{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:50:54Z","timestamp":1784119854573,"version":"3.55.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014764","name":"China International Medical Foundation","doi-asserted-by":"publisher","award":["Z-2017-24-2037"],"award-info":[{"award-number":["Z-2017-24-2037"]}],"id":[{"id":"10.13039\/501100014764","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020196","name":"Shandong Provincial Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["SDCX-ZG-202400070"],"award-info":[{"award-number":["SDCX-ZG-202400070"]}],"id":[{"id":"10.13039\/501100020196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Red blood cells (RBCs) have the capability to bind and transport a variety of substances. The aim of this study is to investigate the potential of circulating RBCs as carriers of monoclonal immunoglobulins (M proteins).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients who were newly diagnosed with monoclonal gammopathy in the Nephrology Department of Shandong Provincial Hospital affiliated with Shandong First Medical University from April 2023 to December 2024 were included in this study. Western blots were performed on RBC membrane proteins using primary antibodies against human IgG, IgM, IgA, kappa, and lambda.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty-nine patients with monoclonal gammopathy were enrolled in this study. Substantial increases in the amounts of erythrocyte-bound immunoglobulins, characterized by monoclonal properties, were observed. Among the 49 patients, 45 (91.8%) had M proteins detected on RBCs, 38 (77.6%) had abnormal serum capillary electrophoresis and immunosubtraction (CE\/IS) results, 36 (75.3%) had abnormal serum free light-chain (sFLC) ratios, and 32 (65.3%) had abnormal serum total light-chain (sTLC) ratios. 53.1% (26\/49) of patients with monoclonal gammopathy had concordant results between erythrocyte Western blot and CE\/IS. 22.4% (11\/49) of patients had negative serum CE\/IS results but extrinsic monoclonal immunoprotein bands on RBCs, which were consistent with the findings from sFLC, bone marrow flow cytometry, or renal histopathology. 16.3% (8\/49) of patients had abnormal but inconsistent results between serum CE\/IS and erythrocyte electrophoresis. Four (8.2%) patients had no or polyclonal immunoprotein bands on RBCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Monoclonal immunoglobulins were presented on erythrocytes, which may serve as a supplementary diagnostic indicator for the detection of M proteins.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1636162","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T05:45:43Z","timestamp":1757655943000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Monoclonal immunoglobulins on red blood cells: a potential supplementary diagnostic indicator for monoclonal gammopathies"],"prefix":"10.3389","volume":"16","author":[{"given":"Benxia","family":"Bing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjuan","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/leu.2008.291","article-title":"Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma","volume":"23","author":"Kyle","year":"2009","journal-title":"Leukemia"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/46.8.1230","article-title":"Understanding and identifying monoclonal gammopathies","volume":"46","author":"Attaelmannan","year":"2000","journal-title":"Clin Chem"},{"key":"B3","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.clinbiochem.2017.05.001","article-title":"Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma","volume":"51","author":"Willrich","year":"2018","journal-title":"Clin Biochem"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2015-0862","article-title":"Challenges of measuring monoclonal proteins in serum","volume":"54","author":"Keren","year":"2016","journal-title":"Clin Chem Lab Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2011.171314","article-title":"Long-term biological variation of serum protein electrophoresis M-spike, urine M-spike, and monoclonal serum free light chain quantification: implications for monitoring monoclonal gammopathies","volume":"57","author":"Katzmann","year":"2011","journal-title":"Clin Chem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2015.253740","article-title":"Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry","volume":"62","author":"Mills","year":"2016","journal-title":"Clin Chem"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2019-1104","article-title":"An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part I: factors impacting limit of quantitation of serum protein electrophoresis","volume":"58","author":"Turner","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4065\/81.12.1575","article-title":"Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays","volume":"81","author":"Katzmann","year":"2006","journal-title":"Mayo Clin Proc"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0794-CP","article-title":"Laboratory detection and initial diagnosis of monoclonal gammopathies","volume":"146","author":"Keren","year":"2022","journal-title":"Arch Pathol Lab Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a004075","article-title":"Natural selection on the erythrocyte surface","volume":"19","author":"Baum","year":"2002","journal-title":"Mol Biol Evol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-3992","article-title":"Red blood cells express a functional endothelial nitric oxide synthase","volume":"107","author":"Kleinbongard","year":"2006","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201706-1161OC","article-title":"Red blood cells homeostatically bind mitochondrial DNA through TLR9 to maintain quiescence and to prevent lung injury","volume":"197","author":"Hotz","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.07.028","article-title":"Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries","volume":"97","author":"Verma","year":"2020","journal-title":"Kidney Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-4989-8_19","article-title":"Considering the vascular hypothesis of Alzheimer\u2019s disease: effect of copper associated amyloid on red blood cells","volume":"765","author":"Lucas","year":"2013","journal-title":"Adv Exp Med Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afv009","article-title":"The peripheral blood of Abeta binding RBC as a biomarker for diagnosis of Alzheimer\u2019s disease","volume":"44","author":"Lan","year":"2015","journal-title":"Age Ageing"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1998.38898375519.x","article-title":"Quantitation of red cell-bound immunoprotein","volume":"38","author":"Sokol","year":"1998","journal-title":"Transfusion"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.16.6137","article-title":"Co-clustering of denatured hemoglobin with band 3: its role in binding of autoantibodies against band 3 to abnormal and aged erythrocytes","volume":"83","author":"Schluter","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1159\/000203858","article-title":"A quantitative ELISA for measuring red cell-bound immunoglobulins","volume":"95","author":"Hazlehurst","year":"1996","journal-title":"Acta Haematol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201700236","article-title":"MALDI mass spectrometry imaging: A novel tool for the identification and classification of amyloidosis","volume":"17","author":"Winter","year":"2017","journal-title":"Proteomics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"8","DOI":"10.4172\/jpb.S8-002","article-title":"Insight into the protein composition of immunoglobulin light chain deposits of eyelid, orbital and conjunctival amyloidosis","author":"Nielsen","year":"2014","journal-title":"J Proteomics Bioinform"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V55.5.817.817","article-title":"Binding of immunoglobulin classes to subpopulations of human red blood cells separated by density-gradient centrifugation","volume":"55","author":"Alderman","year":"1980","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.15.5498","article-title":"Erythrocyte homeostasis: antibody-mediated recognition of the senescent state by macrophages","volume":"83","author":"Singer","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V65.5.1127.1127","article-title":"Cell-bound autologous immunoglobulin in erythrocyte subpopulations from patients with sickle cell disease","volume":"65","author":"Green","year":"1985","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2257.1984.tb00561.x","article-title":"Red blood cell membrane-bound IgG: demonstration of antibodies in patients with autoimmune haemolytic anaemia and immune complexes in patients with rheumatic diseases","volume":"6","author":"Hansen","year":"1984","journal-title":"Clin Lab Haematol"},{"key":"B25","article-title":"A newly discovered function of the erythrocyte: transport of immune complexes to the liver","volume":"41","author":"Halma","year":"1992","journal-title":"Neth J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2016.1232647","article-title":"Capillary electrophoresis\/immunosubtraction as a better alternative to immunofixation for detecting and immunotyping serum monoclonal proteins in patients with immunoglobulin light chain (AL) amyloidosis","volume":"23","author":"Miyazaki","year":"2016","journal-title":"Amyloid"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1309\/1L3CG8GK6F8VYNYH","article-title":"Performance of the Sebia CAPILLARYS 2 for detection and immunotyping of serum monoclonal paraproteins","volume":"128","author":"Yang","year":"2007","journal-title":"Am J Clin Pathol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfab067","article-title":"Immunotyping provides equivalent results to immunofixation in a population with a high prevalence of monoclonal gammopathies","volume":"6","author":"Thoren","year":"2021","journal-title":"J Appl Lab Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1636162\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T05:45:43Z","timestamp":1757655943000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1636162\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2025.1636162"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1636162","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]},"article-number":"1636162"}}