{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:51:01Z","timestamp":1791460261360,"version":"4.3.4"},"reference-count":16,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Therapeutic monoclonal antibodies, widely used in multiple myeloma (MM), can interfere with the interpretation of serum protein electrophoresis (SPEP) and immunofixation electrophoresis results, challenging the differentiation from endogenous monoclonal (M) proteins associated with the disease. Although this interference has been well established for several therapeutic monoclonal antibodies, the potential impact of denosumab, an IgG2(\u03ba) antibody used to treat MM-related bone disease, remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We characterized the electrophoretic migration of denosumab using in vitro spiking experiments. To evaluate in vivo interference, we performed a retrospective review of SPEP and immunotyping results from 110 patients with MM receiving denosumab. Finally, we used matrix-assisted desorption\/ionization time-of-flight mass spectrometry (using the EXENT system) to distinguish between denosumab and endogenous M-proteins based on molecular mass.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro, denosumab migrated to the mid-to-distal gamma region, nearer the cathodal end than daratumumab, with a normalized migration ratio of approximately 1.34. Among the 110 patients, one exhibited a corresponding IgG(\u03ba) peak on SPEP and immunotyping with the specified migration position, although mass spectrometry confirmed this to be an endogenous M-protein rather than denosumab. No denosumab-specific interference was detected above the lower limit of quantification (15\u2005mg\/L) using mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although denosumab exhibited a consistent electrophoretic migration pattern in vitro, it did not cause clinically relevant in vivo interference in SPEP or immunotyping assays. These findings support accurate electrophoretic interpretation and reduce concerns regarding misclassification of M-proteins in patients with MM receiving denosumab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jalm\/jfag135","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:56:19Z","timestamp":1790769379000},"source":"Crossref","is-referenced-by-count":0,"title":["Investigating Denosumab Interference in Serum Protein Electrophoresis"],"prefix":"10.1093","author":[{"given":"Sungyu","family":"Jee","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, the Catholic University of Korea , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungjun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, the Catholic University of Korea , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwool","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, St. Vincent\u2019s Hospital, College of Medicine, the Catholic University of Korea , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyojin","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, the Catholic University of Korea , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"2026100807000252400_jfag135-B1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1373\/jalm.2019.029009","article-title":"Incidence and management of therapeutic monoclonal antibody interference in monoclonal gammopathy monitoring","volume":"5","author":"Liu","year":"2020","journal-title":"J Appl Lab Med"},{"key":"2026100807000252400_jfag135-B2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/jalm\/jfz008","article-title":"Expression of daratumumab and elotuzumab migration by capillary electrophoresis relative to transferrin improves precision of their identification","volume":"5","author":"Huls","year":"2020","journal-title":"J Appl Lab Med"},{"key":"2026100807000252400_jfag135-B3","doi-asserted-by":"crossref","first-page":"hvae106-699","DOI":"10.1093\/clinchem\/hvae106.699","article-title":"B-342 Teclistamab interference in serum protein electrophoresis and serum immunofixation electrophoresis in patients with recurrent or relapsed multiple myeloma [Abstract]","volume":"70","author":"Whitt","year":"2024","journal-title":"Clin 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interference due to belantamab mafodotin and denosumab","volume":"127-128","author":"Jimenez","year":"2024","journal-title":"Clin Biochem"},{"key":"2026100807000252400_jfag135-B10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/jalm\/jfae142","article-title":"Distinguishing daratumumab from endogenous monoclonal proteins in serum from multiple myeloma patients using an automated mass spectrometry system","volume":"10","author":"Barnidge","year":"2025","journal-title":"J Appl Lab Med"},{"key":"2026100807000252400_jfag135-B11","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines13122933","article-title":"Mass spectrometry profiling of therapeutic antibodies in multiple myeloma: m\/z features and concordance with immunofixation electrophoresis","volume":"13","author":"Pello","year":"2025","journal-title":"Biomedicines"},{"key":"2026100807000252400_jfag135-B12","doi-asserted-by":"crossref","DOI":"10.1016\/j.cca.2026.120930","article-title":"Performance evaluation of an automated mass spectrometry system for the measurement and isotyping of monoclonal immunoglobulins","volume":"586","author":"Ashby","year":"2026","journal-title":"Clin Chem Acta"},{"key":"2026100807000252400_jfag135-B13","doi-asserted-by":"crossref","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"Drugbank 6.0: the drugbank knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2026100807000252400_jfag135-B14","author":"Expasy, Swiss Institute of Bioinformatics (SIB)"},{"key":"2026100807000252400_jfag135-B15","author":"U.S. Food and Drug Administration"},{"key":"2026100807000252400_jfag135-B16","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/jalm\/jfac064","article-title":"Characterization of casirivimab plus imdevimab, sotrovimab, and bamlanivimab plus etesevimab-derived interference in serum protein electrophoresis and immunofixation 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