Molecular analysis of HLA-DPB1 alleles in idiopathic systemic sclerosis patients and uranium miners with systemic sclerosis.
According to clinical mainifestation and autoantibody pattern [anti-Scl-70, anti-centromere antibodies (ACAs)], systemic sclerosis is a connective tissue disease with heterogenous subgroups. PCR-sequence-specific-oligonucleotide typing was used to study the genetic association of HLA-DPB1 alleles in 54 patients with idiopathic systemic sclerosis, 26 uranium miners with systemic sclerosis and 70 unrelated healthy control subjects. Systemic sclerosis patients with and without former employment in mines were divided into two subgroups according to their scleroderma-typical autoantibody specificities--anti-Scl-70 positive and ACA positive--and third subgroup comprising the rest. Statistical analysis revealed a significantly increased frequency of DPB1*1301(p=0.0001, corrected p=0.011) in idiopathic anti-Scl-70-positive systemic sclerosis cases when compared with unexposed controls. In the same group, we observed an enhanced frequency of DPB1*0601 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 residue with anti-Scl-70 expression. A strong association between anti-Scl-70 positivity in idiopathic systemic sclerosis patients and amino acid residue 69 of DPB1 was observed when compared with anti-Scl-70-negative idiopathic systemic sclerosis patients (p=0.0009) or unrelated controls (p=0.0007). ACA expression was not associated with the presence of any DPB1 allele tested. The data show that anti-Scl-70 expression in idiopathic systemic sclerosis patients is linked with DPB1*1301 whereas anti-Scl-70-positive miners do not show such a DPB1 association. Futhermore, the data indicate that glutamate 69 of DPB1 might be involved in the susceptibility to idiopathic anti-Scl-70 expression.
Rihs
H P
HP
Abteilung Molekulare Genetik, Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA), Deutschland.
Conrad
K
K
Mehlhorn
J
J
May-Taube
K
K
Welticke
B
B
Frank
K H
KH
Baur
X
X
D000483:Alleles; D001483:Base Sequence; D005260:Female; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006801:Humans; D008297:Male; D008906:Mining; D008969:Molecular Sequence Data; D009784:Occupational Diseases / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D014501:Uranium / Q000009:adverse effects*
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D014501:Uranium