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Herein, we demonstrate the frequency of variable\u2010region glycosylation in single\u2010cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N\u2010linked glycosylation motifs <jats:italic>in silico<\/jats:italic>, and compared to 452 highly\u2010mutated mAbs from RA patients and controls. Variable region N\u2010linked motifs (N\u2010X\u2010S\/T) were strikingly prevalent within ACPA (100%) compared to somatically hypermutated (SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from seropositive (39%) and seronegative RA (7%). When normalized for SHM, ACPA still had significantly higher frequency of N\u2010linked motifs compared to all studied mAbs including highly mutated HIV broadly\u2010neutralizing and malaria\u2010associated mAbs. The Fab glycans of ACPA\u2010mAbs were highly sialylated, contributed to altered charge, but did not influence antigen binding. The analysis revealed evidence of unusual B\u2010cell selection pressure and SHM\u2010mediated decrease in surface charge and isoelectric point in ACPA. It is still unknown how these distinct features of anti\u2010citrulline immunity may have an impact on pathogenesis. However, it is evident that they offer selective advantages for ACPA<jats:sup>+<\/jats:sup> B cells, possibly through non\u2010antigen driven mechanisms.<\/jats:p>","DOI":"10.1002\/eji.201747446","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T11:22:42Z","timestamp":1520421762000},"page":"1030-1045","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Variable domain N\u2010linked glycosylation and negative surface charge are key features of monoclonal ACPA: Implications for B\u2010cell selection"],"prefix":"10.1002","volume":"48","author":[{"given":"Katy A.","family":"Lloyd","sequence":"first","affiliation":[{"name":"Department of Medicine Rheumatology Unit Karolinska Institutet Karolinska University Hospital Center for Molecular Medicine  Stockholm 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Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Medicine Rheumatology Unit Karolinska Institutet Karolinska University Hospital Center for Molecular Medicine  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Piccoli","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine Universit\u00e0 della Svizzera italiana  Bellinzona Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Gabay","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University Hospitals of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Lanzavecchia","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine Universit\u00e0 della Svizzera italiana  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