Introduction: Interleukin-6 is an important inflammatory cytokine which also acts as a growth factor for B-cells, plasma cells and Th17 cells. IL-6 also inhibits FoxP3+ Treg cells.  These considerations suggest blocking IL-6 may be an important method to reduce inflammation and Th17 mediated injury in kidney allografts.
Patients & Methods: Clazakizumab (Vitaeris Inc.) is a humanized monoclonal antibody aimed at the cytokine IL-6. As part of a phase I/II trial of clazakizumab for desensitization, HLA sensitized patients received anti-IL-6, 25mg SC monthly X 6 doses with monitoring of HLA antibody levels and Tregs. Patients were treated pre- and post-transplant with anti-IL-6. Transplanted patients received monthly claza 25mg SC starting 5-7 days post-transplant for 12M.  Tregs were determined by flow cytometry as CD4+,CD25+,CD127dim,FoxP3+ cell populations in CD4+ cells. Determinations were made at baseline, at transplantation and day 180 post-transplant.
Results: Nine patients were transplanted. All patients had previous transplants; 78% had cPRA 99-100%, 67% were B-cell FCMX+ and class II DSA+ @ time of transplant. Mean MFI for HLA cI & cII were: pre-desensitization vs. post claza:  cI 13062±3123 vs. 8585±4597 (p=0.05) and cII 13519±2966 vs. 8344±4836 (p =0.03). All DSA+ patients were negative by day 180 post-transplant. Mean Treg values at baseline v. at transplant did not differ (3.2+1.09% v.3.5+1.75%,p=NS). However, were significantly different at day 180 post-transplant (3.2+1.09% v.3.5+1.75% v. 12.6+9.3%, p=0.008)(Figure 1).
Conclusions: Clazakizumab desensitization reduced HLA cI/cII antibodies and allowed 9/10 highly sensitized patients to receive transplants. In addition, a dramatic increase in Treg cells at day 180 post-transplant was seen while patients were still on anti-IL-6 therapy suggesting that anti-IL-6 may induce CD4+ T-cells toward a Treg profile. This may have therapeutic implications for modifying baseline immunosuppression post-transplant.