A comparative analysis of pig-to-rhesus corneal xenotransplantation with various immunosuppressive regimens

Introduction: Previous studies had made efforts to find the optimal regimens to reduce xenogeneic rejection in corneal xenotransplantation. However, it had not been fully determined which immunosuppressive choice would be optimal for long-term graft survival. We aimed to compare clinical results in wild type pig-to rhesus corneal xenotransplantation with various immunosuppressive regimens. Methods: Medical records of 23 Chinese rhesus macaques who had received full thickness corneal transplantation with wild-type pigs were retrospectively analyzed. They were administered various immunosuppressants including steroid, tacrolimus, anti-CD20 antibody, co-stimulation blockade (CoB) or their combinations. Graft survival, central corneal thickness, changes in plasma anti-αGal and donor-specific antibodies, aqueous complement levels, and blood effector and memory T/B cell subsets were compared between the groups with different regimens in the follow-up of 6 months. Results: Graft survival time of anti-CD20 antibody (aCD20), anti-CD40 antibody (aCD40), or anti-CD154 antibody (aCD154)-based regimen group was significantly longer than that of steroid (S) or steroid/tacrolimus (S/T) group. INF-γ T cell responses, both anti-αGal IgG and donor-specific IgG levels, along with complement responses, were effectively managed under both the aCD20 and CoB regimens. Compared with aCD154 group, aCD40 group showed higher donor specific IgG responses and aqueous C3a level. B and activated B cell concentrations were significantly lower in aCD20 group than in S, S/T, or CoB group. Conclusion: It suggests that an aCD20-based regimen produces clinical outcomes comparable to those of an aCD154-based regimen in wild-type pig-to-rhesus corneal xenotransplantation, whereas an aCD40-based regimen does not.