{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T08:37:39Z","timestamp":1773218259046,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T00:00:00Z","timestamp":1439164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["N. 141\/RF-2010-2303934."],"award-info":[{"award-number":["N. 141\/RF-2010-2303934."]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Hereditary spherocytosis (HS) is a congenital hemolytic anemia caused by defects in red blood cell (RBC) membrane proteins leading to premature RBC clearance in the spleen. The presence of RBC autoantibodies has never been extensively investigated in HS.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>RBC antibody\u2013bound immunoglobulin (Ig)G was investigated in 91 consecutive HS patients by mitogen\u2010stimulated direct antiglobulin test (MS\u2010DAT), a sensitive method able to magnify latent RBC antibody autoimmunity and related with hemolytic variables, previous splenectomy, and type of membrane defect.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A total of 61% of HS cases had RBC antibodies by MS\u2010DAT (29 Band 3, 17 spectrin deficiency, and nine no defined defect). The amount of RBC\u2010bound IgG was greater in HS compared with controls (236\u2009\u00b1\u2009192 ng\/mL vs. 52\u2009\u00b1\u200929 ng\/mL, p\u2009&lt;\u20090.0001), although lower than that observed in autoimmune hemolytic anemia (AIHA; 634\u2009\u00b1\u2009371 ng\/mL vs. 236\u2009\u00b1\u2009192 ng\/mL, p\u2009&lt;\u20090.0001). Western blot experiments showed that purified IgG fraction from MS\u2010DAT\u2013positive patients bind to \u03b1\u2010 and \u03b2\u2010spectrin, Band 3, and Band 4.9. Positive cases displayed increased reticulocytosis and slightly reduced hemoglobin (Hb) values compared to negative ones. Patients displaying RBC\u2010bound IgG of more than 250 ng\/mL (the positive threshold of AIHA) showed increased number of spherocytes and mainly had spectrin deficiency. RBC\u2010bound IgG and free Hb increased over time after storage at 4\u00b0C, a surrogate of ex vivo aging, more evidently in HS than controls, and particularly in Band 3 deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>RBC autoantibodies were detected by MS\u2010DAT in more than a half of HS patients. Positive cases showed a more evident hemolytic pattern suggesting a pathogenic role of these autoantibodies in RBC opsonization and splenic removal.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.13257","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T04:37:32Z","timestamp":1439267852000},"page":"2930-2938","source":"Crossref","is-referenced-by-count":14,"title":["Detection of red blood cell antibodies in mitogen\u2010stimulated cultures from patients with hereditary spherocytosis"],"prefix":"10.1111","volume":"55","author":[{"given":"Anna","family":"Zaninoni","sequence":"first","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Vercellati","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca G.","family":"Imperiali","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna P.","family":"Marcello","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Fattizzo","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Fermo","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Bianchi","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Grossi","sequence":"additional","affiliation":[{"name":"Experimental Laboratory of Immunological and Rheumatologic Researches IRCCS Istituto Auxologico Italiano"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"UO Laboratorio Centrale di Analisi Chimico Cliniche e Microbiologiche Dipartimento Dei Servizi Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostino","family":"Cortelezzi","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"},{"name":"Universit\u00e0 Degli Studi di Milano Milan Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Zanella","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilma","family":"Barcellini","sequence":"additional","affiliation":[{"name":"UO Oncoematologia UOS Fisiopatologia delle Anemie"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,10]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"170","article-title":"Genetics of spherocytosis","volume":"14","author":"Morton NE","year":"1962","journal-title":"Am J Hum Gen"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1981.tb00448.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1999.01130.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01715351"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2006.03.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(96)90021-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2005.1.13"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)8:2<97::AID-HUMU1>3.0.CO;2-M"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.1997.0160"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105844200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106031"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.10.2894"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(96)90027-X"},{"key":"e_1_2_7_15_1","first-page":"994","article-title":"Erythroid membrane protein defects in hereditary spherocytosis. 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