{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:50:22Z","timestamp":1777539022514,"version":"3.51.4"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","award":["17-1-402 and 08-1-34"],"award-info":[{"award-number":["17-1-402 and 08-1-34"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RTCure","award":["777357"],"award-info":[{"award-number":["777357"]}]},{"name":"Target to B!","award":["LSHM18055-5GF"],"award-info":[{"award-number":["LSHM18055-5GF"]}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["AdG2019-884796"],"award-info":[{"award-number":["AdG2019-884796"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute for Chemical Immunology","award":["NWO-024.002.009"],"award-info":[{"award-number":["NWO-024.002.009"]}]},{"name":"NWO-ZonMW VIDI","award":["09150172010067"],"award-info":[{"award-number":["09150172010067"]}]},{"name":"NWO-ZonMW OffRoad","award":["451001012"],"award-info":[{"award-number":["451001012"]}]},{"DOI":"10.13039\/501100022115","name":"Dutch Arthritis Association","doi-asserted-by":"publisher","award":["15-2-402 and 18-1-205"],"award-info":[{"award-number":["15-2-402 and 18-1-205"]}],"id":[{"id":"10.13039\/501100022115","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>Rheumatoid arthritis (RA) is characterized by the presence of disease-specific autoreactive B cell responses, in particular those generating anti-citrullinated protein antibodies (ACPA). For many years, Epstein-Barr virus (EBV) has been implicated in disease pathogenesis, possibly by facilitating the development and persistence of autoreactive B cells. To test this hypothesis, the presence of EBV episomes in ACPA-expressing B cells was analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>ACPA-expressing B cells derived from peripheral blood (PB) of seven EBV-seropositive RA patients, and synovial fluid (SF) of one additional EBV-seropositive RA patient, were isolated by flow cytometry. PB cells were expanded for 11\u201312 days, after which supernatant was harvested and analyzed for cyclic citrullinated-peptide (CCP)2 reactivity. SF cells were isolated directly in a lysis buffer. DNA was isolated and qPCR reactions were performed to determine the EBV status of the cells. EBV-immortalized B cell lymphoblastoid-cell lines (EBV blasts) served as standardized controls.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Two hundred ninety-six PB and 60 SF ACPA-expressing B cells were isolated and divided over 16 and 3 pools containing 10\u201320 cells, respectively. Supernatants of all 16 cultured PB pools contained CCP2-Ig. DNA of all pools was used for qPCR analysis. While EBV-blast analysis showed sensitivity to detect EBV DNA in single B cells, no EBV DNA was detected in any of the ACPA-expressing B cell pools.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>ACPA-expressing B cells are not enriched for EBV-DNA-containing clones. These results do not support the hypothesis that EBV infection of autoreactive B cells causes or maintains autoreactive B cell populations in RA. Instead, other mechanisms might explain the association between positive EBV serology and RA.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-022-02919-2","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T09:02:54Z","timestamp":1665651774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Absence of Epstein-Barr virus DNA in anti-citrullinated protein antibody-expressing B cells of patients with rheumatoid arthritis"],"prefix":"10.1186","volume":"24","author":[{"given":"Sanne","family":"Kroos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arieke S. B.","family":"Kampstra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9 E. M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda M.","family":"Slot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans U.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"2919_CR1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41584-022-00786-4","volume":"18","author":"HU Scherer","year":"2022","unstructured":"Scherer HU, van der Woude D, Toes REM. From risk to chronicity: evolution of autoreactive B cell and antibody responses in rheumatoid arthritis. Nat Rev Rheumatol. 2022;18:371.","journal-title":"Nat Rev Rheumatol"},{"key":"2919_CR2","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3389\/fonc.2018.00211","volume":"8","author":"MK Smatti","year":"2018","unstructured":"Smatti MK, Al-Sadeq DW, Ali NH, Pintus G, Abou-Saleh H, Nasrallah GK. Epstein-Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update. Front Oncol. 2018;8:211.","journal-title":"Front Oncol"},{"key":"2919_CR3","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/S1074-7613(02)00318-7","volume":"16","author":"LL Laichalk","year":"2002","unstructured":"Laichalk LL, Hochberg D, Babcock GJ, Freeman RB, Thorley-Lawson DA. The Dispersal of Mucosal Memory B Cells: Evidence from Persistent EBV Infection. Immunity. 2002;16:745\u201354.","journal-title":"Immunity."},{"issue":"2","key":"2919_CR4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.jbspin.2017.04.011","volume":"85","author":"N Balandraud","year":"2018","unstructured":"Balandraud N, Roudier J. Epstein-Barr virus and rheumatoid arthritis. Joint Bone Spine. 2018;85(2):165\u201370.","journal-title":"Joint Bone Spine"},{"issue":"5","key":"2919_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.it.2007.03.002","volume":"28","author":"M Swanson-Mungerson","year":"2007","unstructured":"Swanson-Mungerson M, Longnecker R. Epstein-Barr virus latent membrane protein 2A and autoimmunity. Trends Immunol. 2007;28(5):213\u20138.","journal-title":"Trends Immunol"},{"issue":"10","key":"2919_CR6","doi-asserted-by":"publisher","first-page":"5215","DOI":"10.4049\/jimmunol.171.10.5215","volume":"171","author":"B He","year":"2003","unstructured":"He B, Raab-Traub N, Casali P, Cerutti A. 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All donors gave written informed consent.","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":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"230"}}