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Abstract Number: 0007

Divergent Reactivities of Rheumatoid Factors and Anti-Modified Protein Antibodies Converge on IgG Epitopes

Aisha Mergaert1, Zihao Zheng1, Michael Denny1, Maya Amjadi1, Janna Bashar1, Michael Newton1, Vivianne Malmström2, Caroline Grönwall2, Sara McCoy1 and Miriam Shelef1, 1University of Wisconsin, Madison, WI, 2Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

Meeting: ACR Convergence 2021

Keywords: Anti-citrullinated Protein Autoantibodies (ACPAs), rheumatoid arthritis, Rheumatoid Factor

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Session Information

Date: Saturday, November 6, 2021

Session Title: B Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster (0001–0010)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multi-reactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline-containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. The objective of this study was to reveal new IgG epitopes in rheumatic disease and to determine if cross-reactive AMPAs bind IgG.

Methods: Using RA, lupus, Sjögren’s syndrome, and spondyloarthropathy sera, IgG binding to native, citrulline-containing, and homocitrulline-containing linear epitopes of the IgG constant region were evaluated by peptide array with novel epitopes further evaluated by ELISA. Monoclonal AMPA binding to IgG-derived peptides and IgG Fc was evaluated by ELISA.

Results: Seropositive RA sera had high IgG binding to multiple citrulline- and homocitrulline-containing IgG-derived peptides, whereas only anti-SSA+ Sjögren’s Syndrome had consistent binding to a single linear native epitope of IgG. AMPAs bound citrulline- and homocitrulline-containing IgG peptides and modified IgG Fc.

Conclusion: The repertoire of epitopes bound by AMPAs includes modified IgG epitopes, positioning IgG as a common antigen that connects the divergent reactivities of RFs and AMPAs.


Disclosures: A. Mergaert, None; Z. Zheng, None; M. Denny, None; M. Amjadi, None; J. Bashar, None; M. Newton, None; V. Malmström, None; C. Grönwall, None; S. McCoy, BMS, 2, Novartis, 1, Boehringer Ingelheim, 6; M. Shelef, None.

To cite this abstract in AMA style:

Mergaert A, Zheng Z, Denny M, Amjadi M, Bashar J, Newton M, Malmström V, Grönwall C, McCoy S, Shelef M. Divergent Reactivities of Rheumatoid Factors and Anti-Modified Protein Antibodies Converge on IgG Epitopes [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/divergent-reactivities-of-rheumatoid-factors-and-anti-modified-protein-antibodies-converge-on-igg-epitopes/. Accessed January 27, 2023.
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