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*04:05:01, DRB1*10:01:01, DQB1*04:01:01, DPB1*02:01:02 and RA patients. Moreover, the haplotypes HLA-DRB1*04:05:01~ DQB1*04:01:01 and HLA-DRB1*10:01:01~ DQB1*05:01:01 were found to be more frequent in RA populations than in healthy controls. These possible susceptible HLA alleles (HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01 and DPB1*02:01:02) also showed higher frequencies in seropositive RA patients as compared to normal controls. The present study provided evidence that alleles HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01 and DPB1*02:01:02 constituted RA risk alleles, and haplotypes HLA-DRB1*04:05:01~ DQB1*04:01:01, HLA-DRB1*10:01:01~ DQB1*05:01:01 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.

KEYWORDS:

• Rheumatoid arthritis
• HLA class II alleles
• HLA-DRB1~DQB1 haplotypes
• autoantibodies

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request (https://www.ebi.ac.uk/ipd/imgt/hla/).

Declaration of interest

All the authors confirm that there are no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Ethics approval and consent to participate

This study was approved by the Institutes Ethics Committee (IEC) of University of Science and Technology of China (No.2019-N(H)-125), and all the participants signed the IEC-approved written informed consents.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [82001706], the Natural Science Foundation of Anhui Province [2008085QC155], and the Fundamental Research Funds for the Central Universities [WK9110000111].