{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T17:53:13Z","timestamp":1775929993964,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Primary cold agglutinin disease (CAD) is a monoclonal antibody (M\u2010protein) and complement\u2010mediated chronic hemolytic disease process. Antibody glycosylation can play a role in both antibody half\u2010life and complement fixation. Recently, M\u2010protein light chain (LC) glycosylation has been shown to be associated with AL amyloidosis. We hypothesized that M\u2010protein LC glycosylation is also associated with cold agglutinin (CA) titers and CA\u2010mediated hemolysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>A cross\u2010sectional study of patients undergoing CA titer evaluation underwent mass spectrometric analysis for M\u2010proteins and M\u2010protein LC glycosylation. A subset of serum samples also underwent evaluation for the ability to trigger cold hemolysis in vitro. M\u2010protein and M\u2010protein LC glycosylation rates were compared across CA titer groups, clinical diagnosis, direct antiglobulin testing (DAT) results, and cold in vitro hemolysis rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both M\u2010protein and M\u2010protein LC glycosylation rates significantly differed across CA titer groups with the highest rates in those with elevated CA titers. M\u2010protein LC glycosylation occurred almost exclusively on IgM kappa M\u2010proteins and was significantly associated with positive DAT results and a clinical diagnosis of CAD. Cold in vitro hemolysis was demonstrated in two patients who both had a CA titer of more than 512 but there was no significant association with CA titer group or M\u2010protein LC glycosylation status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>M\u2010protein LC glycosylation is significantly associated with higher CA titer levels. Given the role that antibody glycosylation can play in antibody half\u2010life and complement fixation, further studies are needed to clarify the effects of LC glycosylation within the context of CAD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.16279","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T13:29:28Z","timestamp":1611754168000},"page":"1302-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In from the cold: M\u2010protein light chain glycosylation is positively associated with cold agglutinin titer levels"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7868-2852","authenticated-orcid":false,"given":"Justin E.","family":"Juskewitch","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine &amp; Pathology Mayo Clinic  Rochester 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