Circulating CD40 autoantibody and suPAR synergy drives glomerular injury

Changli Wei, Tara K. Sigdel, Minnie M. Sarwal, Jochen Reiser


Focal segmental glomerulosclerosis (FSGS) remains among the leading causes of end-stage kidney disease in children and adults, and has the highest rate of recurrence of all glomerular diseases after kidney transplantation, with florid proteinuria and accelerated renal allograft loss (1). FSGS is a heterogeneous disease with a spectrum of phenotypes based on the existence of recurrent (rFSGS) and non-recurrent (nrFSGS) disease after transplantation, which cannot be easily predicted on disease histopathology (2), and differential disease responses to treatment i.e., immunosuppression (3), plasmapheresis (4), anti-CD20 antibody, and intravenous immunoglobulin (5) in the native and post-transplant states. In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS. Various gene mutations (6) and circulating factors such as suPAR (7) and autoantibodies to CD40 and other glomerular antigens (8) have been associated with FSGS pathogenesis.