SYSTEMIC-SCLEROSIS IN GERMAN URANIUM MINERS UNDER SPECIAL CONSIDERATION OF AUTOANTIBODY SUBSETS AND HLA CLASS-II ALLELES

Systemic sclerosis (scleroderma) is a connective tissue disease with a wide range of clinical manifestations, with high or low degrees of sk in and internal organ involvement together with different antinuclear antibody (ANA) specificities. Several studies provide evidence that ma les, who are rarely affected by systemic sclerosis, have an increased risk when working in mines. Therefore we reinvestigated 21 male subjec ts and 6 cases of deceased male patients who had been engaged in East German uranium mines and had shown evidence of this disease in medical examinations. Dermatological investigations, evaluation of chest X-ra ys and autoantibody estimation were performed. PCR-sequence-specific o ligonucleotide typing was used to study the genetic association of HLA -D alleles with autoantibodies typical for scleroderma in these uraniu m miners suffering from systemic sclerosis and in patients with idiopa thic systemic sclerosis. The determined HLA phenotype frequencies and the following statistical analysis (Fisher's exact test (2-sided)) rev ealed that in comparison with randomly selected controls, alleles DRB1 0300 (DR3) and DQB1*0201 (DQ2) were distinctly increased in the group of affected uranium miners, especially in those with anti-Scl-70 posi tivity. In contrast, we did not observe significant differences betwee n affected and unaffected miners. Comparing anti-Scl-70-positive affec ted uranium miners with anti-Scl-70-positive idiopathic systemic scler osis cases, DRB10300 as well as DQB1*0201 were also significantly enh anced in the former group. ACA-positive systemic sclerosis miners had significantly elevated frequencies in DRB10100 (DR1) and DRB1*0800 (D R8) only in comparison with unaffected miners and unexposed controls. Our genetic and immunological data lead to the assumption that a diffe rent set of HLA-D alleles in combination with exogenous factors is inv olved in the induction of anti-Scl-70 antibodies in uranium miners tha t might influence their susceptibility to the disease, whereas the sam e occupational exposure seems to have no influence on the induction of ACA antibodies.