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.
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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ACR Meeting Abstracts - https://acrabstracts.org/abstract/divergent-reactivities-of-rheumatoid-factors-and-anti-modified-protein-antibodies-converge-on-igg-epitopes/