eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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vol. 48
Experimental immunology

Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase

Tsvetelina Batsalova
Ivanka Teneva
Krum Bardarov
Dzhemal Moten
Balik Dzhambazov

Faculty of Biology, Paisii Hilendarski University of Plovdiv, Plovdiv, Bulgaria
InoBioTech Ltd, Sofia, Bulgaria
Cent Eur J Immunol 2023; 48 (3): 174-188
Online publish date: 2023/09/21
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Citrullinated proteins and anti-citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). It has been suggested that during inflammation or dysbiosis, bacteria could initiate production of ACPAs. Most patients with RA are seropositive for ACPAs, but these antibodies have overlapping reactivity to different posttranslational modifications (PTMs). For initiation and development of RA, T lymphocytes and T cell epitopes are still required. In this study, we evaluated the ability of bacterial L-asparaginase to modify RA-related T cell epitopes within type II collagen (CII259-273 and CII311-325), as well as whether these modified epitopes are recognized by ACPAs from RA patients. We included 12 patients with early RA and 11 healthy subjects selected according to predefined specific criteria. LC-MS/MS analyses revealed that the bacterial L-asparaginase can modify investigated T cell epitopes. ELISA tests showed cross-reactivity of ACPA positive sera from early RA patients towards the enzymatically modified immunodominant T cell epitopes within type II collagen (CII), but not to the modified irrelevant peptides. These data suggest that the cross-reactive ACPAs recognize the “carbonyl-Gly-Pro” motif in CII. Moreover, the T cell recognition of the modified major immunodominant T cell epitope Gal264-CII259-273 was not affected. This epitope was still able to activate autoreactive T cells from early RA patients. It is likely that such modifications are the missing link between the T cell priming and the development of anti-modified protein antibodies (AMPAs). Our results provide additional information on the etiology and pathogenesis of RA.

rheumatoid arthritis, pathogenesis, L-asparaginase, type II collagen, T-cell epitopes, posttranslational modifications, anti-citrullinated protein antibodies (ACPAs)

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