Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications
| Autor: | M. Reth, E W N Levarht, Hans Scherer, J.C. Kwekkeboom, J. W. Drijfhout, Holger Bang, Sanne Reijm, Gerrie Stoeken-Rijsbergen, Arieke S. B. Kampstra, George M.C. Janssen, P.A. van Veelen, Marco Cavallari, Corrie M. Wortel, Rem Toes, Twj Huizinga, Theresa Kissel, Rochelle D Vergroesen, Kimberly M. Bonger, Linda M. Slot |
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| Přispěvatelé: | Academic Medical Center |
| Rok vydání: | 2020 |
| Předmět: |
Male
rheumatoid arthritis 0301 basic medicine autoantibodies medicine.drug_class Immunology Receptors Antigen B-Cell Synthetic Organic Chemistry Cross Reactions medicine.disease_cause Monoclonal antibody Cross-reactivity Anti-Citrullinated Protein Antibodies General Biochemistry Genetics and Molecular Biology Arthritis Rheumatoid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Rheumatology Antigen medicine Humans Immunology and Allergy Receptor Aged 030203 arthritis & rheumatology B-Lymphocytes B cells Protein Carbamylation biology business.industry Autoantibody Acetylation Middle Aged 3. Good health Cell biology 030104 developmental biology chemistry Immunoglobulin G Acetyllysine Monoclonal biology.protein Citrulline Citrullination Female Antibody business Protein Processing Post-Translational |
| Zdroj: | Annals of the rheumatic diseases, 79(4):216499, 472-480. BMJ Publishing Group Annals of the Rheumatic Diseases, 79, 472-480 Annals of the Rheumatic Diseases, 79, 4, pp. 472-480 Annals of the Rheumatic Diseases, 79(4), 472-480. BMJ PUBLISHING GROUP Annals of the rheumatic disease |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | ObjectiveAutoantibodies 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.MethodsBCR 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.ResultsMost 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.ConclusionsOur 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. |
| Databáze: | OpenAIRE |
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