title: Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants.
abstract: The key lesions in antibody-mediated kidney transplant rejection (ABMR) are microcirculation inflammation (peritubular capillaritis and/or glomerulitis lesions, abbreviated "pg") and glomerular double contours (cg lesions). We used these features to explore subphenotypes in 164 indication biopsies with ABMR-related diagnoses: 137 ABMR (109 pure and 28 mixed with T cell-mediated rejection [TCMR]) and 27 transplant glomerulopathy (TG), identified from prospective multicenter studies. The lesions indicated three ABMR subphenotypes: pgABMR, cgABMR, and pgcgABMR. Principal component analysis confirmed these subphenotypes and showed that TG can be reclassified as pgcgABMR (n = 17) or cgABMR (n = 10). ABMR-related biopsies included 45 pgABMR, 90 pgcgABMR, and 25 cgABMR, with four unclassifiable. Dominating all time intervals was the subphenotype pgcgABMR. The pgABMR subphenotype presented earliest (median <2 years), frequently mixed with TCMR, and was most associated with nonadherence. The cgABMR subphenotype presented late (median 9 years). Subphenotypes differed in their molecular changes, with pgABMR having the most histologic-molecular discrepancies (i.e. potential errors). Donor-specific antibody (DSA) was not identified in 29% of pgcgABMR and 46% of cgABMR, but failure rates and molecular findings were similar to cases where DSA was known to be positive. Thus, ABMR presents distinct subphenotypes, early pg-dominant, late cg-dominant, and combined pgcg phenotype, differing in time, molecular features, accompanying TCMR, HLA antibody, and probability of nonadherence.
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada.|Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: P F
authors.initials: PF
authors.lastname: Halloran
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Merino Lopez
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada.|Hospital Santa Julia, Manaus, Amazonas, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Barreto Pereira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D066027:Transplant Recipients; D023001:Transplantation Tolerance; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens
keywords: antibody-mediated (ABMR); basic (laboratory) research; gene array; kidney transplantation; microarray; nephrology; rejection; science