{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:29:18Z","timestamp":1753878558719,"version":"3.41.2"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1U01AI079223","2U19AI051731-11","U01AI084150"],"award-info":[{"award-number":["1U01AI079223","2U19AI051731-11","U01AI084150"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010915","name":"American Society of Transplant Surgeons","doi-asserted-by":"publisher","award":["ASTS\u2010Genentech Scientist Scholarship"],"award-info":[{"award-number":["ASTS\u2010Genentech Scientist Scholarship"]}],"id":[{"id":"10.13039\/100010915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["P51RR165"],"award-info":[{"award-number":["P51RR165"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Transplantation"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Belatacept, the CD28\u2010B7 costimulation pathway inhibitor, has been approved as a calcineurin inhibitor (CNI) alternative in kidney transplantation. Although costimulation blockade (CoB) allows for CNI avoidance, it is associated with increased rates of early rejection, prompting a search for agents to pair with belatacept. Methotrexate (MTX) is an antimetabolite that has been found to be complimentary with abatacept, a lower affinity CD28\u2010B7\u2010specific analogue of belatacept, in the treatment of rheumatoid arthritis (RA). We examined whether this synergy would extend to prevention of kidney allograft rejection. Rhesus macaques underwent kidney transplantation treated with abatacept maintenance therapy with either a steroid taper, MTX, or both. The combination of abatacept maintenance with steroids prolonged graft survival compared to untreated historical controls and previous reports of abatacept monotherapy. The addition of MTX did not provide additional benefit. These data demonstrate that abatacept with adjuvant therapy may delay the onset of acute rejection, but fail to show synergy between abatacept and MTX beyond that of steroids. These findings indicate that MTX is unlikely to be a suitable adjuvant to CoB in kidney transplantation, but also suggest that with further modification, a CoB regimen used for advanced RA may suffice for RA patients requiring kidney transplantation.<\/jats:p>","DOI":"10.1111\/ctr.13568","type":"journal-article","created":{"date-parts":[[2019,4,21]],"date-time":"2019-04-21T13:16:41Z","timestamp":1555852601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Corticosteroids and methotrexate as adjuvants to costimulation blockade in non\u2010human primate renal transplantation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8919-2445","authenticated-orcid":false,"given":"Douglas J.","family":"Anderson","sequence":"first","affiliation":[{"name":"Emory Transplant Center Emory University Atlanta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise J.","family":"Lo","sequence":"additional","affiliation":[{"name":"Emory Transplant Center Emory University Atlanta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Leopardi","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingqing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Strobert","sequence":"additional","affiliation":[{"name":"Yerkes National Primate Center Emory University Atlanta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe B.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Yerkes National Primate Center Emory University Atlanta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian P.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Emory Transplant Center Emory University Atlanta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan D.","family":"Kirk","sequence":"additional","affiliation":[{"name":"Emory Transplant Center Emory University Atlanta Georgia"},{"name":"Department of Surgery Duke University Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.03005.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2010.03016.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506027"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14353"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03736.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200210150-00006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/381434a0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.1.542"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000261722.02697.75"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8789"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/72162"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43895"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13628"},{"issue":"4","key":"e_1_2_8_15_1","first-page":"473","article-title":"Methotrexate in rheumatoid arthritis","volume":"58","author":"Swierkot J","year":"2006","journal-title":"Pharmacol Rep"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310203"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.60.8.729"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2005.07.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61054-9"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007611-196409000-00016"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021359"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-70-16939"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000203749"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67530-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198603203141201"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.149294"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163998"},{"issue":"5","key":"e_1_2_8_28_1","first-page":"III47","article-title":"Reversal of recalcitrant cardiac allograft rejection with methotrexate","volume":"78","author":"Costanzo\u2010Nordin MR","year":"1988","journal-title":"Circulation"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199011000-00007"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-4975(95)00414-G"},{"issue":"2","key":"e_1_2_8_31_1","first-page":"169","article-title":"Effects of methotrexate on acute rejection and cardiac allograft vasculopathy in heart transplant recipients","volume":"16","author":"Costanzo MR","year":"1997","journal-title":"J Heart Lung Transplant"},{"issue":"4","key":"e_1_2_8_32_1","first-page":"726","article-title":"Methotrexate therapy for complex graft rejection in pediatric heart transplant recipients","volume":"14","author":"Chinnock R","year":"1995","journal-title":"J Heart Lung Transplant"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(02)03665-5"},{"issue":"9","key":"e_1_2_8_34_1","first-page":"948","article-title":"Methotrexate can halt the progression of bronchiolitis obliterans syndrome in lung transplant recipients","volume":"15","author":"Dusmet M","year":"1996","journal-title":"J Heart Lung Transplant"},{"issue":"11","key":"e_1_2_8_35_1","first-page":"1130","article-title":"Methotrexate for lung transplant recipients with steroid\u2010resistant acute rejection","volume":"15","author":"Cahill BC","year":"1996","journal-title":"J Heart Lung Transplant"},{"issue":"5","key":"e_1_2_8_36_1","first-page":"3046","article-title":"Methotrexate is effective in preventing acute and potentially chronic renal allograft rejection","volume":"26","author":"Michael B","year":"1994","journal-title":"Transplant Proc"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035075"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080813"},{"key":"e_1_2_8_39_1","unstructured":"Orencia package inserthttps:\/\/packageinserts.bms.com\/pi\/pi_orencia.pdf. Accessed April 29 2019"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2676"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.09.001"},{"key":"e_1_2_8_42_1","unstructured":"National Research Council.Guide for the Care and Use of Laboratory Animals 8th Edition.Washington DC:The National Academies Press.2011."},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1976.40.1.101"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04342.x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.00749.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008933"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13486"},{"issue":"10","key":"e_1_2_8_48_1","first-page":"1","article-title":"Antigen\u2010specificity of T\u2010cell infiltrates in biopsies with T\u2010cell mediated rejection and BK polyomavirus viremia: analysis by next generation sequencing","volume":"16","author":"Zeng G","year":"2016","journal-title":"Am J Transplant"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03929.x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04184.x"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04180.x"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.7.3348"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063842"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000116"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300470"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601538"}],"container-title":["Clinical Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ctr.13568","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ctr.13568","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ctr.13568","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T20:22:42Z","timestamp":1694377362000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ctr.13568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,7]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1111\/ctr.13568"],"URL":"https:\/\/doi.org\/10.1111\/ctr.13568","archive":["Portico"],"relation":{},"ISSN":["0902-0063","1399-0012"],"issn-type":[{"type":"print","value":"0902-0063"},{"type":"electronic","value":"1399-0012"}],"subject":[],"published":{"date-parts":[[2019,5,7]]},"assertion":[{"value":"2018-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13568"}}