Abstract
Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest.
Highlights
Short-term allograft survival has significantly increased over past decades in kidney transplantation thanks to improvements in immunosuppressive strategies
As we carefully focused our analysis on the glomeruli, all selected biopsies had histological glomerulitis (Banff g score greater than or equal to 1, g ≥ 1)
The Antibody-mediated rejection (ABMR) groups mainly consisted of male patients, 8/11 and
Summary
Short-term allograft survival has significantly increased over past decades in kidney transplantation thanks to improvements in immunosuppressive strategies. Bound DSA to endothelial cells lead to recruitment of inflammatory cells and injuries (from activation to cell lysis), which can be detected in an allograft biopsy by lesions of microvascular inflammation: glomerulitis and peritubular capillaritis. These mechanisms are thought to be complementmediated or not, the latter in up to 50% of cases [3]. The identification of complement mediation is based on the histological deposition of the complement fragment C4d on the peritubular capillaries, that can be detected by immunohistochemistry or immunofluorescence [4] These histological lesions (microvascular inflammation and C4d), as well as the detection of DSA in the serum of patients, are currently the hallmark criteria of active
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
