Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants

被引:55
作者
Halloran, P. F. [1 ,2 ]
Lopez, M. Merino [1 ]
Barreto Pereira, A. [1 ,3 ]
机构
[1] Alberta Transplant Appl Genom Ctr, Edmonton, AB, Canada
[2] Univ Alberta, Dept Med, Div Nephrol & Transplant Immunol, Edmonton, AB, Canada
[3] Hosp Santa Julia, Manaus, Amazonas, Brazil
基金
加拿大创新基金会;
关键词
basic (laboratory) research; science; kidney transplantation; nephrology; rejection; antibody-mediated (ABMR); microarray; gene array; CHRONIC HUMORAL REJECTION; DONOR-SPECIFIC ANTIBODIES; HUMAN-LEUKOCYTE ANTIGEN; CAPILLARY DEPOSITION; MICROARRAY DIAGNOSIS; MOLECULAR DIAGNOSIS; ALLOGRAFT SURVIVAL; RENAL-TRANSPLANTS; C4D; GLOMERULOPATHY;
D O I
10.1111/ajt.13551
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
引用
收藏
页码:908 / 920
页数:13
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