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.