The Role of Shared Epitope in Rheumatoid Arthritis Prognosis in Relation to Anti-Citrullinated Protein Antibody Positivity

Abstract

Introduction: Shared epitope (SE) is present in high proportions of anti-citrullinated protein antibody (ACPA) ? patients with rheumatoid arthritis (RA) and is associated with poor prognosis. We assessed the role of SE in RA prognosis, in relation to ACPA positivity. Methods: Patients enrolled in the Brigham and Women's RA Sequential Study were included. Changes from baseline in disease activity (Disease Activity Score in 28 joints using C-reactive protein [DAS28 (CRP)], Clinical Disease Activity Index [CDAI], Simplified Disease Activity Index [SDAI]) to 1 year were assessed. Baseline characteristics were compared by SE and ACPA status (±; chi-squared, Kruskal-Wallis). Association between number of SE alleles and ACPA status (logistic regression models), relationships between baseline characteristics and changes in disease activity (adjusted linear regression model), and effect of ACPA on the association between SE and changes in disease activity (mediation analysis) were studied. Results: Nine hundred twenty-six patients were included. SE ? versus SEpatients had significantly longer disease duration and higher disease activity scores and were more likely to have erosive disease, have higher comorbidity burden, and be RF ? (all p \ 0.05). Among patients with one or two SE alleles (vs. 0), odds of being ACPA ? were 1.97 (p = 0.0003) and 3.82 (p \ 0.0001), respectively. SE ? versus SEpatients had worse disease activity scores as indicated by mean increases in DAS28 (CRP) of 0.22, CDAI of 2.07, and SDAI of 2.43 over 1 year (all p \ 0.05). Direct effect of SE ? accounted for 76.4-80.1% of total effect in disease activity increases. Conclusions: SE is strongly associated with ACPA positivity and higher disease activity in patients with RA. SE was associated with greater increases in disease activity over 1 year, which was partially mediated by the presence of ACPA.

Integrating Nanotechnological Advancements of Disease-Modifying Anti-Rheumatic Drugs into Rheumatoid Arthritis Management

“…The proximal interphalangeal, wrists, cervical spine, metatarsophalangeal, and metacarpophalangeal joints are recurrently affected joints in RA [ 4 ]. Various risk factors causing RA include smoking [ 5 ], menopause [ 6 ], hormonal disturbance [ 7 , 8 , 9 ], periodontal disease [ 10 , 11 , 12 ], and human leukocyte antigen (HLA), namely, HLA-DRB1 shared epitope alleles [ 13 , 14 ].…”

Comprehensive insights into rheumatoid arthritis: Pathophysiology, current therapies and herbal alternatives for effective disease management

“…The shared epitope (SE) of the HLA‐DR beta locus is a specific genetic determinant for the ACPA phenotype of RA (Larid et al, 2021; Wysocki et al, 2020). The peptide corresponding to the HLA/DR4/1 allele or the SE is responsible for presenting the autoantigen APC to T lymphocytes (Jung et al, 2022; Zhuo et al, 2022). The non‐HLA genes associated with RA are constituted by the peptidylarginine deiminase (PAD)‐I4, CD28 and LIMK1 (Mathebula et al, 2022).…”