{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:45:31Z","timestamp":1783043131786,"version":"3.54.6"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,18]],"date-time":"2022-12-18T00:00:00Z","timestamp":1671321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Transplantation"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Operational tolerance after retransplantation of the intestine has never been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To two recently described intestine transplant recipients with operational tolerance, we now add a third.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Review of case record and immunological testing to confirm donor\u2010specific hyporesponsiveness in multiple immune cell compartments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Re\u2010transplanted with a multivisceral liver\u2010 and kidney\u2010inclusive intestine allograft at age 12\u2009years, this recipient self\u2010discontinued immunosuppression 14\u2009years after the retransplant and has been rejection free for 2\u2009years thereafter. As in the two previous reports, immunological testing demonstrated decreased donor\u2010specific inflammatory response of T\u2010cytotoxic memory cells and B\u2010cells, decreased presentation of donor antigen by B\u2010cells and monocytes, absence of donor\u2010specific anti\u2010HLA antibodies, circulating FOXP3\u2009+\u2009T\u2010helper cells, and intact cellular and humoral immunity to cytomegalovirus and Epstein\u2013Barr virus. Additionally, our recipient demonstrated enhanced donor\u2010activation\u2010induced apoptosis of alloreactive T\u2010cytotoxic memory cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite variable paths to tolerance which include graft versus host disease in two previous cases, and rejection\u2010related loss of the primary isolated intestinal allograft in our recipient, the three cases with operational tolerance are bound by common themes: a relatively large donor antigenic load transmitted during intestine transplantation, and donor\u2010specific hyporesponsiveness. Cell\u2010based assays suggest enhanced donor\u2010induced apoptosis of recipient T\u2010cells and circulating T\u2010regulatory cells as mechanistic links between antigenic load and donor\u2010specific hyporesponsiveness.<\/jats:p><\/jats:sec>","DOI":"10.1111\/petr.14455","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T05:49:00Z","timestamp":1671428940000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Operational tolerance after intestine re\u2010transplantation in childhood and immunological correlates. Case report and review"],"prefix":"10.1111","volume":"27","author":[{"given":"Lisa","family":"Remaley","sequence":"first","affiliation":[{"name":"Hillman Center for Pediatric Transplantation UPMC\u2010Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6508-3407","authenticated-orcid":false,"given":"Chethan","family":"Ashokkumar","sequence":"additional","affiliation":[{"name":"Hillman Center for Pediatric Transplantation UPMC\u2010Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-7234","authenticated-orcid":false,"given":"Kyle A.","family":"Soltys","sequence":"additional","affiliation":[{"name":"Hillman Center for Pediatric Transplantation UPMC\u2010Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania 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