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/

Objective, To investigate the influence of quartz/metal dust exposure on the pathogenesis of systemic sclerosis (SSc; scleroderma), by an im munogenetic comparison of HLA class II and tumor necrosis factor (TNF) alleles in patients with and without exposure. Methods. A retrospecti ve 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 neutra l or protective haplotype in iSSc anti-topoisomerase I (anti-topo I) r esponders was found to be a susceptibility haplotype in qSSc patients. HLA-DRB10301 (DR3), a component of the extended haplotype HLA-DQA1*0 501;B10201;DRB1*0301; TNF-308.2;TNFa2/b3, had a decreased frequency i n iSSc anti-topo I responders compared with nonresponders (P = 0,03, o dds ratio [OR] 0,II, 95% confidence interval [95% CI] 0,00-0,95), but a significantly increased frequency in qSSc anti-topo I responders com pared with controls and with iSSc anti-topo I responders (P = 0.00004, P-corr = 0.006, OR 11.38, 95% CI 3.17-44.35 and P = 0.0002, P-corr = 0.02, OR 30.0, 95% CI 2.05-986, respectively). In contrast, DRB11104 (DR5) and DRB111/15 (DR5/DR2) with no TNF-308.2 and TNFa2 alleles wer e prevalent in only the iSSc anti-topo I responders compared with cont rols (P = 0,0005, P-corr = 0.04, OR 11.0; 95% CI 2.68-45.93 and P = 0. 0002, P-corr = 0.02, OR 12.43, 95% CI 3.65-40.04, respectively). Concl usion. The mechanisms that lead to the development of anti-topo I in q SSc and iSSc patients are suggested to be distinct, although it is not Clear that the two diseases themselves are different.