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7 záznamů v Medvik Filtry

Článek

Relating Molecular T Cell-mediated Rejection Activity in Kidney Transplant Biopsies to Time and to Histologic Tubulitis and Atrophy-fibrosis

Madill-Thomsen, Katelynn S
Autor Madill-Thomsen, Katelynn S Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada
Böhmig, Georg A
Autor Böhmig, Georg A Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Bromberg, Jonathan
Autor Bromberg, Jonathan Department of Surgery, University of Maryland, Baltimore, MD
Einecke, Gunilla
Autor Einecke, Gunilla Department of Nephrology, Hannover Medical School, Hannover, Germany
Eskandary, Farsad
Autor Eskandary, Farsad Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Gupta, Gaurav
Autor Gupta, Gaurav Division of Nephrology, Virginia Commonwealth University, Richmond, VA
Myslak, Marek
Autor Myslak, Marek Department of Clinical Interventions, Department of Nephrology and Kidney Transplantation SPWSZ Hospital, Pomeranian Medical University, Szczecin, Poland
Viklicky, Ondrej
Autor Viklicky, Ondrej Department of Nephrology and Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Perkowska-Ptasinska, Agnieszka
Autor Perkowska-Ptasinska, Agnieszka Department of Pathology, Medical University of Warsaw, Warsaw, Poland
Solez, Kim
Autor Solez, Kim Department of Laboratory Medicine and Pathology, Division of Anatomical Pathology, University of Alberta, Edmonton, Canada

Transplantation. 2023 ; 107 (5) : 1102-1114. [pub] 20230422

ISSN 1534-6080
Medvik
Zdroj

BACKGROUND: We studied the variation in molecular T cell-mediated rejection (TCMR) activity in kidney transplant indication biopsies and its relationship with histologic lesions (particularly tubulitis and atrophy-fibrosis) and time posttransplant. METHODS: We examined 175 kidney transplant biopsies with molecular TCMR as defined by archetypal analysis in the INTERCOMEX study ( ClinicalTrials.gov #NCT01299168). TCMR activity was defined by a molecular classifier. RESULTS: Archetypal analysis identified 2 TCMR classes, TCMR1 and TCMR2: TCMR1 had higher TCMR activity and more antibody-mediated rejection ("mixed") activity and arteritis but little hyalinosis, whereas TCMR2 had less TCMR activity but more atrophy-fibrosis. TCMR1 and TCMR2 had similar levels of molecular injury and tubulitis. Both TCMR1 and TCMR2 biopsies were uncommon after 2 y posttransplant and were rare after 10 y, particularly TCMR1. Within late TCMR biopsies, TCMR classifier activity and activity molecules such as IFNG fell progressively with time, but tubulitis and molecular injury were sustained. Atrophy-fibrosis was increased in TCMR biopsies, even in the first year posttransplant, and rose with time posttransplant. TCMR1 and TCMR2 both reduced graft survival, but in random forests, the strongest determinant of survival after biopsies with TCMR was molecular injury, not TCMR activity. CONCLUSIONS: TCMR varies in intensity but is always strongly related to molecular injury and atrophy-fibrosis, which ultimately explains its effect on survival. We hypothesize, based on the reciprocal relationship with hyalinosis, that the TCMR1-TCMR2 gradient reflects calcineurin inhibitor drug underexposure, whereas the time-dependent decline in TCMR activity and frequency after the first year reflects T-cell exhaustion.