Academic Journal
OP0003 AUTOREACTIVE CD4+ T CELLS AND THEIR TCR REPERTOIRE IN PR3-ANCA ASSOCIATED VASCULITIS
| العنوان: | OP0003 AUTOREACTIVE CD4+ T CELLS AND THEIR TCR REPERTOIRE IN PR3-ANCA ASSOCIATED VASCULITIS |
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| المؤلفون: | Kumar, R., Yoosuf, N., Bartoletti, A., Avik, A., Raposo, B., Jonasdottir, A., Lövström, B., Chemin, K., Bruchfeld, A., Gunnarsson, I., Malmström, V. |
| المصدر: | Annals of the Rheumatic Diseases ; volume 80, issue Suppl 1, page 1.3-1 ; ISSN 0003-4967 1468-2060 |
| بيانات النشر: | BMJ |
| سنة النشر: | 2021 |
| الوصف: | Background: ANCA-associated vasculitis (AAV) with proteinase 3 (PR3) ANCA is genetically associated with HLA-DP [1], is often relapsing in nature, and has a predisposition for kidneys, lungs and ear-nose-throat involvement [2]. Despite the presence of PR3+ANCA, indicating CD4+T-cell help in the disease, the knowledge about autoreactive CD4+T cells is scarce. Activated T cells have been shown at site of inflammation [3] and involvement of proinflammatory cytokines in circulation is also reported [4, 5]. Objectives: Identification of autoreactive T cells may help to identify the drivers of the immune responses and chronicity. We therefore aimed to investigate PR3-specific CD4+T-cell responses in peripheral blood of AAV patients with a focus on both phenotype and T-cell receptor (TCR) repertoires. Methods: The study included sixty-six patients: 26 with active PR3 autoantibody+ AAV, 21 with inactive but PR3+ AAV and 19 with inactive PR3- AAV. In-vitro cultures with PR3 protein were established to assess antigen-specific cytokine responses in a 3-color fluorospot assay. Deep immunophenotyping was performed by flow cytometry. Antigen-responsive CD4+ T cells were isolated and single cell TCRαβ sequences were generated and analyzed from PR3+ AAV patients (n=5) using a previously published protocol [6]. Results: PBMCs from AAV patients demonstrated an HLA-DP associated cytokine responses to PR3 stimulation including IFN-γ and IL-10, but not IL-17A. This T-cell autoreactivity was found to be confined to a highly differentiated CD4+ T cell population characterized by perforin and GPR56 expression, implicating a cytotoxic feature of the response. Active disease involved a reduction in expression of several markers associated with cytotoxicity amongst the CD4+GPR56+ T cells. Their frequency was also negatively associated with the doses of prednisolone. A similar phenotype was shared with T cells activated by human cytomegalovirus (HCMV) peptides in the same patient cohort. Single cell sequencing of paired alpha beta T-cell ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1136/annrheumdis-2021-eular.41 |
| الاتاحة: | http://dx.doi.org/10.1136/annrheumdis-2021-eular.41 https://syndication.highwire.org/content/doi/10.1136/annrheumdis-2021-eular.41 |
| رقم الانضمام: | edsbas.73874945 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/annrheumdis-2021-eular.41 |
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