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Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients.
J Am Soc Nephrol. 2015 Jul; 26(7):1711-20.JA

Abstract

The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline). Using microarrays, we diagnosed rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28 mixed (no borderline). Molecular assessment confirmed most conventional diagnoses (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors, particularly in mixed rejection, and improved prediction of failure. ABMR was strongly associated with increased graft loss, but TCMR was not. ABMR became common in biopsy specimens obtained >1 year post-transplant and continued to appear in all subsequent intervals. TCMR was common early but progressively disappeared over time. In 108 biopsy specimens obtained 10.2-35 years post-transplant, TCMR defined by molecular and conventional features was never observed. We conclude that the main cause of kidney transplant failure is ABMR, which can present even decades after transplantation. In contrast, TCMR disappears by 10 years post-transplant, implying that a state of partial adaptive tolerance emerges over time in the kidney transplant population.

Authors+Show Affiliations

Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada; Department of Medicine, Division of Nephrology and Transplant Immunology and phallora@ualberta.ca.Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada;Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada;Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada;Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada;Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada;Department of Surgery, University of Minnesota, Minneapolis, Minnesota;Department of Renal Medicine, Manchester Royal Infirmary, Manchester, United Kingdom;Department of Renal Medicine, Manchester Royal Infirmary, Manchester, United Kingdom; Department of Renal Medicine, Beaumont Hospital, Dublin, Ireland;Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland;Servei de Nefrologia, Hospital Vall d'Hebron, Barcelona, Spain; and.Servei de Nefrologia, Hospital Vall d'Hebron, Barcelona, Spain; and.Department of Nephrology, Medical School of Hannover, Hannover, Germany.Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada;

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25377077

Citation

Halloran, Philip F., et al. "Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients." Journal of the American Society of Nephrology : JASN, vol. 26, no. 7, 2015, pp. 1711-20.
Halloran PF, Chang J, Famulski K, et al. Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients. J Am Soc Nephrol. 2015;26(7):1711-20.
Halloran, P. F., Chang, J., Famulski, K., Hidalgo, L. G., Salazar, I. D., Merino Lopez, M., Matas, A., Picton, M., de Freitas, D., Bromberg, J., Serón, D., Sellarés, J., Einecke, G., & Reeve, J. (2015). Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients. Journal of the American Society of Nephrology : JASN, 26(7), 1711-20. https://doi.org/10.1681/ASN.2014060588
Halloran PF, et al. Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients. J Am Soc Nephrol. 2015;26(7):1711-20. PubMed PMID: 25377077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients. AU - Halloran,Philip F, AU - Chang,Jessica, AU - Famulski,Konrad, AU - Hidalgo,Luis G, AU - Salazar,Israel D R, AU - Merino Lopez,Maribel, AU - Matas,Arthur, AU - Picton,Michael, AU - de Freitas,Declan, AU - Bromberg,Jonathan, AU - Serón,Daniel, AU - Sellarés,Joana, AU - Einecke,Gunilla, AU - Reeve,Jeff, Y1 - 2014/11/06/ PY - 2014/06/19/received PY - 2014/09/07/accepted PY - 2014/11/8/entrez PY - 2014/11/8/pubmed PY - 2015/9/12/medline KW - T cells KW - antibody KW - graft rejection KW - kidney transplant KW - microarrays SP - 1711 EP - 20 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 26 IS - 7 N2 - The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline). Using microarrays, we diagnosed rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28 mixed (no borderline). Molecular assessment confirmed most conventional diagnoses (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors, particularly in mixed rejection, and improved prediction of failure. ABMR was strongly associated with increased graft loss, but TCMR was not. ABMR became common in biopsy specimens obtained >1 year post-transplant and continued to appear in all subsequent intervals. TCMR was common early but progressively disappeared over time. In 108 biopsy specimens obtained 10.2-35 years post-transplant, TCMR defined by molecular and conventional features was never observed. We conclude that the main cause of kidney transplant failure is ABMR, which can present even decades after transplantation. In contrast, TCMR disappears by 10 years post-transplant, implying that a state of partial adaptive tolerance emerges over time in the kidney transplant population. SN - 1533-3450 UR - https://www.unboundmedicine.com/medline/citation/25377077/Disappearance_of_T_Cell_Mediated_Rejection_Despite_Continued_Antibody_Mediated_Rejection_in_Late_Kidney_Transplant_Recipients_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=25377077 DB - PRIME DP - Unbound Medicine ER -