Different distribution of HLA class II and tumor necrosis factor alleles (TNF-308.2, TNFa2 microsatellite) in anti-topoisomerase I responders among scleroderma patients with and without exposure to quartz/metal dust
| Autor: | Rainer Koch, Frank Kh, Berno Gebhardt, Karsten Conrad, Monika Füssel, Hans-Peter Rihs, Jürgen Mehlhorn |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Systemic disease Genes MHC Class II Immunology Human leukocyte antigen Biology Pathogenesis Rheumatology Immunopathology medicine Humans Immunology and Allergy Pharmacology (medical) Promoter Regions Genetic Autoantibodies Retrospective Studies Autoimmune disease Scleroderma Systemic Tumor Necrosis Factor-alpha Haplotype Dust Quartz Odds ratio medicine.disease Connective tissue disease DNA Topoisomerases Type I Metals Female Microsatellite Repeats |
| Zdroj: | Arthritis & Rheumatism. 41:1306-1311 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/1529-0131(199807)41:7<1306::aid-art22>3.0.co;2-v |
| Popis: | Objective To investigate the influence of quartz/metal dust exposure on the pathogenesis of systemic sclerosis (SSc; scleroderma), by an immunogenetic comparison of HLA class II and tumor necrosis factor (TNF) alleles in patients with and without exposure. Methods A retrospective study of 30 SSc patients exposed to quartz/metal dust (qSSc) and 50 patients with idiopathic SSc (iSSc) was conducted by DNA-based typing of HLA, TNF-308, and TNFa/b microsatellite alleles. Results A neutral or protective haplotype in iSSc anti-topoisomerase I (anti-topo I) responders was found to be a susceptibility haplotype in qSSc patients. HLA-DRB1*0301 (DR3), a component of the extended haplotype HLA-DQA1*0501;B1*0201;DRB1*0301; TNF-308.2;TNFa2/b3, had a decreased frequency in iSSc anti-topo I responders compared with non-responders (P = 0.03, odds ratio [OR] 0.11, 95% confidence interval [95% CI] 0.00-0.95), but a significantly increased frequency in qSSc anti-topo I responders compared with controls and with iSSc anti-topo I responders (P = 0.00004, Pcorr = 0.006, OR 11.38, 95% CI 3.17-44.35 and P = 0.0002, Pcorr = 0.02, OR 30.0, 95% CI 2.05-986, respectively). In contrast, DRB1*1104 (DR5) and DRB1*11/15 (DR5/DR2) with no TNF-308.2 and TNFa2 alleles were prevalent in only the iSSc anti-topo I responders compared with controls (P = 0.0005, Pcorr = 0.04, OR 11.0; 95% CI 2.68-45.93 and P = 0.0002, Pcorr = 0.02, OR 12.43, 95% CI 3.65-40.04, respectively). Conclusion The mechanisms that lead to the development of anti-topo I in qSSc and iSSc patients are suggested to be distinct, although it is not clear that the two diseases themselves are different. |
| Databáze: | OpenAIRE |
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