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signature=c4d777722a4f7e436b3fc8b1e0d0b7e0,P044 : C4d NEGATIVE ANTIBODY MEDIATED RENAL ALLOGRAFT REJ...

楚嘉纳
2023-12-01

摘要:

To describe C4d negative antibody mediated rejection (AMR) of renal allograft on Banff 2013 classification based histopathological features and circulating donor specific antibodies (DSAs). Retrospective review of more than 100 for cause renal allograft biopsies was performed. Four Cases with C4d Negative AMR were further examined for clinical and laboratory parameters associated with graft function and the DSA status at or around the time of biopsies. The HLA antibody assays were done by solid phase assays using Luminex platform. The biopsies were stained by H& E, PAS, Trichrome, and Elastic for general histological evaluations and by immunofluorescence for C4d, CD3, and CD20. Presence of capillaritis, glomerulitis, microvascular injury, and thrombotic microangiopathy with circulating HLA or non-HLA DSAs with negative staining for C4d in the peritubular capillaries (PTC) was considered as C4d negative AMR. All 4 cases had circulating DSAs at the time of biopsy. One of these cases had had three transplants, the first performed at the age of 2 lasting for 6years, second transplant at the age of 7 lasting for about 13years and the third one done at the age of 20years with C4d negative AMR noted three years post transplant. In all these cases, capillaritis and/or glomerulitis/thrombotic microangiopathy were present with negative C4d stain in the PTC. All 4 cases now show evidence of interstitial fibrosis with tubular atrophy of varying degrees. Renal allograft AMR in the absence of C4 deposition in the PTC has been recognized by the 2013 Banff. Non-complement dependent tissue injuries can result in AMR, and repeated AMR could lead to chronic antibody mediated rejection. Banff 2013 also considers evaluating molecular markers in the biopsy. So it is time to evaluate gene expression or protein array in renal biopsies to develop a molecular signature to define episodes of allograft rejection along with DSA assessment and histopathological examination. The delineation of the molecular changes induced by circulating DSAs, or alloreactive T cells may lead to novel and more effective diagnostic and therapeutical targets to assess immune mediated graft injuries and development of new therapeutic agents to treat chronic rejection.

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