{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:00:28Z","timestamp":1780520428364,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008104","name":"Stichting Vrienden van de Voormalige te Noordwijk gevestigde Reumakliniek Sole Mio","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100008104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Autoantibody production is a hallmark of rheumatoid arthritis (RA). Anti-citrullinated protein antibodies (ACPA) are highly disease-specific, and their presence is associated with more severe disease and poor prognosis compared to ACPA-negative patients. However, the immune cell composition associated with antibody-positive\/negative disease is incompletely defined. Mass cytometry (MC) is a high-dimensional technique offering new possibilities in the determination of the immune cell composition in rheumatic diseases. Here, we set up a broad phenotyping panel to study the immune cell profile of early untreated RA to investigate if specific immune cell subsets are associated with ACPA+ versus ACPA\u2212 RA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Freshly obtained PBMCs of early, untreated RA patients (8 ACPA+ and 7 ACPA\u2212) were analysed using a 36-marker MC panel, including markers related to various immune lineages. Data were processed using Cytosplore for dimensional reduction (HSNE) and clustering. Groups were compared using Cytofast. A second validation cohort of cryopreserved PBMCs obtained from early RA patients (27 ACPA+ and 20 ACPA\u2212) was used to confirm MC data by flow cytometry (FC). FC data were processed and analysed using both an unsupervised analysis pipeline and through manual gating.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>MC indicated no differences when comparing major immune lineages (i.e. monocytes, T and B cells), but highlighted two innate subsets: CD62L<jats:sup>+<\/jats:sup> basophils (<jats:italic>p<\/jats:italic> = 0.33) and a subset of CD16<jats:sup>\u2212<\/jats:sup> NK cells (<jats:italic>p<\/jats:italic> = 0.063). Although the NK cell subset did not replicate by FC, FC replication confirmed the difference in CD62L<jats:sup>+<\/jats:sup> basophil frequency when comparing ACPA+ to ACPA\u2212 patients (mean 0.32% vs. 0.13%; <jats:italic>p<\/jats:italic> = 0.01).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Although no differences in major lineages were found between early ACPA+ and ACPA\u2212 RA, this study identified the reduced presence of activated basophils in ACPA-negative disease as compared to ACPA-positive disease and thereby provides the first evidence for a connection between activated basophils and ACPA status.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-021-02630-8","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T11:02:59Z","timestamp":1635505379000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Immunoprofiling of early, untreated rheumatoid arthritis using mass cytometry reveals an activated basophil subset inversely linked to ACPA status"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6046-9113","authenticated-orcid":false,"given":"H.","family":"Koppejan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hameetman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Beyrend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"van Unen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"Kwekkeboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H.","family":"van der Helm-van Mil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E. M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. A.","family":"van Gaalen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"2630_CR1","doi-asserted-by":"crossref","unstructured":"Fonseka CY, et al. Mixed-effects association of single cells identifies an expanded effector CD4+ T cell subset in rheumatoid arthritis. Sci. Transl. Med. 2018;10.\u00a0https:\/\/pubmed.ncbi.nlm.nih.gov\/30333237\/.","DOI":"10.1126\/scitranslmed.aaq0305"},{"key":"2630_CR2","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/nrrheum.2011.204","volume":"8","author":"A Willemze","year":"2012","unstructured":"Willemze A, Trouw LA, Toes REM, Huizinga TWJ. The influence of ACPA status and characteristics on the course of RA. Nat. Rev. Rheumatol. 2012;8:144\u201352.","journal-title":"Nat. Rev. Rheumatol."},{"key":"2630_CR3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003296","volume":"17","author":"XME Matthijssen","year":"2020","unstructured":"Matthijssen XME, Niemantsverdriet E, Huizinga TWJ, van der Helm-van Mil AHM. Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: a longitudinal cohort study in the Netherlands. 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All samples and data were coded to maintain the anonymity of the patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"HK has performed this work as part of her PhD studies and is currently an employee of Fluidigm. GB is currently an employee of VisuaLyte.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"272"}}