Kamal V Kanodia
Dr HL Trivedi Institute of Transplantation Sciences, India
Title: Antibody-mediated rejection in kidney transplantation
Biography
Biography: Kamal V Kanodia
Abstract
Antibody-mediated rejection (ABMR) is the most common cause of allograft failure. Acute ABMR occurs in ~ 30% of renal allograft biopsies; ~60% of late allograft dysfunctions are due to chronic ABMR. In renal transplants, acute ABMR is characterized by graft dysfunction manifesting over days and results from pre-formed/de novo donor-specific antibodies (DSA). According to revised Banff ’15 classification all three features must be present for diagnosis of acute/active AMR; (1) histologic evidence of acute tissue injury which includes microvascular inflammation (g>0 and/or peritubular capillaritis ([PTC]>0), fibrinoid necrosis/transmural arteritis (v>0), acute thrombotic microangiopathy, or acute tubular injury; (2) linear C4d staining in PTCs (C4d2/C4d3 by immunofluorescence), or C4d>0 by immunohistochemistry [IHC]. For C4d negative lesions, at least moderate microvascular inflammation (g+PTC ≥ 2)/increased expression of endothelial-associated gene transcripts (ENDATs) (3) serologic evidence of DSAs (HLA/non-HLA). For chronic ABMR, the morphologic evidence is transplanted glomerulopathy (TG) (cg>0), PTC basement membrane multilayering (on electron microscopy) and arterial intimal fibrosis of new onset. The cellular and molecular pathways regulating ABMR are still under study. However, evidence suggests B-cell and plasma cell activation results in the generation of DSAs, which bind to human leukocyte antigen (HLA) or non-HLA molecules expressed on endothelial cells within the renal allograft. In our experience of 2316 allograft biopsies from 2008 to 2016, ABMR was seen in 23.6% of patients. Mean HLA was 2.11±1.44 and mean S.Cr. was 2.7±1.45mg/dL.