Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment response in rheumatoid arthritis
| Autor: | Hannes Uchtenhagen, Anca I. Catrina, Sara Turcinov, William W. Kwok, TH Ramwadhdoebe, Genadiy Kozhukh, Aase Haj Hensvold, Anatoly Dubnovitsky, Karine Chemin, Lisa G. M. van Baarsen, Vivianne Malmström, Adnane Achour, Lars Rönnblom, Christina Gerstner |
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| Přispěvatelé: | Graduate School, 01 Internal and external specialisms, AII - Inflammatory diseases, AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Male lcsh:Immunologic diseases. Allergy Autoreactive CD4+ T lymphocytes Immunology Epitopes T-Lymphocyte Flow cytometry Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine Antigen Autoimmune disease medicine Humans Vimentin Pyrophosphatases Aged 030203 arthritis & rheumatology Extracellular Matrix Proteins medicine.diagnostic_test business.industry Histocompatibility Antigens Class II Citrullination Fibrinogen Immunology in the medical area Autoreactive CD4+T lymphocytes Middle Aged medicine.disease Flow Cytometry Multi-MHC class II tetramer assay 3. Good health 030104 developmental biology Lymphatic system Rheumatoid arthritis Immunologi inom det medicinska området Citrulline Female business lcsh:RC581-607 Ex vivo Blood drawing Research Article |
| Zdroj: | BMC Immunology, Vol 21, Iss 1, Pp 1-14 (2020) BMC Immunology BMC immunology, 21(1):27. BioMed Central |
| ISSN: | 1471-2172 |
| Popis: | Background HLA class II tetramers can be used for ex vivo enumeration and phenotypic characterisation of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disorder for which many autoantigens have been described. Results Using multi-parameter flow cytometry, we developed a multi-HLA class II tetramer approach to simultaneously study several antigen specificities in RA patient samples. We focused on previously described citrullinated HLA-DRB1*04:01-restricted T cell epitopes from α-enolase, fibrinogen-β, vimentin as well as cartilage intermediate layer protein (CILP). First, we examined inter-assay variability and the sensitivity of the assay in peripheral blood from healthy donors (n = 7). Next, we confirmed the robustness and sensitivity in a cohort of RA patients with repeat blood draws (n = 14). We then applied our method in two different settings. We assessed lymphoid tissue from seropositive arthralgia (n = 5) and early RA patients (n = 5) and could demonstrate autoreactive T cells in individuals at risk of developing RA. Lastly, we studied peripheral blood from early RA patients (n = 10) and found that the group of patients achieving minimum disease activity (DAS28 Conclusions Our study demonstrates the development of a sensitive tetramer panel allowing simultaneous characterisation of antigen-specific T cells in ex vivo patient samples including RA ‘at risk’ subjects. This multi-tetramer approach can be useful for longitudinal immune-monitoring in any disease with known HLA-restriction element and several candidate antigens. |
| Databáze: | OpenAIRE |
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