{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:42:24Z","timestamp":1792233744137,"version":"4.4.0"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The polymorphic nature of the RH blood group system frequently causes serologic discrepancies relevant to transfusion practice. We describe a novel RHCE variant associated with weak, clone\u2010dependent E\u2010like reactivity and explore its molecular and structural correlates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serologic investigation was performed by standard tube testing using multiple commercial monoclonal anti\u2010E reagents. Molecular characterization utilized Illumina next\u2010generation sequencing (NGS). Computational analyses included I\u2010TASSER\u2010based model generation, integration into the 7UZQ cryogenic electron microscopy (cryo\u2010EM) erythrocyte membrane scaffold, FoldX energy calculations, three\u2010dimensional (3D)\u2010Surfer surface comparison, CASTp cavity analysis, and membrane\u2010orientation simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Donor red blood cells showed discrepant reactivity with anti\u2010E reagents, demonstrating weak positive reactions (1+) with clones GAMA402, MS\u2010260, and DEM1, but no reactivity with clone 906 or single\u2010source anti\u2010E plasma. NGS identified a novel c.680T&gt;C variant in one of two\n                      <jats:italic>RHCE*01<\/jats:italic>\n                      alleles on a c.676G homozygous background, predicting a p.Leu227Pro substitution. The allele was provisionally designated\n                      <jats:italic>RHCE*01.48<\/jats:italic>\n                      by the International Society of Blood Transfusion (ISBT) (GenBank: PZ350914). The amino acid change p.Leu227Pro is immediately adjacent to the canonical residue 226 E\/e determinant and modeling identified localized differences in surface topology, cavity architecture, and solvent exposure relative to the reference ce model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RHCE*01.48<\/jats:italic>\n                      is a novel\n                      <jats:italic>RHCE<\/jats:italic>\n                      allele associated with weak, clone\u2010dependent E\u2010like reactivity. Structural modeling generated a plausible hypothesis that localized conformational differences near the canonical E\/e determinant may contribute to the observed serologic phenotype. Recognition of such variants may help resolve genotype\u2013phenotype discrepancies and support accurate Rh typing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.70424","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:52:48Z","timestamp":1792230768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel\n                    <i>RHCE*01.48<\/i>\n                    allele associated with weak clone\u2010dependent E\u2010like reactivity: Serologic, molecular, and computational analysis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-8777","authenticated-orcid":false,"given":"Higinio","family":"Estrada\u2010Ju\u00e1rez","sequence":"first","affiliation":[{"name":"Department of Perinatal Hematology National Institute of Perinatology  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-8870","authenticated-orcid":false,"given":"Rocio","family":"Trueba\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Perinatal Hematology National Institute of Perinatology  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Mackey","sequence":"additional","affiliation":[{"name":"Reference Laboratory Miller\u2010Keystone Blood Center  Bethlehem Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Miller","sequence":"additional","affiliation":[{"name":"Reference Laboratory Miller\u2010Keystone Blood Center  Bethlehem Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8727-1679","authenticated-orcid":false,"given":"Gregory A.","family":"Denomme","sequence":"additional","affiliation":[{"name":"Medical Affairs Grifols Diagnostic Solutions  Emeryville California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Lanford","sequence":"additional","affiliation":[{"name":"Grifols Laboratory Solutions, Inc.  San Marcos Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Stef","sequence":"additional","affiliation":[{"name":"Grifols Laboratory Solutions, Inc.  San Marcos Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.16.6243"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.2.375"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2009.02221.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13357"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13061058"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.16247"},{"issue":"1","key":"e_1_2_9_8_1","first-page":"E1","article-title":"The c.845 G>A change (p.Gly282Asp) in RHCE*ce causing an E\u2010like antigen","volume":"64","author":"Rodrigues de Araujo C","year":"2024","journal-title":"Transfusion"},{"issue":"2","key":"e_1_2_9_9_1","first-page":"151","article-title":"Comprehensive phenotypic and molecular investigation of RhD and RhCE variants in Moroccan blood donors","volume":"17","author":"El Housse H","year":"2019","journal-title":"Blood Transfus"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.16034"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00792-w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(71)90324-X"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky473"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0RA03456H"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.13509"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2010.12.013"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.70424","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/trf.70424","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.70424","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:52:49Z","timestamp":1792230769000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.70424"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,17]]},"references-count":15,"alternative-id":["10.1111\/trf.70424"],"URL":"https:\/\/doi.org\/10.1111\/trf.70424","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,17]]},"assertion":[{"value":"2026-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"trf.70424"}}