A Potential Link Between <i>HLA‐DRB1/DQB1</i> Alleles and Response to Treatment in Rheumatoid Arthritis Patients

The present study aimed to determine the association of HLA-DRB1/-DQB1 alleles with response to treatment and anti-citrullinated peptide antibody (ACPA) status in Iranian rheumatoid arthritis (RA) patients. A total of 167 RA patients, including 114 good responders (GRs) and 53 poor responders (PRs) as well as 330 ethnic-matched healthy controls, participated in this study. Disease activity and treatment response were assessed using the Disease Activity Score 28-joint (DAS28) scores during the 9-month post-treatment. HLA-DRB1/-DQB1 alleles were identified using polymerase chain reaction with a sequence-specific primers (PCR-SSP) method and compared between the study groups. Of the patients, 106 (63.5%) were ACPA-positive, 88 (52.7%) human leucocyte antigen (HLA)-shared epitope (SE)-positive, 64 (38.3%) ACPA+SE+ and 37 (22.2%) ACPA-SE-. HLA-SE alleles were significantly more frequent in patients (p = 3.2e - 05), in PR versus GR patients (p = 0.01) and in ACPA+ versus ACPA- patients (p = 0.009). PR patients had a higher prevalence of ACPA+SE+ compared to GR patients (p = 0.02). Higher frequencies of DRB1*04:02 (p_c = 0.03), *04:04 (p_c = 0.007), *04:05 (p_c = 5.0e - 05), *10:01 (p_c = 1.0e - 04), DQB1*03:02 (p_c = 0.002) and *05:01 (p_c = 0.002) alleles, and lower frequencies of DRB1*04:01 (p_c = 0.007), *11:01 (p_c = 0.03), *13:01 (p_c = 0.03) and DQB1*06:03 (p_c = 0.03) alleles were observed in patients compared to healthy controls. These findings suggest a relationship between HLA-SE alleles and ACPA development and a potential link between HLA-SE/non-SE alleles and therapeutic responses in RA patients.