephritis, which developed into chronic renal failure and was treated with regular hemodialysis. The patient's younger sister had been followed in our outpatient's clinic because of allergic granulomatous angitis (AGA). The sibling's common histocompatibility leukocyte antigens (HLA) were A24(9), B52(5), and DR2.

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3.) Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.
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AU: Stassi-G; Todaro-M; De-Maria-R; Candore-G; Cigna-D; Caruso-C; Galluzzo-A; Giordano-C
AD: Laboratory of Immunology, University of Palermo, Italy.
SO: Hum-Immunol. 1997 Jun; 55(1): 39-45
ISSN: 0198-8859
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus erythematosus, Graves' disease, and others, we investigated Fas expression on T and B cells, and sensitivity to Fas-mediated apoptosis of activated T cells, to determine whether abnormalities of the Fas pathway might be associated with the development of autoimmune diseases in this group of individuals. Our findings show that B cells and resting T cells from HLA-B8+, DR3+ subjects express markedly reduced levels of Fas compared with those isolated from HLA-B8-, DR3+ individuals. Reduced levels of Fas were also evident on the surface of T cells from HLA-B8+, DR3+ subjects activated in vitro by stimulation with OKT3 and phytohemoagglutinin. Cycling T cells from these subjects, evaluated for apoptotic nuclei by flow cytometry after incubation with a cytolytic anti-Fas mAb, showed a significantly lower percentage of Fas-mediated apoptosis than did those from HLA-B8-, DR3- individuals. Normal levels of apoptosis were restored after exposure to a synthetic ceramide analog (C2). Further elucidation of the interaction of these molecules in autoimmune diseases may lead to better understanding of the pathogenesis of these disorders.

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4.) Predisposing factors in sulphasalazine-induced systemic lupus erythematosus.
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AU: Gunnarsson-I; Kanerud-L; Pettersson-E; Lundberg-I; Lindblad-S; Ringertz-B
AD: Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
SO: Br-J-Rheumatol. 1997 Oct; 36(10): 1089-94
ISSN: 0263-7103
PY: 1997
LA: ENGLISH
CP: ENGLAND
AB: The aim of this study was to define predisposing factors in patients with sulphasalazine-induced systemic lupus erythematosus (SLE). Eleven patients with onset of SLE or SLE-like syndromes during sulphasalazine treatment are reported. Before the onset of SLE, five of the patients suffered from rheumatoid arthritis (RA), one from psoriatic arthropathy (PsoA), two from juvenile chronic arthritis (JCA) and three from ulcerative colitis (UC). At the time of diagnosis of drug-induced SLE, analysis of antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-histone antibodies (anti-histones), acetylator status of the enzyme N-acetyltransferase 2 (NAT2) and HLA classification were performed. All patients were anti-DNA positive at disease onset and were determined to be slow acetylators. HLA A1 occurred in 4/10 patients, B8 in 5/10. HLA DR 3 was represented in one patient and DR 3(17) in five patients. The DQA1* 0501 allele was observed in 7/10 patients and DQB1 0201* in 6/10. Persistent SLE and development of nephritis were noted in patients with long duration of treatment and high cumulative dose of sulphasalazine (> 1000 g). In sulphasalazine-induced SLE, slow acetylator genotype and HLA haplotypes associated with idiopathic SLE seem to predict disease induction. Further, as the risk of developing persistent SLE and nephritis increases with long-standing sulphasalazine medication, it is of importance to monitor the patients with regard to signs of SLE during the entire treatment period.

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5.) Genetic analysis of TAP2 in systemic lupus erythematosus patients from two ethnic groups.
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AU: Ocal-L; Russell-K; Beynon-H; Cruickshank-K; Lanchbury-JS; Walport-M; Isenberg-D; Briggs-D
AD: Department of Medicine, University College London.
SO: Br-J-Rheumatol. 1996 Jun; 35(6): 529-33
ISSN: 0263-7103
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: The aim of this study was to determine whether the TAP2 (Transporter associated with Antigen Processing 2) locus is involved in susceptibility to systemic lupus erythematosus (SLE). We adopted the interethnic approach to overcome problems in the analysis resulting from linkage disequilibrium. The TAP2 gene polymorphisms of the codons corresponding to amino acid positions 379, 565 and 665 were investigated by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in 186 patients (151 white Europeans, 35 Afrocaribbeans) and 183 controls (79 white Europeans, 104 Afrocaribbeans). In the European SLE patients, the frequency of the TAP2 type V-A-TA was marginally lower compared with the control group (31% vs 42%), with negative linkage disequilibrium between this TAP2 type and DR3 probably accounting for the difference. For the European SLE patients, we confirmed a significant association of DR3 with disease status [odds ratio = 4.16, 95% confidence interval (CI), 2.08-8.39] and in the patients with DR3 there was a significantly high frequency of the TAP2 type V-A-T-. In the Afrocaribbean SLE patients, any associations of disease status with TAP2 phenotype were the inverse of those in the European patients. Thus, in these patients the frequency of V-A-TA was higher than in controls (46% vs 26%, OR = 2.4, 95% CI 1.01-5.74), while the frequency of V-A-T- was lower (26% vs 40%, not significant). Despite possible sampling error, the lack of a difference in TAP2 status between cases and controls within ethnic groups and, if anything, an inverse association across ethnic groups, makes it unlikely that the TAP2 polymorphism studied here is of primary relevance to SLE susceptibility.


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6.) Elevated serum level of soluble HLA class I antigens in patients with systemic lupus erythematosus.
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AU: Tsuchiya-N; Shiota-M; Yamaguchi-A; Ito-K
AD: Department of Medicine and Physical Therapy, University of Tokyo, Japan.
SO: Arthritis-Rheum. 1996 May; 39(5): 792-6
ISSN: 0004-3591
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE: To examine the clinical significance of serum soluble HLA class I antigens (sHLA class I) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Serum levels of sHLA class I were measured by enzyme-linked immunosorbent assay, using a monoclonal antibody against monomorphic determinant of HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human beta 2-microglobulin. RESULTS: The serum sHLA class I concentration was 1.85 +/- 1.15 micrograms/ml (mean +/- SD) in 27 patients with SLE (P < 0.0001 versus normal controls, P = 0.0001 versus RA), 0.61 +/- 0.34 micrograms/ml in 16 patients with RA (P = 0.02 versus normal controls), and 0.41 +/= 0.20 micrograms/ml in normal controls. The HLA class I levels were significantly correlated with the SLE Disease Activity Index (r = 0.62, P = 0.0004) and with a reduction of CH50 levels (r = -0.60, P = 0.0007). A longitudinal analysis of patients with SLE indicated that serum sHLA class I levels fluctuated in conjunction with other disease activity markers. CONCLUSION: Serum sHLA class I may be useful as a disease activity marker of SLE. The mechanism of secretion and the physiologic role of sHLA class I require further study.

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7.) Detection of antibodies to HIV-1 gp41- and HLA class II antigen-derived peptides in SLE patients.
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AU: Koshino-K; Tokano-Y; Hishikawa-T; Sekigawa-I; Takasaki-Y; Hashimoto-H
AD: Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
SO: Scand-J-Rheumatol. 1995; 24(5): 288-92
ISSN: 0300-9742
PY: 1995
LA: ENGLISH
CP: SWEDEN
AB: A role for viruses in the pathogenesis of human autoimmune diseases has long been suspected but has not yet been proven. Highly conserved homologous regions has been reported in the carboxy terminus of human immunodeficiency virus (HIV)-1 gp41 (amino acids 838-844) and the amino-terminal of the beta chain of all human HLA class II antigens (amino acids 19-25). This molecular mimicry between HIV-1 and HLA class II antigens may lead to the generation of autoantibodies and may contribute to the development of autoimmune phenomena in HIV infected patients. We detected antibodies for these homologous peptides from HLA class II and HIV-1 gp41 in systemic lupus erythematosus (SLE) patients without HIV-1 infection. Thirty-seven percent of the SLE patients had IgM antibodies reacting with both HLA class II- and HIV-1 gp41-derived peptides. These results suggest the possibility that a retrovirus may be one of the causative agents of SLE.

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8.) TNFB gene polymorphism in patients with systemic lupus erythematosus in Korean.
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AU: Kim-HY; Lee-SH; Yang-HI; Park-SH; Cho-CS; Kim-TG; Han-H; Kim-DJ
AD: Department of Internal Medicine, Microbiology, Catholic University, Medical College, Seoul, Korea.
SO: Korean-J-Intern-Med. 1995 Jul; 10(2): 130-6
PY: 1995
LA: ENGLISH
CP: KOREA
AB: OBJECTIVES: To elucidate the gene frequency of TNFB Ncol polymorphism and its association with HLA class II antigen in patients with systemic lupus erythematosus(SLE) in Korea. METHODS: We investigated the gene frequency of the TNFB alleles using DNA obtained from peripheral mononuclar cells in 141 healthy controls and in 58 patients with SLE. The polymorphisms of TNFB gene (735 bp) were studied by Ncol PCR-RELP. A portion of TNFB gene(735 bp) was amplified by PCR and its products were digested with Ncol restriction enzyme. The digested samples of amplified DNA were analyzed by agarose gel electrophoresis. TNFB*1 and TNFB*2 alleles were identified according to polymorphic fragments on Ncol restriction site in the first intron of the TNFB gene. The generic types of HLA-DRBI were also determined by PCR with sequence specific primers(SSP) using genomic DNA from the same subjects. RESULTS: The genotypic frequency of TNFB*2 homozygote was significantly increased in patients with SLE compared with controls(RR = 2.36, P = 0.011). The frequency of HLA-DRBI*15 was also significantly increased in patients (RR = 2.27, P = 0.029). However, the increased frequency of TNFB*2 homozygote was apparently increased in nephritis group (RR = 2.79, P = 0.035), whereas the significance of TNFB*2 homozygote was weakend in non-nephritis group. CONCLUSIONS: Our results suggest that genetic predisposition of TNFB*2 homozygote is another risk factor in Korean SLE, especially in DR2 negative patients. In addition, TNFB*2 homozygote could have a tendency for the development of nephritis in patients with SLE.

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9.) Distributions of HLA class II alleles in autoantibody subsets among Norwegian patients with systemic lupus erythematosus.
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AU: Skarsvag-S; Hansen-KE; Moen-T; Eggen-BM
AD: Department of Immunology and Bloodbank, Trondheim Regional Hospital, University of Trondheim, Norway.
SO: Scand-J-Immunol. 1995 Nov; 42(5): 564-71
ISSN: 0300-9475
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: In order to find potential correlations between HLA class II alleles and anti-SS-A, -SS-B, -Sm and anti-snRNP responses among Norwegian patients with systemic lupus erythematosus (SLE), HLA-DRB1, -DRB3*0101, -DQA1 and -DQB1 alleles were determined by DNA typing 50 patients and 108 controls. HLA distributions were analysed in the following autoantibody subgroups: anti-SS-A with -SS-B, anti-SS-A without -SS-B, anti-snRNP without -Sm, anti-SS-A without -snRNP and anti-snRNP without -SS-A. The autoantibodies were detected by EIA (enzyme immunuassay). Patients with anti-SS-A and -SS-B had significantly increased frequencies of DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201 (in linkage disequilibrium) versus controls and versus patients without anti-SS-A and -SS-B. No differences in HLA distribution were found when the group with anti-SS-A alone was compared to the group with anti-SS-A and concomitant -SS-B. Comparing the groups with and without anti-SS-A and -SS-B, the highest RR were found for the alleles DRB1*03, DRB3*0101, DQB1*0501, DQB1*0201 (in linkage disequilibrium) with RR: 16.8, 5.0, 19.6, 10.3, respectively, P < 0.05). RR for DQw2/DQw6 heterozygotes was 3.5 (Ns.), and RR for cases having DQ alpha molecules with glutamine in position 34 and DQ beta molecules with leucine in position 26 on both chains was 6.3 (P < 0.05). No HLA associations were observed in the group with anti-snRNP without concomitant -Sm or without concomitant -SS-A. These results show that production of anti-SS-A and -SS-B is associated to the HLA alleles DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201, and that this haplotype shows stronger correlation to these responses than DQw2/DQw6 heterozygosity or HLA molecules having glutamine in position 34 (DQ alpha) and leucine in position 26 (DQ beta). The failure to observe any correlation with DRBI*15,16 (DR2) in the group with anti-SS-A alone may demonstrate ethnic differences concerning this response. The failure to identify any HLA associations for the anti-snRNP response may reflect the heterogeneity of the molecules that constitute this antigen.

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10.) Primary antiphospholipid syndrome evolving into systemic lupus erythematosus.
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AU: Mujic-F; Cuadrado-MJ; Lloyd-M; Khamashta-MA; Page-G; Hughes-GR
AD: Lupus Arthritis Research Unit, Rayne Institute, St. Thomas' Hospital, London, UK.
SO: J-Rheumatol. 1995 Aug; 22(8): 1589-92
ISSN: 0315-162X
PY: 1995
LA: ENGLISH
CP: CANADA
AB: Since 1983 we have followed a total of 165 patients with antiphospholipid syndrome (APS). During the median followup period of 78 mo (range 12-336 mo), 3 of 80 patients with primary APS subsequently developed features of systemic lupus erythematosus (SLE) or lupus-like disease. One patient developed lupus-like disease 4 yrs and the other 2 developed full blown SLE more than 10 yrs after initial presentation of primary APS. Tissue typing in patients who developed SLE showed HLA antigens A2, A3, B35, Bw6, Cw4, DR7, DRw53, and DQ2 (Case 2); and A1, A3, B7, B8, Bw6, Cw7, DR4, DR15, DR51, DRw53, and DQ1 (Case 3). We report clinical features and genetic associations of these 3 patients.

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11.) Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La. Comparison with systemic lupus erythematosus and primary Sjogren's syndrome.
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AU: Julkunen-H; Siren-MK; Kaaja-R; Kurki-P; Friman-C; Koskimies-S
AD: Fourth Department of Medicine, Helsinki University Central Hospital, Finland.
SO: Br-J-Rheumatol. 1995 Oct; 34(10): 901-7
ISSN: 0263-7103
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II antigens, and the results were compared with the corresponding HLA types in 900 healthy controls, in 45 mothers with systemic lupus erythematosus (SLE) and in 21 mothers with primary SS who had healthy children. An enzyme-linked immunosorbent assay was used to study the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens. Mothers of children with CHB had HLA B8 and DR3 significantly more often than healthy controls [71 vs 10%; relative risk (RR) 9.8, P < 0.00001 and 74 vs 23%; RR9.8, P < 0.001, respectively]. HLA B35 was protective (RR 0.1, P = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively), and compared to controls with primary SS less often HLA B15 positive (RR 0.1, P = 0.010). In general, the HLA antigen profile in mothers of children with CHB was more closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of children with CHB than in controls with SLE and primary SS (P = 0.0001-0.0014). With regard to SS-B/La, the autoantibody responses were similar (P = 0.32-0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

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12.) Expression of lymphocyte activation markers in benign cutaneous T cell infiltrates. Discoid lupus erythematosus versus lichen ruber planus.
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SO - Acta Derm Venereol 1989;69(4):292-5
AU - Sundqvist KG; Wanger L
AB - The expression of lymphocyte activation markers (IL2 receptors, transferrin receptors and HLA-DR) was examined in cutaneous lymphoid infiltrates of 12 patients with lichen ruber planus (LP) and 10 individuals with discoid lupus erythematosus (DLE). The cell infiltrates in both conditions were generally of considerable size. The vast majority of the infiltrating cells were T cells. The reactivity of the anti-IL2 receptor antibody used was confined to lymphocytes. In patients with LP 26 +/- 17% of the infiltrating cells were IL2 receptor positive, 20 +/- 8% carried transferrin receptors and greater than 90% HLA-DR. In patients with DLE less than 1% were IL2 receptor positive, less than 5% carried transferrin receptors and greater than 90% were HLA-DR positive. These data indicate that IL2 receptor expression distinguishes the infiltrating T-lymphocytes in LP and DLE, although in both conditions the vast majority of the infiltrating cells were activated as revealed by their expression of HLA-DR.

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13.) HLA genotypes in a family with a case of homozygous C2 deficiency and discoid lupus erythematosus.
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SO - Acta Derm Venereol 1986;66(5):419-22
AU - Braathen LR; Bratlie A; Teisberg P
AB - A fifty-year-old man with a history of recurrent bronchial and renal infections, and rheumatoid arthritis was admitted with a sunexposure-induced discoid lupus erythematosus. Complement levels and HLA typing of the patient and his family revealed a homozygous C2 deficiency in the patient and his HLA-identical healthy younger sister. The C2 deficiency gene was associated with HLA-A10, B18, DR2, C4A4B2, BfS on one chromosome and with HLA-A2, B7, DR2, C4A4B2, BfS on the other.

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14.) HLA antigens in discoid lupus erythematosus.
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SO - Acta Derm Venereol 1982;62(2):155-7
AU - Tongio MM; Fersing J; Hauptmann G; Mayer S; Grange D; Samsoen M; Groshans E
AB - HLA-A, B, C and Bf typing was performed in 55 cases of Discoid Lupus Erythematosus (DLE). When both the sex and age of the patient at the onset of the disease were taken into consideration (group I under 40 years, group II over 40), the following increases in antigen frequency were observed: group I: A2 in women, B5, A10 in men; group II: Aw19.2 in women, B8 in both sexes. Nevertheless, if the probability is multiplied by the number of antigens tested, these results are no longer significant.

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15.) Subacute cutaneous lupus erythematosus. Clinical, serologic, and immunogenetic studies of forty-nine patients seen in a nonreferral setting.
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SO - J Am Acad Dermatol 1986 Dec;15(6):1227-37
AU - Callen JP; Kulick KB; Stelzer G; Fowler JF
AB - Subacute cutaneous lupus erythematosus has been clearly recognized as a distinct cutaneous manifestation of lupus erythematosus. Two forms have been described, an annular erythema and a papulosquamous variant. Previous data have suggested that these patients have a high incidence of mild to moderate systemic disease, anti-Ro (SS-A) antibodies, and human lymphocyte antigen (HLA)-DR3, particularly the annular form. We studied forty-nine patients with subacute cutaneous lupus erythematosus seen in local private practices in our area. Lesions of chronic cutaneous lupus erythematosus were seen in 34.8% of our patients. Twenty-five patients (51%) fulfilled the American Rheumatism Association criteria for the classification of systemic lupus erythematosus, and renal disease was present in nine of these patients (including 3 with decreased function). Antibodies to Ro (SS-A) and/or La (SS-B) were present in only sixteen patients, and HLA-DR3 was found in only seventeen patients. Twenty-two patients had inactive cutaneous disease at follow-up. We concluded that our patient population with subacute cutaneous lupus erythematosus skin lesions is less distinctive than previous literature suggests. The serologic and immunogenetic correlates were not demonstrated. The full range of lupus erythematosus-related disease was seen, although most patients follow a benign course.

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16.) Treacher-Collins syndrome and co-existing dermatomyositis 
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Au: Larenas-Linnemann DE; Berrón-Perez R; Ortega-Martell JA; Onuma-Takane E; Huicochea-Grobet Z 
Ad: Instituto Nacional de Pediatria, Mexico City, Mexico 
So: Ann Allergy Asthma Immunol; 80(1):50-4, 1998 Jan. 
Is: 1081-1206 
Cp: UNITED STATES 
La: Eng 
Ab: BACKGROUND: Treacher-Collins syndrome, an autosomal dominantly inherited malformation of structures derived from the first and second branchial arch, has an incidence of 1:10,000 newborns. The prevalence of dermatomyositis at less than 24 years of age has been estimated at 1 per 100,000. The occurrence of both Treacher-Collins syndrome and dermatomyositis combined in the same patient should occur once in every 1,000,000,000 subjects. METHODS: We report a patient with Treacher-Collins syndrome who developed dermatomyositis at the age of 5 years. RESULTS: No other patient with both Treacher-Collins syndrome and an autoimmune disease has been reported. The thymus originates from the third branchial pouch and is unaffected by the syndrome. In Treacher-Collins syndrome the affected gene has been mapped to the fifth chromosome, while dermatomyositis is related to HLA B8 and DR3, coded on the sixth chromosome. No immunologic alteration has been described in patients with Treacher-Collins syndrome. CONCLUSION: This is the first report of a patient with Treacher-Collins syndrome and dermatomyositis. There is no genetic or physiopathologic explanation for the concurrence of both conditions (Au) 

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17.) Association of the HLA-DQA1*0501 allele in multiple racial groups with juvenile dermatomyositis.
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AU: Reed-AM; Stirling-JD
AD: Department of Pediatrics, University of North Carolina at Chapel Hill, USA.
SO: Hum-Immunol. 1995 Nov; 44(3): 131-5
ISSN: 0198-8859
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: We wanted to determine if HLA-DQA1*0501 is as strongly associated with JDMS in Hispanic and African Americans as it is Caucasians. Using DNA sequencing and oligonucleotide typing, the DNA of 70 JDMS subjects was studied. The HLA-DQA1 allelle DQA1*0501 was present in 13 out of 15 (87%) of the African-American JDMS subjects vs 9 out of 27 (33%) of the African-American controls (p < 0.0009), 12 out of 13 (92%) of the Hispanic JDMS subjects vs 5 out of 18 (28%) of the Hispanic controls (p < 0.0004), and 36 out of 42 (86%) of the Caucasian JDMS subjects vs 36 out of 78 (46%) of the Caucasian controls (p < 0.0009).

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18.) Strong association of dermatomyositis-specific Mi-2 autoantibodies with a tryptophan at position 9 of the HLA-DR beta chain.
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AU: Mierau-R; Dick-T; Bartz-Bazzanella-P; Keller-E; Albert-ED; Genth-E
AD: Research Institute of Rheumatic Diseases, Aachen, Germany.
SO: Arthritis-Rheum. 1996 May; 39(5): 868-76
ISSN: 0004-3591
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE: To characterize the clinical and immunogenetic features of patients with Mi-2 autoantibodies. METHODS: Eighteen adult white patients with Mi-2 antibodies were clinically characterized and compared with 41 Mi-2-negative dermatomyositis (DM) patients. HLA class I and class II typing for DRB alleles was done by microcytotoxicity assay and for DQA and DQB alleles by polymerase chain reaction-based oligotyping. RESULTS: Seventeen of the 18 Mi-2-positive patients had DM. Symptoms of scleroderma, lung involvement, and arthritis were less common in this group than in the Mi-2-negative DM patients; the V-sign rash and nailfold involvement were found more frequently. Mi-2 antibodies were strongly associated with HLA-DR7 (88% versus 24% in healthy controls), HLA-DQA1*0201 (86% versus 23%), and DR7 "homozygosity" (31% versus 0%). A tryptophan residue at position 9 of the HLA-DR beta chain was present in all Mi-2-positive patients (100% versus 62%; homozygous in 81% versus 15%). CONCLUSION: Our results reemphasize the specificity of Mi-2 antibodies for DM, and extend previous reports that Mi-2 antibody production is associated with certain HLA class II antigens. We propose beta 9-Trp as a candidate epitope on the HLA-DR beta chain as a prerequisite for this type of autoimmune response.
MESH: Adult-; Amino-Acid-Sequence; Antibody-Specificity; Base-Sequence; Dermatomyositis-physiopathology; Epitopes-immunology; HLA-DR-Antigens-genetics; HLA-DR-Antigens-immunology; Middle-Age; Molecular-Sequence-Data; Oligonucleotide-Probes-genetics; Tryptophan-genetics

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19.) The Jo-1 antibody system in myositis: relationships to clinical features and HLA.
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SO - J Rheumatol 1981 Nov-Dec;8(6):925-30
AU - Arnett FC; Hirsch TJ; Bias WB; Nishikai M; Reichlin M
AB - Antibodies to Jo-1, a saline extractable nuclear antigen, were found in 11/47 (23%) patients with myositis and in 0/35 controls with systemic lupus erythematosus or progressive systemic sclerosis (p less than or equal to 0.01). Within myositis subgroups, anti-Jo-1 occurred in 6/20 (30%) with polymyositis, 2/16 (13%) with dermatomyositis and 3/7 (43%) with overlap. There was an association between Jo-1 antibodies and HLA-DR3, irrespective of race or clinical subgroups (p less than or equal to 0.05). All anti-Jo-1 positive patients had either HLA-DR3, HLA-DRW6 or both (p less than or equal to 0.01). Thus, this antibody system might arise as a result of an aberrant immune response mediated at or near HLA-D in patients with myositis.

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20.) HLA-DP positive T cells in patients with polymyositis/dermatomyositis.
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SO - J Rheumatol 1993 Jan;20(1):77-9
AU - Kanai Y; Tokano Y; Tsuda H; Hashimoto H; Okumura K; Hirose S
AB - The examination of HLA-DP+ T cells in 21 patients with polymyositis/dermatomyositis revealed marked increases [28.5% (SD 16.6%)], compared with the HLA-DQ+ and DR+ T cells. The HLA-DP molecule was expressed on both CD4+ and CD8+ T cells. The majority of HLA-DP+ CD8+ cells were cytotoxic T cells. There was no significant correlation between the proportion of HLA-DP+ T cells and the level of myogenic enzyme, although a decrease in HLA-DP+ T cells after therapy was accompanied by a decrease in myogenic enzymes. However, the proportion of HLA-DP+ CD8+ cells was significantly higher in those patients with active pneumonitis.
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21.) Clinical, serologic, and immunogenetic studies in patients with dermatomyositis.
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SO - Acta Derm Venereol 1991;71(4):312-6
AU - Duncan AG; Richardson JB; Klein JB; Targoff IN; Woodcock TM; Callen JP
AB - Dermatomyositis is a disease of unknown etiology characterized by progressive, symmetrical, proximal muscle weakness with accompanying compatible cutaneous findings. Thirty-nine patients with dermatomyositis from the Louisville, Kentucky area were enrolled in this study. Patients were grouped into those with or without a malignancy. Ten patients (26%) either had or have had a malignancy. Twenty-five Caucasian patients were HLA typed for the A, B, DR and DQ locus antigens, of whom 5 had an associated malignancy and 20 did not have a malignancy. We found that no single antigen had a significantly increased or decreased frequency as compared with our control population for the entire group, or for any clinical subset we examined. Serologic testing revealed 4 patients with anti-Mi-2 antibodies and 1 patient with anti-PM-SCL antibodies. No patient had a positive anti-Jo-1 antibody in this group. The results of serologic tests in this group did not correlate with any clinical subset or HLA antigen. Our findings were in agreement with the previous reports in which approximately 25% of patients with DM have an associated malignancy. Our findings also support the notion that untargeted malignancy searches are not warranted. Contrary to previous reports we did not observe an inverse relationship between cancer and pulmonary disease in the dermatomyositis patient. This study does not indicate that there are any HLA associations or clinical associations, other than age, that distinguish patients with dermatomyositis as running a greater risk of developing malignancy.

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22.) Dermatomyositis-like syndrome in X-linked hypogammaglobulinemia. Case-report and review of the literature.
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SO - Acta Derm Venereol 1990;70(4):309-13
AU - Thyss A; el Baze P; Lefebvre JC; Schneider M; Ortonne JP
AB - A case of dermatomyositis-like syndrome is described in a 19-year-old man with a history of Bruton's hypogammaglobulinemia. Although the patient had central-nervous-system manifestations (seizures), no echovirus was isolated in the cerebrospinal fluid, in contrast to previously reported cases. Data for our case and the 15 cases previously reported in the literature are reviewed. HLA typing of our patient revealed the presence of HLA B8 and DR3, which seems to play a major role in juvenile dermatomyositis.

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23.) Penicillamine-induced myositis. Observations and unique features in two patients and review of the literature.
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SO - Am J Med 1984 Oct;77(4):719-22
AU - Halla JT; Fallahi S; Koopman WJ
AB - Dermatomyositis developed during treatment with penicillamine in two patients with rheumatoid arthritis. Both were male without a history of penicillin allergy. Eosinophilia was present at the start of their illness, and HLA tissue typing showed the presence of HLA-DR2 in one patient. One patient was retreated with penicillamine and remained asymptomatic after three years of therapy, and the other was able to take penicillamine in a reduced dosage.

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24.) Juvenile dermatomyositis: a clinical and immunologic study.
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SO - J Pediatr 1980 Feb;96(2):226-34
AU - Pachman LM; Cooke N
AB - Twenty-one children were diagnosed as having juvenile dermatomyositis on the basis of the strict criteria of Bohan and Peter. In addition to the typical skin and muscle changes, abnormalities of esophageal motility (eight of 19), pulmonary function (14 of 17), ECG (10 of 20), and gastrointestinal absorption of D-xylose (two of eight) with active disease were observed. Clinical signs of other collagen vascular disease appeared in five children. Serologic evaluation demonstrated that ANA and rheumatoid factor were transiently positive in six; one child developed a persistently positive rheumatoid factor after four years of disease inactivity. Antibody to ENA was negative in all, but antibody to PM-1 antigen was present in four of 18. Six had a low C3 or C4; evidence of immune complexes was demonstrated by Clq or Raji binding in eight with active disease. One child was IgA deficient. The HLA-B8 antigen was present in 72% of the Caucasian children as compared with the expected incidence of 21%. Therefore, classical dermatomyositis in children has more systemic involvement then previously appreciated, may be related to the presence of circulating immune complexes, and appears to be under immunogenetic control.

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25.) Idiopathic myositis: a rheumatological view.
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SO - Ann Rheum Dis 1992 Jan;51(1):41-4
AU - Ehrenstein MR; Snaith ML; Isenberg DA
AB - Twenty five patients with idiopathic myositis attended this department for long term follow up from 1980 to 1989. Twelve patients had primary polymyositis (four men, eight women) and six had primary dermatomyositis (three men, three women); five women had an overlap syndrome. Two patients had a malignant condition associated with the myositis. The mean age at diagnosis was 40 years. All of the patients had proximal muscle weakness, 18/25 had a raised creatine kinase value (mean 2325 IU/l), 19/20 had an abnormal electromyogram, and 19/24 had positive muscle biopsy samples. Of the disease specific antibodies, anti-Jo-1 was detected in only 1/21 patients tested (three patients with fibrosing alveolitis were negative for this antibody), but the 56 kDa antibody was detected in 12/17 patients. The HLA data analysed in the white patients (17/25) showed that 6/8 of those tested were HLA-DR3 positive. All patients were treated with prednisolone and azathioprine was used for 14/25 patients. Only three deaths occurred during the eight year follow up, but there was a substantial morbidity, which may reflect the referral pattern. Muscle strength tests and creatine kinase levels were useful in recording the response to treatment in some patients. These data emphasise that careful long term follow up of patients with myositis is mandatory and that although the present treatment strategy has substantially reduced the death rate, morbidity associated with the disease remains a major problem.

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25.) Penicillamine induced polymyositis and dermatomyositis.
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SO - J Rheumatol 1987 Oct;14(5):995-1001
AU - Carroll GJ; Will RK; Peter JB; Garlepp MJ; Dawkins RL
AB - Eight Australian cases of D-penicillamine induced polymyositis/dermatomyositis (PM/DM) are reported. In terms of clinical, pathological and electromyographic features, D-penicillamine PM/DM is similar to idiopathic PM/DM but is generally less severe. Recovery is usually rapid when D-penicillamine is withdrawn. Sera were available for study in 6 of the 8 reported cases. Two of the 6 had elevated titers of acetylcholine receptor autoantibodies. Neither of these patients had clinical signs of myasthenia gravis. In 3 of 6 patients typed for C2, no bands were detected suggesting homozygous C2 deficiency. D-penicillamine PM/DM is associated with HLA-B18, B35 and DR4 and is immunogenetically different from idiopathic PM/DM, rheumatoid arthritis and D-penicillamine myasthenia gravis.

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26.) Neonatal lupus erythematosus occurring in identical twins.
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AU: Shimosegawa-M; Akasaka-T; Matsuta-M
AD: Department of Dermatology, Iwate Medical University, Morioka, Japan.
SO: J-Dermatol. 1997 Sep; 24(9): 578-82
ISSN: 0385-2407
PY: 1997
LA: ENGLISH
CP: JAPAN
AB: The patients were one-month-old identical twins. Scaly erythema was noted mainly on the trunk, face, and scalp of one twin starting about three weeks after birth and starting about two weeks after birth in the other. The patients' courses were observed without treatment; the eruptions tended to disappear two months after birth. The mother had a past history of transient facial erythema. Both twins and mother were positive for antinuclear antibody, anti-SS-A antibody, and anti-SS-B antibody. The histopathological findings corresponded to those of discoid lupus erythematosus (DLE). The class of HLA typing revealed Cw3 in both twins, which is frequently observed in neonatal lupus erythematosus (NLE), and A24 in the mother, which is frequently observed in mothers of babies with NLE.

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27.) Neonatal lupus erythematosus: five new cases with HLA typing.
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SO - Can Med Assoc J 1983 Jul 15;129(2):139-41
AU - Barber KA; Jackson R
AB - In two of five infants with neonatal lupus erythematosus the signs of the disease did not appear until the children had been exposed to direct sunlight. This suggests that an environmental factor may be required for the development of the disease in some patients. Three of the five patients, together with their mothers, had the HLA (histocompatibility) antigens A1 and B8, which supports the concept that individuals may be genetically susceptible to lupus erythematosus.

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28.) U1RNP antibody-positive neonatal lupus. A report of two cases with immunogenetic studies.
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SO - Arch Dermatol 1992 Nov;128(11):1490-4
AU - Dugan EM; Tunnessen WW; Honig PJ; Watson RM
AB - BACKGROUND--Neonatal lupus erythematosus (NLE) is a distinct subset of lupus characterized by cutaneous findings (50%), cardiac conduction defects (50%), and autoantibodies to Ro (SS-A) antigen. HLA typing studies of Ro (SS-A) antibody-positive mothers of infants with NLE have shown an association with the HLA-DR3 phenotype. We report the clinical and serologic features of two infant-mother pairs who are U1RNP antibody positive and Ro (SS-A) antibody negative. HLA typing is reported on these infants, their mothers, and two additional infant-mother pairs with U1RNP antibody-positive lupus whose clinical features have been reported previously. OBSERVATIONS--Cutaneous findings included malar erythema, annular and polycyclic plaques, and scales that resolved with residual telangiectasia and hyperpigmentation 6 months after birth. Systemic abnormalities, including complete heart block, were absent. HLA typing revealed HLA-DR3 in two of four mothers, HLA-DR4 and HLA-DRw53 in two of four mothers, and either HLA-DQ1 or HLA-DQ3 in four of four mothers. No distinct HLA associations were seen in the three infants examined. CONCLUSIONS--The spectrum of cutaneous disease in U1RNP antibody-positive infants is similar to Ro (SS-A) antibody-positive infants with NLE. Complete heart block was not a feature of U1RNP antibody-positive NLE. HLA typing studies show a more diverse immunogenetic pattern in U1RNP antibody-positive mothers of infants with NLE compared with Ro (SS-A) antibody-positive mothers.

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29.) Neonatal lupus erythematosus: discordant disease expression of U1RNP-positive antibodies in fraternal twins--is this a subset of neonatal lupus erythematosus or a new distinct syndrome?
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SO - J Am Acad Dermatol 1995 May;32(5 Pt 2):858-62
AU - Solomon BA; Laude TA; Shalita AR
AB - Neonatal lupus erythematosus (NLE) is an uncommon disease that is manifested by cutaneous lesions, cardiac conduction defects, or both, that appear in utero or shortly after birth. In approximately 95% of patients, anti-Ro antibody (Ro[SS-A]) has been identified and has become the serologic marker for NLE. Since 1987 there have been four reported cases of Ro- and anti-La antibody (La[SS-B])-negative, U1RNP antibody-positive, NLE. Our affected twin, as well as all other infants with U1RNP-positive NLE, had cutaneous lesions similar to those in Ro-positive NLE, although they lacked systemic abnormalities, including cardiac conduction defects. HLA typing of mothers with infants with U1RNP-positive NLE revealed the presence of HLA-DR4, DQw1, or DQw3 phenotypes. Our typing confirms these findings. As with Ro-positive NLE, no distinct HLA associations were demonstrated in the infants. Unlike Ro-positive mothers, all mothers with a U1RNP-positive infant with NLE had connective tissue disease at the time of the diagnosis and had a different spectrum of disease. We describe the clinical, serologic, and immunogenetic findings in the first reported case of U1RNP-positive NLE in dizygotic twins in whom the NLE disease expression was discordant.

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30.) Immunogenetic study of three Japanese families with neonatal lupus erythematosus.
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SO - J Dermatol 1992 Apr;19(4):223-8
AU - Nitta Y; Ikeya T; Santa T; Ohashi M; Usuda T
AB - We encountered three Japanese families with neonatal lupus erythematosus. None of the three fathers showed any signs of collagen disease. The three mothers were found to suffer from Sjogren's syndrome; they all tested positive for anti-SSA and SSB antibodies and had lymphocyte infiltration into the small salivary gland. In two families, one child had neonatal lupus erythematosus while a sibling was normal; in the third family, both children had neonatal lupus erythematosus. Thus, a mother with positive anti-SSA and SSB antibodies can give birth to one infant with and one infant without or have two infants with neonatal lupus erythematosus. We conducted HLA typing of all 12 members of the three families in order to clarify the immunologic factors involved. We found no increased frequency of any HLA phenotype in the three mothers and their four children with neonatal lupus erythematosus; however, HLA-DR4 was present in three of the children with neonatal lupus erythematosus.

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31.) Neonatal lupus in twins.
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SO - South Med J 1989 May;82(5):657-60
AU - Lawrence N; Bligard CA; Storer J; Courrege ML
AB - Neonatal lupus erythematosus (NLE) is a syndrome characterized by one or all of the following elements: cutaneous LE lesions, systemic disease, and congenital heart block. SS-A/Ro and SS-B/La have been implicated in the etiology of NLE, but because NLE is not uniformly manifested in all offspring of SS-A and SS-B autoantibody positive mothers, and because of the wide range of clinical manifestations associated with NLE, other contributing etiologic factors are being explored. HLA studies have revealed that infants of SS-A/Ro and SS-B/La positive mothers bearing HLA-A1, B8, DR3, DQ2, and DR52 are at greater risk of having NLE. Haplotyping in our dizygous twins supports these material HLA associations.

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32.) New findings in neonatal lupus syndrome.
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SO - Am J Dis Child 1984 Mar;138(3):233-6
AU - Lee LA; Weston WL
AB - Neonatal lupus is a syndrome characterized by cutaneous lupus and/or congenital heart block (CHB). This report reviews our original observations on patients with neonatal lupus during the past five years: (1) Sicca syndrome (SS-A) (Ro) autoantibodies were found in the serum of the mothers and infants, were of maternal origin, and constituted a marker for the syndrome. (2) SS-A autoantibodies were found in the majority of the cases of "idiopathic" CHB and may have been the most common cause of all CHBs. (3) Mothers who had one child affected were at risk for having a second child affected. (4) Mothers were often asymptomatic. (5) HLA associations in this syndrome were HLA-DR3, HLA-B8, HLA-MB2, and HLA-MT2, and these occurred in mothers but not infants. Thus, the HLA association was with autoantibody production rather than tissue injury, a finding that may help clarify genetic and environmental roles in autoantibody-mediated disease.


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33.) Neonatal lupus erythematosus. Report of serological and immunogenetic studies in twins discordant for congenital heart block.
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SO - Br J Dermatol 1994 Mar;130(3):342-8
AU - Watson RM; Scheel JN; Petri M; Kan JS; Provost TT; Ratrie H 3rd; Callan NA
AB - Autoantibody, HLA studies and C4 phenotypes were performed on twins discordant for isolated congenital heart block. Serum from the mother and cord blood from the infants revealed Ro(SSA) and La(SSB) antibodies in all three sera. No significant difference in Ro(SSA) antibody titre was noted in the cord blood of either twin when compared with maternal titres, as detected by a sensitive ELISA assay. The infants' mother was HLA-DR3 positive. Both infants had identical HLA and C4 phenotypes. Immunoblot analysis revealed that sera from both mother and infants reacted with the 52-kDa Ro(SSA) macromolecule. Quantitative cord blood IgM levels were not elevated in either twin. This study indicates that placental transfer of anti-Ro(SSA) or anti-La(SSB) alone to the fetus is not sufficient for the expression of congenital complete heart block. We conclude from this experiment of Nature that there must be a second event determining which infant develops complete heart block, but this is unknown at present.

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34.) Lupus erythematosus profundus with partial C4 deficiency responding to thalidomide.
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SO - Br J Dermatol 1991 Jul;125(1):62-7
AU - Burrows NP; Walport MJ; Hammond AH; Davey N; Jones RR
AB - A female patient with disfiguring lupus erythematosus profundus (LEP) from the age of 13 years was found to have an isolated partial C4 deficiency, with reduced levels of both allotypes, C4A and C4B. A genetic basis for the hypocomplementaemia was confirmed by a family study of complement and HLA types which revealed heterozygous null alleles for C4A and C4B in the proband. Marked improvement in her cutaneous lesions occurred with thalidomide.

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35.) HLA and clinical associations in systemic sclerosis patients with anti-Th/To antibodies.
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AU: Falkner-D; Wilson-J; Medsger-TA Jr; Morel-PA
AD: University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
SO: Arthritis-Rheum. 1998 Jan; 41(1): 74-80
ISSN: 0004-3591
PY: 1998
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE. To determine the clinical and immunogenetic features of systemic sclerosis (SSc) patients with anti-Th/To autoantibodies. METHODS. HLA class II alleles were determined by DNA oligotyping in a large group of SSc patients with anticentromere antibodies (ACA), anti-topoisomerase I (anti-topo I), and anti-Th/To autoantibodies. RESULTS. Clinical features of the 28 anti-Th/To-positive SSc patients were similar to those observed in the 56 ACA-positive SSc patients, except for a decreased frequency of gastrointestinal involvement in anti-Th/To-positive patients. Immunogenetic analysis revealed a significant increase in the frequency of HLA-DR11 in the anti-Th/To-positive and the anti-topo I-positive patients. The anti-Th/To-positive patients also had a significant reduction in the frequency of HLA-DR7, similar to that seen in ACA-positive SSc patients. CONCLUSION. Despite clinical and immunogenetic similarities with both the ACA- and anti-topo I-positive patients, anti-Th/To-positive SSc patients present a characteristic pattern of clinical and immunogenetic features that may have implications regarding etiology, pathogenesis, and treatment.

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36.) Fetal-maternal HLA compatibility confers susceptibility to systemic sclerosis.
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AU: Artlett-CM; Welsh-KI; Black-CM; Jimenez-SA
AD: Division of Rheumatology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Room 509, Bluemle Lifesciences Building, 233 South 10th Street, Philadelphia, PA 19107, USA.
SO: Immunogenetics. 1998; 47(1): 17-22
ISSN: 0093-7711
PY: 1998
LA: ENGLISH
CP: UNITED-STATES
AB: Systemic sclerosis (SSc) is a disease of unknown origin, which occurs predominantly in women after childbearing years. There are prominent clinical and histopathologic similarities between SSc and chronic graft-versus-host disease (GVHD). GVHD can occur after blood transfusions or after transplantation with HLA-compatible bone marrow. Here we examined the hypothesis that SSc may be caused by fetal cells crossing the placenta into the maternal circulation and providing donor lymphocytes which recognize disparate HLA antigens, resulting in a reaction similar to chronic GVHD. To test the hypothesis we analyzed the inheritance of HLA class I and class II haplotypes in the families of 37 SSc patients and 42 control individuals. Twenty-six (70.2%) SSc patients had HLA class II alleles compatible either for their offspring or mother, compared with only nine (21%) control individuals. The four patients with juvenile onset SSc we analyzed had alleles compatible with their mothers. These results suggest that in some patients, SSc may, indeed, be a form of chronic GVHD caused by fetal or maternal cells which have crossed the placenta during pregnancy and have remained unrecognized by the host due to class II HLA compatibility, and that subsequent activation of these cells by as yet unknown stimuli result in the development of the disease.

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37.) Systemic sclerosis (scleroderma): clinical, genetic, and serologic subsets.
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SO - J Rheumatol 1987 Jun;14(3):512-8
AU - Livingston JZ; Scott TE; Wigley FM; Anhalt GJ; Bias WB; McLean RH; Hochberg MC
AB - Immunogenetic markers, autoantibodies, and clinical features were studied in 47 patients, 35 Caucasian and 12 black, with systemic sclerosis. Twenty-two had generalized scleroderma, while 25 had limited skin involvement. HLA-DR1 (RR = 2.1, p = 0.08) and DR5 (RR = 2.1, p = 0.08) were increased in Caucasian patients vs controls as was the supertypic specificity HLA-DRw52 (RR = 2.8, p = 0.02, pc = 0.04). HLA-DR6.1 was increased in black patients vs controls (RR = 15.4, p = 0.008, pc = 0.088). There were no significant increases in any of the complement allotypes in either racial group. Anticentromere antibody was noted in 10 patients, all Caucasian; 7 had limited disease. Anti-Scl-70 was noted in 4 patients; all had generalized disease (p = 0.036). HLA-DR2 was present in all anti-Scl-70 positive patients (RR = 22.5, p = 0.006). Our results suggest that clinical subsets of systemic sclerosis can be defined by genetic and serological markers.

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38.) Loss of epidermal Langerhans' cells and endothelial cell HLA-DR antigens in the skin in progressive systemic sclerosis.
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SO - J Rheumatol 1986 Apr;13(2):341-8
AU - Andrews BS; Friou GJ; Barr RJ; Mirick GR; Berman M; Sandborg C; Ross PA
AB - Skin biopsies from the volar aspect of the forearm were studied in 26 patients with progressive systemic sclerosis (PSS) (16 diffuse, 10 CREST) and 4 controls using monoclonal antibodies against Langerhans' cells, T lymphocytes, macrophages, B lymphocytes, NK/K cells and HLA-DR antigen(s). Langerhans' cells were reduced or absent (anti-T6, anti-HLA-DR) in 19 of 20 clinically involved and in all 6 uninvolved PSS skin biopsies. Electron microscopic studies of 3 PSS patients indicated a reduction in the number of Langerhans' cells, with normal morphology of the remaining. HLA-DR antigen(s) on dermal endothelial cells were absent or reduced in 8 of 20 involved and 5 of 6 uninvolved PSS skin biopsies, but were present on the surface of dermal mononuclear cells presumably representing activated T lymphocytes. Increased numbers of dermal macrophages were found in 19% of PSS biopsies compared with controls. Absence of Langerhans' cells appears to represent the most widespread immunopathological feature of PSS. It is also associated with absent endothelial HLA DR surface antigens and activated T lymphocytes within the dermis.

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39.) HLA-DR antigens in progressive systemic sclerosis (scleroderma).
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SO - J Rheumatol 1983 Feb;10(1):128-31
AU - Whiteside TL; Medsger TA Jr; Rodnan GP
AB - Typing at the HLA-DR locus was performed in 125 North American white patients with progressive systemic sclerosis (PSS). We could not confirm associations of PSS with the HLA-DR5 antigen or the HLA-B8/DR3 haplotype. A weak association of the DR1 antigen and PSS with diffuse scleroderma (27.5% vs 11.5% in local controls (corrected p less than 0.05) was observed. HLA-DR1 was significantly associated with the presence of anticentromere antibodies (p less than 0.05), and this combination was found more frequently in individuals with the CREST syndrome variant of PSS. This study failed to identify a clear-cut association between PSS and a genetic factor linked to the major histocompatibility complex.

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40.) Histocompatibility antigens in progressive systemic sclerosis (PSS; scleroderma).
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SO - J Clin Immunol 1982 Oct;2(4):314-8
AU - Lynch CJ; Singh G; Whiteside TL; Rodnan GP; Medsger TA Jr; Rabin BS
AB - Patients with progressive systemic sclerosis (PSS; scleroderma) were typed for the HLA-A, -B, and -DR antigens. No significant differences in the frequencies of any HLA-A or -B antigen were found. In the subgroup of patients with PSS and diffuse scleroderma (PSS-DS), the frequency of Bw35 was increased (0.30 vs 0.17 in controls; p less than 0.005, corrected P greater than 0.2). Although patients with PSS-DS also had an increased frequency of DR1 antigen (0.27 vs 0.12 in local controls; P less than 0.005, corrected P less than 0.05), no association between Bw35 and DR1 antigens could be detected. We found no increase in the frequencies of the DR3 or DR5 antigens in patients with PSS. However, in a subset of PSS patients with pulmonary fibrosis, an increase in DR3 and a decrease in DR4 antigens (P less than 0.005) were observed. Serum antibodies to centromere occurred more frequently in DR1-positive than DR/-negative patients (0.46 vs 0.18; P less than 0.005). This study of a large number of patients with PSS failed to confirm previously reported associations of PSS with the HLA-B8/DR3 haplotype of HLA-DR5 antigen.

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41.) Clinical relevance and HLA association of autoantibodies against the nucleolus organizer region (NOR-90).
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SO - J Rheumatol 1995 Jan;22(1):67-72
AU - Dick T; Mierau R; Sternfeld R; Weiner EM; Genth E
AB - OBJECTIVE. NOR-90 autoantibodies directed against the nucleolus organizer region (NOR) have been described as rare scleroderma associated antibodies. We studied the clinical features of patients with NOR-90 antibodies as well as their HLA phenotype. METHODS. NOR-90 antibodies were detected by indirect immunofluorescence assay using HEp-2 cells, by chromosome spreads as a substrate and in addition by Western blot analysis with HeLa-S3 nucleolar extract. HLA antigens of the NOR-90 antibody positive patients were typed with the standard NIH complement dependent microcytotoxicity test. RESULTS. Nine sera selected by means of the indirect immunofluorescence revealed a typical double band pattern of about 90 kDa identical with the pattern of 2 NOR-90 reference sera by Western blot analysis. Only one patient positive for NOR-90 antibodies suffered from systemic sclerosis (limited cutaneous scleroderma). The other patients with NOR-90 antibodies showed no signs of systemic sclerosis. All patients with NOR-90 antibodies were women and 8 of 9 patients (89 versus 13% of healthy controls, Pcorr 0.001) were positive for the HLA-DR1 allele. CONCLUSION. In contrast to the first report on NOR-90 antibodies we demonstrated no association of these antibodies with systemic sclerosis; however, we found strong evidence for an immunogenetic background of NOR-90 antibody formation.

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42.) Systemic sclerosis in Iceland. A nationwide epidemiological study.
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SO - Ann Rheum Dis 1994 Aug;53(8):502-5
AU - Geirsson AJ; Steinsson K; Guthmundsson S; Sigurthsson V
AB - OBJECTIVES--To investigate the incidence, prevalence and clinical features of systemic sclerosis (SS) in Iceland. METHODS--All patients diagnosed with SS from 1975-90 were included. Retrieval for the study began in 1980 and was carried out by computerised search from registers of all hospitals and health care clinics and death registration files, and with personal communication with doctors in Iceland. RESULTS--Over a 16 year period from 1975-90, 15 new cases were found with an incidence of 0.7 and 0.05/100,000, for females and males at risk respectively, and 0.38 for both sexes. At the end of 1990 there were 18 patients alive with SS, 13 with limited and five with diffuse cutaneous involvement. The age standardised prevalence was 11.9 and 1.5/100,000 for females and males at risk respectively. The crude prevalence rate for both sexes was 7.1/100,000. There were five deaths, two patients died of SS related causes, one had SS renal disease. The relative risk of death was similar to that in the general population. The calculated five year survival rate was 100% and the 10 year survival rate 81%. No HLA antigen association was found. CONCLUSION--Compared with previous surveys this study shows a low incidence of systemic sclerosis and a high proportion of patients with limited cutaneous involvement.

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42.) Association of HLA-DR with progressive systemic sclerosis in Japanese.
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SO - J Rheumatol 1994 May;21(5):857-63
AU - Takeuchi F; Nakano K; Yamada H; Hong GH; Nabeta H; Yoshida A; Matsuta K; Bannai M; Tokunaga K; Ito K
AB - OBJECTIVE. To clarify the contribution of HLA-DR genes to the susceptibility to progressive systemic sclerosis (PSS). METHODS. HLA-DR typing was carried out in 36 Japanese patients with PSS, 42 with systemic lupus erythematosus and 104 healthy subjects by polymerase chain reaction (PCR) method using specific primers and by PCR-SSCP (single-standard DNA conformation polymorphism) method. RESULTS. A haplotype DRB1*1502-DRB5*0102 was significantly increased in PSS (50.0%, p 0.00004, pc 0.001), especially in antitopoisomerase I antibody (a-Scl-70) positive patients (62.5%, p 0.00003, pc 0.001) and PSS with diffuse scleroderma (75.0%, p 0.00001, pc 0.0001). In addition, DRB1*0802 was also increased in DRB1*1502 negative patients with a-Scl-70, (50.0%, p = 0.033, pc = not significant) and in DRB1*1502 negative patients with diffuse scleroderma (75.0%, p = 0.008, pc = not significant). Thus, 81.3% of a-Scl-70 positive patients, and 93.8% of patients with PSS with diffuse scleroderma showed either HLA-DRB1*1502 or 0802. CONCLUSIONS. Our observations show the extreme difference of genetic background of a-Scl-70 positive PSS, with regard to HLA-DR, between Japanese and other ethnic groups including Caucasian and American black persons. The increase in DRB1*1502-DRB5*0102 haplotype supported the hypothesis of Reveille, et al that uncharged polar amino acid residue at position 30 of HLA-DQB1 allele was important for a-Scl-70 positive PSS because close association of the haplotype with DQB1*0601 was well established in Japanese; listed as a hypothetical candidate of PSS susceptible DQB1 allele. DRB1*0802 were also associated with hypothetical candidates of DQ alleles. Furthermore, the sharing of the particular amino acid sequence: valine38 and phenylalanine67-lysine68-glutamic acid69-asparic acid70-arginine71, by DRB5*0102, DRB1*0802 and DR11 (associated with Caucasian PSS) also suggests a contribution of the sequence in HLA-DR molecules to the pathogenesis of PSS according to the shared epitope hypothesis.

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43.) The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma).
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SO - J Clin Invest 1993 Sep;92(3):1296-301
AU - Kuwana M; Kaburaki J; Okano Y; Inoko H; Tsuji K
AB - HLA class II alleles were determined using the PCR-RFLP method in Japanese systemic sclerosis (scleroderma) patients with (n = 28) or without (n = 34) anti-topoisomerase I antibodies (anti-topo I). Either the DQB1*0601 or *0301 allele was recognized in all anti-topo I positive patients, compared with 44% of anti-topo I negative patients (P 0.00001, relative risk [RR] 41) or 58% of Japanese healthy control subjects (P 0.00001, RR 24). Tyrosine at position 26 in the second hypervariable region in the beta 1 domain of the DQB1 gene is common to these two alleles and is not present in any other known DQB1 alleles. We also examined immunoreactivities of anti-topo I positive sera to four different autoantigenic B cell epitopes of topo I molecule that were expressed as recombinant fusion proteins. One major B cell epitope, located within the region corresponding to amino acid residues 74-248, was perfectly associated with the amino acid sequence FLEDR at positions 67-71 in the beta 1 domain of the DRB gene. Two other epitopes, corresponding to 316-441 or 658-700, were associated with the serologically defined HLA-DR52 antigen. Patients with both FLEDR and DR52 demonstrated higher anti-topo I antibody titers. These results suggest that the HLA-DR and DQ genes together control the autoimmune response to topo I in systemic sclerosis.

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44.) [Immunogenetic studies of familial occurrence of progressive systemic scleroderma and circumscribed scleroderma]
TT - [Immungenetische Untersuchungen bei familiarem Vorkommen von progressiver systemischer Sklerodermie und zirkumskripter Sklerodermie.]
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SO - Hautarzt 1992 Sep;43(9):548-53
AU - Holzmann H; Schlieter A; Altmeyer P; Kuhnl P
MC - English Abstract
AB - Two different forms of scleroderma in one family are described: the mother suffers from systemic sclerosis and her daughter from linear morphoea. The observed HLA antigens indicate that systemic sclerosis and morphoea have various features in common. The immunogenetic data can be used to calculate the aetiological and preventive fractions, which together with environmental hazards and other risk factors describe the HLA-associated potential for provocation of scleroderma.

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45.) Expression of HLA class II antigens on skin fibroblasts in scleroderma.
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SO - Br J Dermatol 1992 May;126(5):431-5
AU - Branchet MC; Boisnic S; Bletry O; Robert L; Charron D; Frances C
AB - Skin biopsies were taken from 11 patients with morphoea, nine with acrosclerosis and 10 with diffuse systemic sclerosis and processed for immunohistochemical studies using a panel of monoclonal antibodies including antibodies to MHC class II antigens. A significantly higher percentage of HLA-DR positive dermal cells were observed in the reticular dermis in biopsies from patients with morphoea (44.1 +/- 16.2%), acrosclerosis (15.9 +/- 5.4%) and systemic sclerosis (39.5 +/- 2.3%) when compared with the controls (6.6 +/- 2%). A smaller percentage of dermal cells also expressed HLA-DP and -DQ. The degree of monocnuclear cell infiltrate in the biopsies, however, did not correlate with the percentage of HLA class II positive fibroblasts. In organ culture, the expression of the HLA class II antigens was almost totally lost after 3 days and was no longer detected on fibroblasts after 3 weeks of culture.

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46.) [Scleroderma and HLA antigens]
TT - [Sklerodermie und HLA-Antigene.]
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SO - Hautarzt 1989 Mar;40(3):134-40
AU - Holzmann H; Sollberg S; Schutz K; Kuhnl P
MC - English Abstract
AB - A possible HLA disease association was investigated in 40 patients (38 female, 2 male) with progressive systemic scleroderma (PSS), and 42 patients (32 female, 10 male) with morphea. HLA ABCDR/DQ, glyoxalase and properdin factor B (GLO and BF) phenotypes of patients were compared with 193 healthy controls. Four PSS family studies were performed. The following relative risk (rR) values were determined in PSS: A1 (1.38), A2 (1.39), B8 (1.67), B15 (3.22) and in morphea: A3 (1.43), B7 (1.39), B40 (1.81), BW60 (2.49), DR2 (2.38) and DRW8 (2.55), indicating a relatively weak, HLA-linked genetic predisposition for the manifestation of these dermatological disorders. The HLA "risk" antigens for the two clinically different subtypes of the disease are also different: raised A1/B8 frequencies such as those in our PSS group are related to high (or pathologic) immune response (autoimmune disorders). In contrast, A3 B7 DR2 elevations such as those recorded in our morphea group correlate with low immune response. Following exposition to certain suspected environmental factors (quartz, chemical solvents, drugs, viral fragments), the HLA phenotype may thus predipose some individuals--predominantly women--to different clinical patterns of the disease. HLA typing may thus be useful in clinical differential diagnosis (recent subtyping protocols) and possibly also for determination of the prognosis, i.e. HLA-B8 seems to be related to an acute, inflammatory course of PSS, and HLA-B7/DR2, to rather mild morphea patterns.

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47.) HLA in systemic scleroderma (PSS) and familial scleroderma.
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SO - J Dermatol 1991 Jan;18(1):18-24
AU - Sasaki T; Denpo K; Ono H; Nakajima H
AB - HLA in systemic scleroderma (PSS), including three familial cases, is reported. Three families in which one sister developed PSS and another sister suffered from either PSS (family 1), mixed connective tissue disease (MCTD) (family 2), or Sjogren's syndrome (SjS) (family 3) were described. The elder sister in family 1 died of respiratory insufficiency caused by scleroderma lung. The sisters in family 2 both had SjS, anti SS-A antibodies, and HLA A2-Bw55-Cw1-DRw8 haplotype in common. The elder sister with PSS in family 3 also had SjS and Hashimoto's thyroiditis. HLA in 28 PSS patients including these 3 familial cases were analyzed with 4 MCTD and 4 generalized morphea patients. HLA A2, Bw46, DR2, DRw8, DRw6 and DQw1 antigens were more frequently found in the PSS patients than in the controls. HLA DRw6 was the only antigen that was positive in common in the 3 familial cases. In those patients with anti topoisomerase I antibodies, HLA DR2 antigen was found more frequently than in the controls. Some, but not all, of these results were similar to the previous reports on HLA in PSS. Further investigations on more patients and the other members of these families would be necessary to clarify the significance of these results.


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48.) Immunogenetic analysis of 5 families with multicase occurrence of scleroderma and/or related variants.
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SO - J Rheumatol 1995 Jan;22(1):85-92
AU - Manolios N; Dunckley H; Chivers T; Brooks P; Englert H
AB - OBJECTIVE. To investigate the relative contribution of the major histocompatibility (MHC) gene complex in the etiopathogenesis of familial scleroderma and/or its variants, in 5 Australian families, each with 2 affected members. METHODS. Affected individuals and consenting first degree relatives were examined and had blood collected for histocompatibility leukocyte (HLA) class I, class II antigen, and complement C4 typing. An antinuclear (ANA) profile screen on each family member was performed. RESULTS. Family 1, had 2 affected siblings (scleroderma, CREST), each anticentromere positive ( 1/640 titer), with identical HLA haplotypes. A brother, who was HLA identical to his affected sisters was clinically normal and ANA negative. In Family 2, there were no HLA haplotype similarities between the 2 sisters affected with diffuse scleroderma. Both were ANA positive ( 1/640). A 3rd sister was HLA identical to the proband but was clinically normal and ANA negative. In Family 3, affected siblings (CREST, morphea) had identical HLA haplotypes. In Family 4, both mother (CREST) and one of her 2 daughters (scleroderma) had anticentromere antibodies (1/2560). The unaffected daughter, not sharing either of her sister's haplotypes, was normal and ANA negative. In Family 5, 2 sisters (CREST, CREST) were HLA identical. CONCLUSION. A female predominance in familial scleroderma was observed. There was no common HLA haplotype between different families affected with scleroderma or its disease variants. Within families (except in one case, where the possibility of crossover exists or a question of paternity) affected siblings shared both HLA haplotypes. The development of disease was not totally accounted for by HLA genes, since family members with the same HLA haplotypes as the proband, were not affected. It appears that genes within the MHC complex are required but are not sufficient for the development of systemic sclerosis.

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49.) A clinical, histological, and immunohistochemical comparison of acrodermatitis chronica atrophicans and morphea.
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SO - Am J Dermatopathol 1991 Aug;13(4):334-41
AU - Aberer E; Klade H; Hobisch G
AB - We compared 19 patients with acrodermatitis chronica atrophicans (ACA), a dermatosis caused by Borrelia burgdorferi infection, and 40 patients with morphea, a disease of heterogeneous origin where a borrelia etiology has been suggested in some cases, both clinically and histologically to define the differences between these two dermatoses. Clinically, ACA involves acral body sites with lower temperatures, is seen mostly in elderly persons, and presents as a livid discoloration that is not sharply demarcated. Morphea can be localized in embryonal structures, affects any age and body site, and exhibits extension at the periphery of the lesions. Histologically, ACA shows atrophy of collagen and elastic tissue as well as hypertrophic basophilic elastic tissue; whereas in morphea, sclerosis and polarizing elastic tissue are prominent. Graft-versus-host-like reactions may be present in both dermatoses. Immunohistochemical testing with different lymphocyte markers showed differences only in the expression of HLA-DR antigens. These conditions can be distinguished from each other on a clinical and histological basis in most cases. In 17% of morphea biopsy specimens, however, histological differentiation from ACA was not possible. Moreover, the histological pattern of morphea was not associated with a positive borrelia serology.

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50.) [Circumscribed scleroderma: internal manifestations and significant correlation to HLA-DR1 and DR5]
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TT - [Zirkumskripte Sklerodermie: Interne Manifestationen und signifikante Korrelation zu HLA-DR1 und -DR5.]
SO - Hautarzt 1985 Sep;36(9):516-21
AU - Luderschmidt C; Konig G; Leisner B; Scholz S; Albert EE
MC - English Abstract
AB - In 44 patients with morphea the incidence of internal organ involvement was studied. For the clinical study, only patients with disseminated (22 patients), linear (20 patients), and generalized morphea (2 patients) were considered. Systemic parameters were determined for inflammation and the function of the esophagus, lung, heart and kidneys. In 22 patients, mostly with the linear form of morphea, the muscles were studied by electromyography. In 23 patients the HLA-A, HLA-B, HLA-C and HLA-DR patterns were determined; 27% of the patients showed systemic organ manifestations. Esophagus function was impaired in 10 and lung function in 6 cases; 15 patients showed myositis. The degree of systemic involvement was correlated with the type of morphea and the grade of systemic inflammation. Generalized morphea showed a high rate of organ involvement (2 of 2); in linear morphea organ involvement was reduced to 34% and in the disseminated form, to 14%. There was a significant association of HLA-DR1 and -DR5 with the different types of morphea.

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51.) T cell reactivity to Sjögren's syndrome related antigen La(SSB) 
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Au: Helsloot J; Sturgess A 
Ad: Rheumatology Department, St. George Hospital, Sydney, NSW, Australia 
So: J Rheumatol; 24(12):2340-7, 1997 Dec. 
Is: 0315-162X 
Cp: CANADA 
La: Eng 
Ab: OBJECTIVE. Many patients with primary Sjögren's syndrome (SS) make high titer IgG autoantibodies to the La(SSB) antigen, suggesting antigen specific T cell-B cell interactions. T cell responses to some nuclear antigens, particularly U1RNP, have been detected in patients with systemic lupus erythematosus (SLE) and in healthy subjects. We investigated T cell reactivity to the autoantigen SSB in patients with SS and healthy controls. METHODS. Using the [3H]thymidine proliferation assay, we determined reactivity to purified recombinant SSB (rSSB) in 20 patients with SS and 19 controls. Specificity was determined using tetanus toxoid, endotoxin, and 3 other autoantigens (PBC.M2, Sc170, and GAD). Precursor frequency was calculated by limiting dilution analysis. HLA Class II dependency was investigated using anti-Class II monoclonal antibodies. HLA-DR typing was by polymerase chain reaction and sequence specific oligonucleotide typing. RESULTS. Six of 20 patients with SS and 10/19 controls proliferated to La(rSSB). Precursor frequency of anti-SSB T cells was 1:77,040 and 1:115,000 in 2 healthy subjects and 1:230,250 and 1:103,034 in two patients with SS. Anti-HLA-DR abrogated proliferation to SSB and tetanus toxoid. Thirteen of 15 patients with SS and 4/17 controls were HLA-DR3 positive, with no apparent association of HLA-DR3 with SSB reactivity in controls. CONCLUSION. Anti-La(SSB) specific T cells occur in a significant proportion of controls and in some patients with SS. The function of SSB T cells in controls remains to be defined. They may represent immunoregulatory cells, and further analysis of these cells, and a comparison to those found in patients with SS, may elucidate normal immunoregulation and the derangements that lead to Sjögren's syndrome (Au) 

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DATA-MEDICOS/DERMAGIC-EXPRESS No (57) 20/05/99 DR. JOSE LAPENTA R. 
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