Complement activation and Antibody mediated rejection

Recently at the ATC 2010, there was a presentation about Terminal Complement Inhibition Decreases Early Acute Humoral Rejection in Sensitized Renal Transplant Recipients.

Transplanting highly sensitized patients remains a significant problem in kidney transplantation.  Methods of decreasing alloantibody include plasma exchange, IVIG and Rituximab, however the effect on HLA-antibodies are limited.  Eculizumab inhibits the complement cascade at C5 and therefore may be able to block the effector pathway of antibody mediated rejection.  A study presented at ATC 2010 had 17 incompatible (B flow cytometry crossmatch median channel shift > 340) highly sensitized recipients of living donor allografts received eculizumab post transplant and were compared to 51 historic controls treated with plasmapheresis and IVIG.  Patients received weekly doses of Eculizumab post transplant until they had a spontaneous decrease in donor specific antibody (B flow crossmatch <200 channel shift).   1 of the 16 patients treated with Eculizumab experienced antibody mediated rejection (6.25%) compared to 40% of the historic controls.  However, in the relatively short f/u period (1-17 months) four patients developed signs of chronic injury including 2 with transplant glomerulopathy.  

Conclusions/ comments:  Terminal complement inhibition significantly reduces humoral rejection.  However, the optimum dosing is unknown and long term graft survival may be jeopardized by chronic antibody mediated damage.  Long term f/u will be needed in these patients and a trial evaluating it in sensitized waitlisted patients would also be useful.

Reported by Vinay Nair