Revisiting the Link Between HLA-DRB1 Alleles and Autoantibodies in Rheumatoid Arthritis: Association of Non-Shared Epitope Alleles 09 and 15 With High Levels of Anti-Citrullinated Peptide/Protein Antibodies

Overview

Journal ACR Open Rheumatol

Date 2024 Nov 22

PMID 39576054

Authors

Denis Lagutkin

Luis Panaifo

Ahmad-Fauzi Nurul-Aain

Lena Israelsson

Monika Hansson

Karin Lundberg

Lars Alfredsson

Johan Askling

Lars Klareskog

Chun-Lai Too

Leonid Padyukov

Affiliations

Soon will be listed here.

Abstract

Objective: Autoantibodies serve as essential clinical biomarkers and may indicate etiological mechanisms in rheumatic diseases. In light of the increasing knowledge concerning the diversity and biologic implications of anti-citrullinated peptide/protein antibodies (ACPAs), we have re-evaluated the association between the ACPA response and the HLA-DRB1 allelic groups, known to represent a major genetic risk factor for rheumatoid arthritis (RA).

Methods: We explored a collection of 4,392 well-characterized incident patients with RA of White European descent from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) new-onset RA study, as well as 1,199 cases of patients with RA of Southeast Asian origin from the Malaysian EIRA study. We focused on a quantitative analysis of the levels of anti-cyclic citrullinated peptide IgG antibodies, including those falling below the diagnostic threshold.

Results: Our data show that non-shared epitope alleles HLA-DRB1*09 and *15 exhibit significant associations with ACPA levels. Notably, these novel associations were independent of ethnicity. To validate our findings, we conducted an additional replication study in an independent pool of 4,109 patients with RA of White European origin.

Conclusion: These results indicate a new, previously overlooked, role for the HLA locus in the regulation of the levels of ACPA RA-specific autoantibodies that goes beyond the shared epitope-defined gene variants.

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Revisiting the Link Between HLA-DRB1 Alleles and Autoantibodies in Rheumatoid Arthritis: Association of Non-Shared Epitope Alleles *09 and *15 With High Levels of Anti-Citrullinated Peptide/Protein Antibodies

Revisiting the Link Between HLA-DRB1 Alleles and Autoantibodies in Rheumatoid Arthritis: Association of Non-Shared Epitope Alleles 09 and 15 With High Levels of Anti-Citrullinated Peptide/Protein Antibodies