MOLECULAR ANALYSIS OF HLA-DPB1 ALLELES IN IDIOPATHIC SYSTEMIC-SCLEROSIS PATIENTS AND URANIUM MINERS WITH SYSTEMIC-SCLEROSIS

According to clinical manifestation and autoantibody pattern [anti-Scl -70, anticentromere antibodies (ACAs)], systemic sclerosis is a connec tive tissue disease with heterogenous subgroups. PCR-sequence-specific -oligonucleotide typing was used to study the genetic association of H LA-DPB1 alleles in 54 patients with idiopathic systemic sclerosis, 26 uranium miners with systemic sclerosis and 70 unrelated healthy contro l subjects. Systemic sclerosis patients with and without former employ ment in mines were divided into two subgroups according to their scler oderma-typical autoantibody specificities -anti-Scl-70 positive and AC A positive - and a third subgroup comprising the rest. Statistical ana lysis revealed a significantly increased frequency of DPB11301 (p = 0 .0001, corrected p = 0.011) in idiopathic anti-Scl-70-positive systemi c sclerosis cases when compared with unexposed controls. In the same g roup, we observed an enhanced frequency of DPB10601 and *1701 alleles . Since these three alleles carry the information for a glutamic acid residue in position 69 of DPB1, we tested the association of this resi due with anti-Scl-70 expression. A strong association between anti-Scl -70 positivity in idiopathic systemic sclerosis patients and amino aci d residue 69 of DPB1 was observed when compared with anti-Scl-70-negat ive idiopathic systemic sclerosis patients (p=0.0009) or unrelated con trols (p = 0.0007). ACA expression was not associated with the presenc e of any DPB1 allele tested. The data show that anti-Scl-70 expression in idiopathic systemic sclerosis patients is linked with DPB11301 wh ereas anti-Scl-70-positive miners do not show such a DPB1 association. Furthermore, the data indicate that glutamate 69 of DPB1 might be inv olved in the susceptibility to idiopathic anti-Scl-70 expression.