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We present the case of a man in his mid-30s, transplanted 5 years prior, who developed new heart failure 4 weeks after PCR-confirmed influenza A infection. Endomyocardial biopsy revealed concomitant high-grade acute cellular rejection and antibody-mediated rejection. Despite a pretransplant panel reactive antibody of 0%, a negative virtual crossmatch and consistently therapeutic tacrolimus levels, de novo donor-specific antibodies developed. Even with aggressive therapy, he died as a result of graft failure. Transplant recipients must be regularly vaccinated, and clinicians should maintain a high degree of suspicion of graft failure in the immediate aftermath of influenza infection.<\/jats:p>","DOI":"10.1136\/bcr-2025-265384","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T21:30:16Z","timestamp":1751405416000},"page":"e265384","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Combined cellular and antibody-mediated rejection of orthotopic heart transplant following influenza A infection"],"prefix":"10.1136","volume":"18","author":[{"given":"Joseph","family":"Crowder","sequence":"first","affiliation":[{"name":"Internal Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5143-1431","authenticated-orcid":false,"given":"Jeffrey F","family":"Spindel","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Shelman","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasilios","family":"Katsadouros","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Kolodziej","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"2025082708530575000_18.7.e265384.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2018.07.022"},{"key":"2025082708530575000_18.7.e265384.2","first-page":"583","article-title":"Influence of HLA Mismatch on Rejection after Heart Transplantation: A Multiinstitutional Study. 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