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Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications.
- Source :
- Annals of the Rheumatic Diseases; Apr2020, Vol. 79 Issue 4, p472-480, 9p, 2 Black and White Photographs, 1 Diagram, 1 Chart, 2 Graphs
- Publication Year :
- 2020
-
Abstract
- <bold>Objective: </bold>Autoantibodies against antigens carrying distinct post-translational modifications (PTMs), such as citrulline, homocitrulline or acetyllysine, are hallmarks of rheumatoid arthritis (RA). The relation between these anti-modified protein antibody (AMPA)-classes is poorly understood as is the ability of different PTM-antigens to activate B-cell receptors (BCRs) directed against citrullinated proteins (CP). Insights into the nature of PTMs able to activate such B cells are pivotal to understand the 'evolution' of the autoimmune response conceivable underlying the disease. Here, we investigated the cross-reactivity of monoclonal AMPA and the ability of different types of PTM-antigens to activate CP-reactive BCRs.<bold>Methods: </bold>BCR sequences from B cells isolated using citrullinated or acetylated antigens were used to produce monoclonal antibodies (mAb) followed by a detailed analysis of their cross-reactivity towards PTM-antigens. Ramos B-cell transfectants expressing CP-reactive IgG BCRs were generated and their activation on stimulation with PTM-antigens investigated.<bold>Results: </bold>Most mAbs were highly cross-reactive towards multiple PTMs, while no reactivity was observed to the unmodified controls. B cells carrying CP-reactive BCRs showed activation on stimulation with various types of PTM-antigens.<bold>Conclusions: </bold>Our study illustrates that AMPA exhibit a high cross-reactivity towards at least two PTMs indicating that their recognition pattern is not confined to one type of modification. Furthermore, our data show that CP-reactive B cells are not only activated by citrullinated, but also by carbamylated and/or acetylated antigens. These data are vital for the understanding of the breach of B-cell tolerance against PTM-antigens and the possible contribution of these antigens to RA-pathogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00034967
- Volume :
- 79
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Annals of the Rheumatic Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 142482964
- Full Text :
- https://doi.org/10.1136/annrheumdis-2019-216499