MICA allele typing of HLA-B27 positive Japanese patients with seronegative spondylarthropathies and healthy individuals : Differential linkage disequilibrium with HLA-B27 subtypes

Objective To examine whether MICA (major histocompatibility complex [MHC] class I-related chain gene A) confers additional susceptibility for seronegative spondylarthropathies in HLA-B27 positive Japanese individuals. Methods A polymerase chain reaction-single-strand conformation polymorphism method was developed, and the MICA alleles of 18 Japanese patients with ankylosing spondylitis, 1 patient with Reiter's syndrome, and 17 healthy HLA-B27 positive Japanese subjects were determined. Results Among 26 individuals with HLA-B*2704 (13 patients and 13 healthy subjects), all except 1 healthy individual were positive for MICA010, whereas all 9 HLA-B*2705 positive subjects (6 patients and 3 healthy subjects) possessed MICA007. One healthy individual with HLA-B*2711 also carried MICA010. Conclusion Strong linkage disequilibrium is present between HLA-B*2704 and MICA010, as well as between HLA-B*2705 and MICA007. Although HLA-B*2704 and B*2705 are highly homologous, each subtype participates in a different MHC haplotype. Direct involvement of MICA polymorphism in the pathogenesis seems to be unlikely; however, such information will provide a useful tool for elucidating the evolutional pathway of HLA-B27 subtypes as well as the contribution of other genes within the MHC region in the pathogenesis of these diseases.