{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:46:47Z","timestamp":1790776007213,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":681,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Zon-Mw Vidi","award":["91712334"],"award-info":[{"award-number":["91712334"]}]},{"DOI":"10.13039\/501100003246","name":"Investment Grant NWO Medium","doi-asserted-by":"publisher","award":["91116004"],"award-info":[{"award-number":["91116004"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["724517"],"award-info":[{"award-number":["724517"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Carbamylation is a post-translational modification that can be detected on a range of proteins, including immunoglobulin (Ig)G, in several clinical conditions. Carbamylated IgG (ca-IgG) was reported to lose its capacity to trigger complement activation, but the mechanism remains unclear. Because C1q binds with high affinity to hexameric IgG, we analyzed whether carbamylation of IgG affects binding of C1q, hexamerization and complement-dependent cytotoxicity (CDC). Synovial tissues of rheumatoid arthritis (RA) patients were analyzed for the presence of ca-IgG in vivo. Synovial tissues from RA patients were analyzed for the presence of ca-IgG using mass spectrometry (MS). Monomeric or hexameric antibodies were carbamylated in vitro and quality in solution was controlled. The capacity of ca-IgG to activate complement was analyzed in enzyme-linked immunosorbent (ELISAs) and cellular CDC assays. Using MS, we identified ca-IgG to be present in the joints of RA patients. Using in vitro carbamylated antibodies, we observed that ca-IgG lost its capacity to activate complement in both solid-phase and CDC assays. Mixing ca-IgG with non-modified IgG did not result in effective inhibition of complement activation by ca-IgG. Carbamylation of both monomeric IgG and preformed hexameric IgG greatly impaired the capacity to trigger complement activation. Furthermore, upon carbamylation, the preformed hexameric IgG dissociated into monomeric IgG in solution, indicating that carbamylation influences both hexamerization and C1q binding. In conclusion, ca-IgG can be detected in vivo and has a strongly reduced capacity to activate complement which is, in part, mediated through a reduced ability to form hexamers.<\/jats:p>","DOI":"10.1111\/cei.13411","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T08:13:03Z","timestamp":1576743183000},"page":"1-11","source":"Crossref","is-referenced-by-count":19,"title":["Carbamylation reduces the capacity of IgG for hexamerization and complement activation"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8661-4833","authenticated-orcid":false,"given":"R","family":"Lubbers","sequence":"first","affiliation":[{"name":"Department Rheumatology, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S C","family":"Oostindie","sequence":"additional","affiliation":[{"name":"Genmab , Utrecht, the Netherlands"},{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P W H I","family":"Parren","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands"},{"name":"Lava Therapeutics , Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M K","family":"Verheul","sequence":"additional","affiliation":[{"name":"Department Rheumatology, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Abendstein","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T H","family":"Sharp","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"de Ru","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G M C","family":"Janssen","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P A","family":"van Veelen","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E T J","family":"van den Bremer","sequence":"additional","affiliation":[{"name":"Genmab , Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Bleijlevens","sequence":"additional","affiliation":[{"name":"Genmab , Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B-J","family":"de Kreuk","sequence":"additional","affiliation":[{"name":"Genmab , Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F J","family":"Beurskens","sequence":"additional","affiliation":[{"name":"Genmab , Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-2290","authenticated-orcid":false,"given":"L A","family":"Trouw","sequence":"additional","affiliation":[{"name":"Department Rheumatology, Leiden University Medical Center , Leiden, the Netherlands"},{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,5]]},"reference":[{"key":"2023081612584406700_cei13411-bib-0001","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.immuni.2016.06.020","article-title":"Post-translational modification control of innate 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