HLA CLASS-II GENES ASSOCIATED WITH ANTICENTROMERE ANTIBODY IN JAPANESE PATIENTS WITH SYSTEMIC-SCLEROSIS (SCLERODERMA)

Objective-To define further HLA class II gene associations with anticentromere antibody (ACA), a major serum antinuclear antibody in patients with systemic sclerosis (SSc). Methods-HLA class II genes were determined using polymerase chain reaction/ restriction fragment length polymorphisms in 94 Japanese patients with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control subjects. Results-Frequency of DQB1*0501 was increased in ACA positive SSc patients compared with ACA negative SSc patients (36% versus 13%; p = 0.02, odds ratio = 4.0, 95% confidence interval 1.1 to 13.9), but the association of ACA with a polar amino acid at position 26 in the DQB1 pi domain, which was demonstrated in white North Americans, was not observed in Japanese. The DRB1*0101, *0405, and *1302 alleles were associated with high ACA titres, whereas DRB1*1502 was associated with low ACA titres and a low frequency of centromere protein C (CENP-C) reactivity. Conclusions-These results suggest that the ACA response is associated with multiple HLA class II genes and that ACA positive SSc patients are heterogeneous in terms of immunogenetic background.