Rheumatoid Factor and Anti-Modified Protein Antibody Reactivities Converge on IgG Epitopes.

Autor: Mergaert AM; University of Wisconsin-Madison., Zheng Z; University of Wisconsin-Madison., Denny MF; University of Wisconsin-Madison., Amjadi MF; University of Wisconsin-Madison., Bashar SJ; University of Wisconsin-Madison., Newton MA; University of Wisconsin-Madison., Malmström V; Karolinska University Hospital, Stockholm, Sweden., Grönwall C; Karolinska University Hospital, Stockholm, Sweden., McCoy SS; University of Wisconsin-Madison., Shelef MA; University of Wisconsin-Madison and William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2022 Jun; Vol. 74 (6), pp. 984-991. Date of Electronic Publication: 2022 Apr 10.
DOI: 10.1002/art.42064
Abstrakt: Objective: Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive 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. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG.
Methods: Using sera from patients with RA, systemic lupus erythematosus, Sjögren's disease (SjD), or spondyloarthropathy, IgG binding to native, citrulline-containing, and homocitrulline-containing linear epitopes of the IgG constant region was evaluated by peptide array, with highly bound epitopes further evaluated by enzyme-linked immunosorbent assay (ELISA). Binding of monoclonal AMPAs to IgG-derived peptides and IgG Fc was also evaluated by ELISA.
Results: Seropositive RA sera showed high IgG binding to multiple citrulline- and homocitrulline-containing IgG-derived peptides, whereas anti-SSA+ sera from SjD patients showed consistent binding to a single linear native epitope of IgG in the hinge region. Monoclonal 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 otherwise divergent reactivities of RFs and AMPAs.
(© 2022 American College of Rheumatology.)
Databáze: MEDLINE
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