{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:10:41Z","timestamp":1793686241139,"version":"4.5.1"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["2014\u20106824"],"award-info":[{"award-number":["2014\u20106824"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","award":["15\u20102\u2010310"],"award-info":[{"award-number":["15\u20102\u2010310"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"Objective<\/jats:title>Patients with Sj\u04e7gren's syndrome (SS<\/jats:styled-content>) have an increased risk of developing malignant B cell lymphomas, particularly mucosa\u2010associated lymphoid tissue (MALT<\/jats:styled-content>)\u2013type lymphomas. We have previously shown that a predominant proportion of patients with SS<\/jats:styled-content>\u2010associated salivary gland MALT<\/jats:styled-content> lymphoma express somatically hypermutated IgM with strong amino acid sequence homology with stereotypic rheumatoid factors (RF<\/jats:styled-content>s). The present study was undertaken in a larger cohort of patients with SS<\/jats:styled-content>\u2010associated MALT<\/jats:styled-content> lymphoma to more firmly assess the frequency of RF<\/jats:styled-content> reactivity and the significance of somatic IGV<\/jats:italic>\u2010region mutations for RF<\/jats:styled-content> reactivity.<\/jats:p><\/jats:sec>Methods<\/jats:title>B cell antigen receptors (BCR<\/jats:styled-content>s) of 16 patients with SS<\/jats:styled-content>\u2010associated salivary gland MALT<\/jats:styled-content> lymphoma were analyzed. Soluble recombinant IgM was produced of 12 MALT lymphoma samples, including 1 MALT<\/jats:styled-content> lymphoma sample that expressed an IgM antibody fitting in a novel IGHV<\/jats:styled-content>3\u201030<\/jats:italic>\u2013encoded stereotypic IGHV<\/jats:italic> subset. For 4 of the 12 IgM antibodies from MALT<\/jats:styled-content> lymphoma samples, the somatically mutated IGHV<\/jats:italic> and IGKV<\/jats:italic> gene sequences were reverted to germline configurations. Their RF<\/jats:styled-content> activity and binding affinity were determined by enzyme\u2010linked immunosorbent assay and surface plasmon resonance, respectively.<\/jats:p><\/jats:sec>Results<\/jats:title>Nine (75%) of the 12 IgM antibodies identified in patients with SS<\/jats:styled-content>\u2010associated salivary gland MALT<\/jats:styled-content> lymphoma displayed strong monoreactive RF<\/jats:styled-content> activity. Reversion of the IGHV<\/jats:italic> and IGKV<\/jats:italic> mutations to germline configuration resulted in RF<\/jats:styled-content> affinities for IgG that were significantly lower for 3 of the 4 somatically mutated IgM antibodies. In stereotypic IGHV<\/jats:styled-content>3\u20107<\/jats:italic>\/IGKV<\/jats:styled-content>3\u201015<\/jats:italic>\u2013encoded RF<\/jats:styled-content>s, a recurrent replacement mutation in the IGKV<\/jats:styled-content>3\u201015<\/jats:italic>\u2013third complementarity\u2010determining region was found to play a pivotal role in the affinity for IgG\u2010Fc.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>A majority of patients with SS\u2010associated salivary gland MALT lymphoma express somatically mutated BCRs that are selected for monoreactive, high\u2010affinity binding of IgG\u2010Fc. These data underscore the notion that soluble IgG, most likely in immune complexes in inflamed tissues, is the principal autoantigen in the pathogenesis of a variety of B cell lymphomas, particularly SS\u2010associated MALT lymphomas.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41263","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T13:16:23Z","timestamp":1584450983000},"page":"1330-1340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Salivary Gland Mucosa\u2010Associated Lymphoid Tissue\u2013Type Lymphoma From Sj\u00f6gren\u2019s Syndrome Patients in the Majority Express Rheumatoid Factors Affinity\u2010Selected for IgG"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-3138","authenticated-orcid":false,"given":"Richard J.","family":"Bende","sequence":"first","affiliation":[{"name":"Amsterdam University Medical Center and University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5855-4119","authenticated-orcid":false,"given":"Jerry","family":"Janssen","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center and University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0195-2823","authenticated-orcid":false,"given":"Anna","family":"Beentjes","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center and University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thera A. M.","family":"Wormhoudt","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center and University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-8250","authenticated-orcid":false,"given":"Koen","family":"Wagner","sequence":"additional","affiliation":[{"name":"AIMM Therapeutics Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlin A.","family":"Haacke","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen and University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G. M.","family":"Kroese","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen and University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6894-3441","authenticated-orcid":false,"given":"Jeroen E. J.","family":"Guikema","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center and University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7907-7390","authenticated-orcid":false,"given":"Carel J. M.","family":"van Noesel","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center and University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-624304"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.005983"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez052"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.08.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-119974"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.891439"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.110077"},{"key":"e_1_2_7_9_1","first-page":"977","article-title":"Rheumatoid factor and disease activity are independent predictors of lymphoma in primary Sj\u00f6gren's syndrome. 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