Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis

• Published in: Scientific reports Vol. 14; no. 1; p. 6763
• Main Authors: Cha, Soojin, Bang, So-Young, Joo, Young Bin, Cho, Soo-Kyung, Choi, Chan-Bum, Sung, Yoon-Kyoung, Kim, Tae-Hwan, Jun, Jae-Bum, Yoo, Dae Hyun, Lee, Hye-Soon, Bae, Sang-Cheol
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.03.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 692/4023/1670; 692/4023/1670/498; Abatacept; Amino acid; Amino acids; Drb1 protein; Epitopes; Haplotypes; Histocompatibility antigen HLA; HLA-DRB1; Humanities and Social Sciences; Inhibitors; multidisciplinary; Rheumatoid arthritis; Risk factors; Science; Science (multidisciplinary); Seropositive rheumatoid arthritis; Statistical analysis; TNF inhibitors; Treatment response; Valine; Seropositive rheumatoid arthritis; TNF inhibitors; Treatment response; Amino acid; Abatacept; HLA-DRB1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-56987-2

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P  = 0.067) and an inversely associated response to TNFi (OR 0.57, P  = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P  = 5.4 × 10 –3 ). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P  = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.