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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 \u03b1-enolase, fibrinogen-\u03b2, 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                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097). Next, we confirmed the robustness and sensitivity in a cohort of RA patients with repeat blood draws (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914). We then applied our method in two different settings. We assessed lymphoid tissue from seropositive arthralgia (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) and early RA patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) and could demonstrate autoreactive T cells in individuals at risk of developing RA. Lastly, we studied peripheral blood from early RA patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) and found that the group of patients achieving minimum disease activity (DAS28\u2009&lt;\u20092.6) at 6\u2009months follow-up displayed a decrease in the frequency of citrulline-specific T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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 \u2018at risk\u2019 subjects. This multi-tetramer approach can be useful for longitudinal immune-monitoring in any disease with known HLA-restriction element and several candidate antigens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12865-020-00357-w","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T16:11:33Z","timestamp":1589818293000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment response in rheumatoid arthritis"],"prefix":"10.1186","volume":"21","author":[{"given":"Christina","family":"Gerstner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Turcinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aase H.","family":"Hensvold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Chemin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Uchtenhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara H.","family":"Ramwadhdoebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly","family":"Dubnovitsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genadiy","family":"Kozhukh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"R\u00f6nnblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnane","family":"Achour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca I.","family":"Catrina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa G. 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