Conference Proceeding

The Myth of Sub-clinical Rejection: where we are?

Prof. Basset El Essawy,
RAKMHSU, UAE and Al-Azhar University, Egypt

Dr. Basset El Essawy M B B Ch., MSc MD PHD FASN is a Professor of Internal Medicine in AlAzhar University Egypt and Adjunct Professor of Internal Medicine Ras AlKhaimah Medical Health and Science University in UAE since 2011. He is also the President of RAK Update in Nephrology and Transplantation meeting series. He is the founder of the Nephrology unit in New Damietta faculty of Medicine in 1999. He has been working as a visiting professor and consultant in prince sultan military complex and King Fahad south military complex in KSA 2007-2011. Dr. El Essawy interest in Diabetes came during his work in pancreatic and islet transplant program in Hospital Eduard Herriot, Claude Bernard university Lyon France from 1993-1997 where he was initially in charge of islet transplant program in collaboration with the islet transplant program in San Rafael hospital in Milan. Dr. El Essawy moved to Jean Monnet university saint Etienne France 1997 where he started his work in the PhD in immunology of transplantation (health and live science) obtained in 2005. During his stay in France he has obtained 6 subspecialty diplomas in immunology and medicine. He joined the transplant center in BIDMC, Harvard Medical School in 2002 -2003 as international society of nephrology fellow. Then he continued afterword working for many years in the transplant research center in BIDMC, Harvard Medical School with special interest in proteomics and CD8 Regulatory T cells.

The presence of lymphocytic infiltration in solid organ transplantation has been defined as acute cellular rejection when it is associated with graft dysfunction and subclinical rejection (SCAR) when the graft function is quiescent. The assessment of allograft histology through prospective protocol biopsies was originally carried out for monitoring the advent of histopathologic lesions in clinically stable allografts. The presence of asymptomatic tubulointerstitial cellular infiltrates has been defined as subclinical rejection. The incidence of SCAR varies between 5% and 15% with current maintenance immunosuppressive drug regimens. The only pervious single randomized clinical trial of biopsy and corticosteroid therapy demonstrated significantly improved early structural and functional outcomes, and a (non-significant) 17% risk reduction in 4-year graft survival. Same authors, almost a decade later have reported that early protocol biopsies and corticosteroid treatment of subclinical rejection seem to have no benefit on short-term outcomes in renal transplant recipients being treated with tacrolimus, mycophenolate and prednisone. In kidney transplant situations and despite many similarities between SCAR and clinical acute rejection exist, the inflammatory activated cell infiltrates are not completely identical while graft cytokine profiles and counteractive immune responses are characterized by subtle differences that could explain why SCAR is not accompanied by immediate graft dysfunction. Evidence that SCAR contributes to chronic allograft damage (interstitial fibrosis and tubular atrophy) and negatively affects graft outcome is counterbalanced by the scarcity of controlled data proving the beneficial effect of SCAR treatment. To address this issue we used a skin transplant model in a CD4 KO mice (to study it in a single cell level) using a RPM treatment as it was reported to have a profound effect on CD8 T cells. As a surrogate model, we investigated whether CD8 T cells home to LTE DBA/2 skin allografts and if these infiltrating lymphocytes have a functional effect (i.e. rejecting or protecting) in the skin allografts. We concluded that Graft infiltrating CD8 T cells are regulatory and functionally active to protect allograft from rejection. This finding opens the field for readdressing the beneficial vs. harmful value of the presence of lymphocytic infiltration in solid organ transplantation.

Published: 28 April 2017