Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase
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...
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| Format: | Article |
| Language: | English |
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Termedia Publishing House
2023-09-01
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| Series: | Central European Journal of Immunology |
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| Online Access: | https://www.termedia.pl/Anticitrullinated-antibodies-recognize-rheumatoid-arthritis-associated-T-cell-epitopes-modified-by-bacterial-L-asparaginase,10,51466,1,1.html |
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| author | Tsvetelina Batsalova Ivanka Teneva Krum Bardarov Dzhemal Moten Balik Dzhambazov |
| author_facet | Tsvetelina Batsalova Ivanka Teneva Krum Bardarov Dzhemal Moten Balik Dzhambazov |
| author_sort | Tsvetelina Batsalova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T14:43:09Z |
| format | Article |
| id | doaj.art-13c2790433ab414eac3557c3d879cb6a |
| institution | Directory Open Access Journal |
| issn | 1426-3912 1644-4124 |
| language | English |
| last_indexed | 2024-03-09T14:43:09Z |
| publishDate | 2023-09-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Central European Journal of Immunology |
| spelling | doaj.art-13c2790433ab414eac3557c3d879cb6a2023-11-27T12:09:53ZengTermedia Publishing HouseCentral European Journal of Immunology1426-39121644-41242023-09-0148317418810.5114/ceji.2023.13145551466Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginaseTsvetelina BatsalovaIvanka TenevaKrum BardarovDzhemal MotenBalik DzhambazovCitrullinated 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.https://www.termedia.pl/Anticitrullinated-antibodies-recognize-rheumatoid-arthritis-associated-T-cell-epitopes-modified-by-bacterial-L-asparaginase,10,51466,1,1.htmlrheumatoid arthritis pathogenesis l-asparaginase type ii collagen t-cell epitopes posttranslational modifications anti-citrullinated protein antibodies (acpas) |
| spellingShingle | Tsvetelina Batsalova Ivanka Teneva Krum Bardarov Dzhemal Moten Balik Dzhambazov Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase Central European Journal of Immunology rheumatoid arthritis pathogenesis l-asparaginase type ii collagen t-cell epitopes posttranslational modifications anti-citrullinated protein antibodies (acpas) |
| title | Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase |
| title_full | Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase |
| title_fullStr | Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase |
| title_full_unstemmed | Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase |
| title_short | Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase |
| title_sort | anticitrullinated antibodies recognize rheumatoid arthritis associated t cell epitopes modified by bacterial l asparaginase |
| topic | rheumatoid arthritis pathogenesis l-asparaginase type ii collagen t-cell epitopes posttranslational modifications anti-citrullinated protein antibodies (acpas) |
| url | https://www.termedia.pl/Anticitrullinated-antibodies-recognize-rheumatoid-arthritis-associated-T-cell-epitopes-modified-by-bacterial-L-asparaginase,10,51466,1,1.html |
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