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 - Lopez, Maribel Merino
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
N1 - Publisher Copyright:
Copyright © 2015 by the American Society of Nephrology.
PY - 2015/7/1
Y1 - 2015/7/1
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 usedmicroarrays and conventionalmethods 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). Usingmicroarrays, 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 themain 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.
AB - 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 usedmicroarrays and conventionalmethods 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). Usingmicroarrays, 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 themain 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.
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U2 - 10.1681/ASN.2014060588
DO - 10.1681/ASN.2014060588
M3 - Article
C2 - 25377077
AN - SCOPUS:84934753499
SN - 1046-6673
VL - 26
SP - 1711
EP - 1720
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 7
ER -