抗瓜氨酸抗体识别细菌L-天冬酰胺酶修饰的类风湿性关节炎相关T细胞表位。

IF 1.5 4区 医学 Q4 IMMUNOLOGY Central European Journal of Immunology Pub Date : 2023-01-01 Epub Date: 2023-09-21 DOI:10.5114/ceji.2023.131455
Tsvetelina Batsalova, Ivanka Teneva, Krum Bardarov, Dzhemal Moten, Balik Dzhambazov
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引用次数: 0

摘要

瓜氨酸蛋白和抗瓜氨酸蛋白抗体(ACPAs)在类风湿性关节炎(RA)的发病机制中起着重要作用。有人认为,在炎症或微生态失调期间,细菌可以启动ACPA的产生。大多数RA患者对ACPA呈血清阳性,但这些抗体对不同的翻译后修饰(PTM)具有重叠反应性。对于RA的起始和发展,仍然需要T淋巴细胞和T细胞表位。在本研究中,我们评估了细菌L-天冬酰胺酶修饰II型胶原内RA相关T细胞表位(CII259-273和CII311-325)的能力,以及这些修饰的表位是否被RA患者的ACPA识别。我们纳入了12名早期RA患者和11名根据预定义的特定标准选择的健康受试者。LC-MS/MS分析表明,细菌L-天冬酰胺酶可以修饰所研究的T细胞表位。ELISA测试显示,早期RA患者的ACPA阳性血清对II型胶原(CII)内酶修饰的免疫显性T细胞表位具有交叉反应性,但对修饰的无关肽没有交叉反应性。这些数据表明,交叉反应的ACPA识别CII中的“羰基Gly-Pro”基序。此外,T细胞对修饰的主要免疫显性T细胞表位Gal264-CII259-273的识别没有受到影响。该表位仍然能够激活早期RA患者的自身反应性T细胞。这种修饰很可能是T细胞启动和抗修饰蛋白抗体(AMPA)开发之间缺失的环节。我们的研究结果为RA的病因和发病机制提供了更多的信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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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, 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.

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来源期刊
CiteScore
3.00
自引率
0.00%
发文量
17
审稿时长
6-12 weeks
期刊介绍: Central European Journal of Immunology is a English-language quarterly aimed mainly at immunologists.
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