Cross-reactivity of anti-modified protein antibodies in rheumatoid arthritis

Zhang G, Yao L, Zhu Q, Herrmann M, Zhao Y (2025)

Publication Type: Journal article, Review article

Publication year: 2025

Journal

Clinical and Experimental Rheumatology Clinical and Experimental Rheumatology Sas

Book Volume: 43

Pages Range: 1332-1344

Journal Issue: 7

DOI: 10.55563/clinexprheumatol/c0eeg7

Abstract

This review comprehensively discusses the cross-reactivity of autoantibodies against modified proteins (AMPAs), the hallmark of rheumatoid arthritis (RA). We found that regardless of tissue sources, subtypes, or isotypes of B cells, AMPAs show high cross-reactivity within and across antigens undergoing citrullination, carbamylation, lysine-acetylation or ornithine-acetylation. The cross-reactive patterns of AMPAs display clonal and individual heterogeneity. Variations in the antibody reactivity to different modified antigens in RA are due to the diverse cumulative effects of cross-reactive profiles of AMPA clones. 'Shared motifs', as short motifs composed of one core modified residue with one or two flanking amino acids, are essential for AMPA cross-reactivity. AMPAs likely undergo affinity maturation towards shared motifs, during which their cross-reactivity to citrullinated antigens was increased, so collaterally was their cross-reactivity to other modifications due to structural similarities between modified residues. Cross-reactivity could aid the activation of AMPA B cells by facilitating T-cell signals from various modified antigens, direct pathogenic effects to tissues where modified antigens accumulate, and drive the clearance of in vivo modified antigens.

Involved external institutions

West China Medical Center of Sichuan University / 四川大学华西医学中心 CN China (CN)

How to cite

APA:

Zhang, G., Yao, L., Zhu, Q., Herrmann, M., & Zhao, Y. (2025). Cross-reactivity of anti-modified protein antibodies in rheumatoid arthritis. Clinical and Experimental Rheumatology, 43(7), 1332-1344. https://doi.org/10.55563/clinexprheumatol/c0eeg7

MLA:

Zhang, Guangyue, et al. "Cross-reactivity of anti-modified protein antibodies in rheumatoid arthritis." Clinical and Experimental Rheumatology 43.7 (2025): 1332-1344.

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