Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside.

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disorders caused by a loss of tolerance to endogenous nuclear antigens triggering an aberrant autoimmune response targeting various tissues. Lupus nephritis (LN), a major cause of morbidity and mortality in patients with SLE, affects up to 60% of patients. The recent insights into the genetic and molecular basis of SLE and LN paved the way for newer therapies to be developed for these patients. Apart from the traditional B-cell-centered view of this disease pathogenesis, acknowledging that multiple extrarenal and intrarenal pathways contribute to kidney-specific autoimmunity and injury may help refine the individual therapeutic and prognostic characterization of such patients. Accordingly, the formerly induction-maintenance treatment strategy was recently challenged with the exciting results obtained from the trials that evaluated add-on therapy with voclosporin, belimumab, or Obinutuzumab. The scope of this review is to provide an insight into the current knowledge of LN pathogenesis and future therapeutic strategies.

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.