Influence of HLA Class II Alleles and DRB1-DQB1 Haplotypes on Rheumatoid Arthritis Susceptibility and Autoantibody Status in the Chinese Han Population.

ABSTRACT

Human leukocyte antigen (HLA) class II alleles are considered to play a key role in the progress of rheumatoid arthritis (RA). This study was carried out to investigate the presence of HLA class II alleles and their influence on disease risk and autoantibody status in Chinese Han patients with RA. Here, HLA-DRB1, DQB1 and DPB1 genotyping was performed in 125 RA patients and 120 healthy controls by using the next-generation sequencing (NGS). Strong positive associations were shown between high-resolution typed HLA-DRB1*040501, DRB1*100101, DQB1*040101, DPB1*020102 and RA patients. Moreover, the haplotypes HLA-DRB1*040501~ DQB1*040101 and HLA-DRB1*100101~ DQB1*050101 were found to be more frequent in RA populations than in healthy controls. These possible susceptible HLA alleles (HLA-DRB1*040501, DRB1*100101, DQB1*040101 and DPB1*020102) also showed higher frequencies in seropositive RA patients as compared to normal controls. The present study provided evidence that alleles HLA-DRB1*040501, DRB1*100101, DQB1*040101 and DPB1*020102 constituted RA risk alleles, and haplotypes HLA-DRB1*040501~ DQB1*040101, HLA-DRB1*100101~ DQB1*050101 also showed prevalence in Chinese Han patients with RA. Serological results preliminary demonstrated patients carrying RA-risk HLA alleles might elevate the serum level of anti-citrullinated protein antibodies and rheumatoid factor and affect RA progression.