{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:43:24Z","timestamp":1753879404255,"version":"3.41.2"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"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":["Transplant Infectious Dis"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Maintenance with \u201ceverolimus + reduced dose tacrolimus\u201d (Ev + Tac<jats:sub>low<\/jats:sub>) was reported to reduce the risk of viral infections compared to \u201ctacrolimus + mycophenolate mofetil\u201d (Tac + MMF). Here we examined viremia and viral\u2010specific T\u2010cell (viral\u2010Tc) responses in patients treated with Ev + Tac<jats:sub>low<\/jats:sub> versus Tac + MMF in highly\u2010human leukocyte antigen (HLA)\u2010sensitized patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HLA\u2010sensitized (HS) kidney transplant patients were monitored pre\u2010 and post\u2010transplant for viremia (cytomegalovirus (CMV), BK, and Epstein\u2013Barr virus (EBV)) by polymerase chain reaction (PCR) in 19 Ev + Tac<jats:sub>low<\/jats:sub> and 48 Tac + MMF patients. For CMV PCR analysis, we compared infection rates in 19 Ev + Tac<jats:sub>low<\/jats:sub> patients to 48 CMV D+\/R\u2010 (#28) or CMV D\u2010\/R\u2010 (#20) Tac + MMF patients. CMV\u2010specific cytotoxic T cell (CMV\u2010Tc) and EBV\u2010specific cytotoxic T cell (EBV\u2010Tc) were evaluated by cytokine flow cytometry, and donor\u2010specific antibody (DSA) levels by Luminex for selected patients in both groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CMV and EBV viremia rates were similar in Ev + Tac<jats:sub>low<\/jats:sub> versus Tac + MMF patients, but BK virus (BKV) rates were significantly higher in Ev + Tac<jats:sub>low<\/jats:sub> patients. No patient in either group developed BK virus\u2010associated allograft nephropathy (BKAN) or post\u2010transplant lymphoproliferative disorders (PTLD). CMV\u2010Tc and EBV\u2010Tc decreased significantly after alemtuzumab induction but returned to pre\u2010treatment levels 1\u20132 months post\u2010transplant in most patients. de novo DSA was similar in both groups as were patient and graft survival and graft rejection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CMV\u2010Tc and EBV\u2010Tc were similar in Ev + Tac<jats:sub>low<\/jats:sub> and Tac + MMF patients. EBV and CMV viremia rates were similar over 1 year. BKV rates were significantly higher in Ev + Tac<jats:sub>low<\/jats:sub> patients suggesting no benefit for Ev + Tac<jats:sub>low<\/jats:sub> in enhancing viral\u2010Tc effector functions or limiting viral infections.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tid.13805","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T20:45:13Z","timestamp":1645821913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Viral\u2010specific cytotoxic T\u2010cell responses in HLA\u2010sensitized kidney transplant patients maintained on everolimus and low\u2010dose tacrolimus"],"prefix":"10.1111","volume":"24","author":[{"given":"Shili","family":"Ge","sequence":"first","affiliation":[{"name":"Transplant Immunology Laboratory Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie","family":"Chu","sequence":"additional","affiliation":[{"name":"Transplant Immunology Laboratory Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Tang","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Kahwaji","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Artur","family":"Karasyov","sequence":"additional","affiliation":[{"name":"Transplant Immunology Laboratory Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darly","family":"Lovato","sequence":"additional","affiliation":[{"name":"Transplant Immunology Laboratory Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Vo","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jua","family":"Choi","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley C.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-6613","authenticated-orcid":false,"given":"Ruan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Transplant Immunology Laboratory Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mieko","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Transplant Immunology Laboratory Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03710411"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12465"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000437671.78716.f3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000165110.78397.93"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5672523"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2010.03400.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000080685.31697.FC"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000064"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707894"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.02017.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181d0e15e"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010018"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001447"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001432"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041540103"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3201"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00228"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2926"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370219"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182007be2"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03693.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1994.1193"},{"issue":"4","key":"e_1_2_9_24_1","first-page":"544","article-title":"Inhibition of T and B lymphocyte proliferation by rapamycin","volume":"72","author":"Kay JE","year":"1991","journal-title":"Immunology"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830201017"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/435342"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2017.02.007"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1498-3"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1086\/653737"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.5527\/wjn.v4.i3.354"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13661"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12590"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00299.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2010.11.006"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2003.00647.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000438636.52085.50"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001573"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001573"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018010009"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13649"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2015.04.017"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12848"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002626"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12151"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2017.06.030"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13679"},{"issue":"1","key":"e_1_2_9_47_1","first-page":"14","article-title":"Conversion from tacrolimus to everolimus with complete and early glucocorticoid withdrawal after kidney transplantation: a randomised trial","volume":"76","author":"Bouamar R","year":"2018","journal-title":"Neth J Med"}],"container-title":["Transplant Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tid.13805","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/tid.13805","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tid.13805","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T23:15:26Z","timestamp":1693005326000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tid.13805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,3]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/tid.13805"],"URL":"https:\/\/doi.org\/10.1111\/tid.13805","archive":["Portico"],"relation":{},"ISSN":["1398-2273","1399-3062"],"issn-type":[{"type":"print","value":"1398-2273"},{"type":"electronic","value":"1399-3062"}],"subject":[],"published":{"date-parts":[[2022,3,3]]},"assertion":[{"value":"2021-10-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13805"}}