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
✍ Scribed by Karl-Heinz Frank; Monika Füssel; Karsten Conrad; Hans-Peter Rihs; Rainer Koch; Berno Gebhardt; Jürgen Mehlhorn
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 652 KB
- Volume
- 41
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
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.