{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T06:14:30Z","timestamp":1771740870120,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>IgG against alloantigens on transfused RBC can lead to antibody\u2010mediated immune enhancement (AMIE). AMIE has properties not found in other forms of alloimmunization, including rapid clearance of RBCs, a requirement for Fc\u2010gamma receptors on dendritic cells, and no dependence on IFNAR. A spleen is required for alloimmunization to transfused RBCs under normal conditions but its role in AMIE has not been assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>Mice with surgical splenectomy or sham surgery were infused with monoclonal IgG against model antigens (HOD or KEL) followed by a transfusion of respective transgenic RBCs. Antibody binding to transfused RBCs, antigen\u2010modulation, and RBC clearance were assessed by flow cytometry. IgM and IgG to the HOD and KEL alloantigens were quantified by flow cytometry\u2010based crossmatch.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IgG to either HOD or KEL caused brisk clearance of RBCs with almost complete antigen modulation at 24\u2009h and a strong enhancement of both IgM and IgG in sham\u2010operated animals. In splenectomized animals, AMIE was eliminated; antigen\u2010modulation occurred but with decreased kinetics and magnitude; and RBC clearance was the same as in sham animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current study extends the role of spleen as a general requirement for all known pathways of RBC alloimmunization studied thus far. However, the dissociation of clearance and antigen\u2010modulation from AMIE shown in the current study raises the possibility that antigen\u2010modulation and AMIE are correlated due to a confounding common cause (i.e., IgG binding RBCs).<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.18148","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T03:52:57Z","timestamp":1738295577000},"page":"453-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A spleen is required for antibody mediated immune enhancement but not for <scp>RBC<\/scp> clearance or antigen\u2010modulation in mice"],"prefix":"10.1111","volume":"65","author":[{"given":"Ariel M.","family":"Hay","sequence":"first","affiliation":[{"name":"Beirne Carter Immunology Center University of Virginia  Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-4932","authenticated-orcid":false,"given":"Arijita","family":"Jash","sequence":"additional","affiliation":[{"name":"Beirne Carter Immunology Center University of Virginia  Charlottesville Virginia USA"},{"name":"Department of Pathology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22898-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2005.11.005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-3274(02)00066-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2007.00945.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01516"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018591"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2006.00946.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14307"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15482"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2009.02200.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.162685"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI167665"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-214387"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.17197"},{"key":"e_1_2_7_16_1","first-page":"51","article-title":"Hypoxic storage of murine red blood cells improves energy metabolism and post\u2010transfusion recoveries","volume":"21","author":"Hay A","year":"2022","journal-title":"Blood Transfus"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2022.12.009"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1040"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.629608"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151720"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1992.tb06869.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-724732"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14939"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018018408"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2009.03.002"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-749432"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.18148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:24:49Z","timestamp":1754915089000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.18148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/trf.18148"],"URL":"https:\/\/doi.org\/10.1111\/trf.18148","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}