Perforin: An intriguing protein in allograft rejection immunology (Review)

Chronic kidney disease (CKD) is a worldwide public health problem. The constantly increasing prevalence of CKD requires further research into new additional strategies in its management. The preferred treatment of end-stage renal disease (ESRD) is renal transplantation. Kidney transplant patients benefit from substantial improvement in their quality and duration of life. For these to be feasible, the long-term graft and host survival optimization of the renal transplant recipient must be ensured and chronic allograft dysfunction (CAN) must be prevented. Once an equilibrium in the allograft tolerance is established, renal transplanted patients would benefit from the withdrawal or the reduction of immunosuppression therapy. Identification of early predictive biomarkers of CAN is essential. Recent publications have revealed that in long-term immune tolerance and graft survival several populations of immune cells are involved. Starting from the identification of perforin (PRF) in pathological renal glomeruli and following with the analysis of the molecular expression of PRF in renal biopsy samples, it appears that serum PRF is one of the potential biomarkers of graft dysfunction. Over the years, this protein has captured the attention of the medical world, conducting research that could potentially lead to the discovery of an innovative biomarker. Discovering and understanding the involvement of PRF in developing CAN may open up new therapeutic pathways that would ensure the survival of the kidney transplant. In this review the authors examined the structure, the role and the present understanding of the mechanisms by which serum PRF may be involved in chronic graft dysfunction as well as its role as an immune tolerance biomarker for chronic dysfunction of the renal graft.