Comparative effect of various immunosuppressive regimens on clinical and immunological outcome in wild-type pig-to-rhesus corneal xenotransplantation

초록

Purpose : To compare clinical and immunological outcome depending on various immunosuppressant agents in wild type pig-to rhesus corneal xenotransplantation. Methods : Medical records of 23 Chinese rhesus macaques who had conducted full thickness corneal transplantation with genetically unmodified SNU miniature pigs were retrospectively analyzed. They were injected various immunosuppressants including steroid, steroid/tacrolimus combination, anti-CD20 antibody/tacrolimus combination or co-stimulation blockade (anti-CD40 or anti-CD154 antibody) as programmed schedules. Graft survival, intraocular pressure (IOP), central corneal thickness (CCT), plasma anti-αGal and donor-specific antibodies, changes of aqueous complement levels, and changes in blood T and B cell subsets, were compared among the groups with different immunosuppressants. Results : Graft survival time of steroid (S) or steroid/tacrolimus (S/T) group was significantly shorter than that of anti-CD20 antibody/tacrolimus (aCD20/T) or co-stimulation blockade (CoB) group. IOP and CCT in surviving grafts did not show significant differences among groups. Plasma anti-αGal IgG and donor-specific IgG showed tendency to increase until 1 month in S group while they were well controlled in aCD20/T and CoB groups until 6 months. Aqueous C3a level increased in S and S/T groups. Activated B and B cell concentration were lower in aCD20/T group than in S, S/T, or CoB group. When comparing proportional changes in biological profiles among sub-groups, the suppressive effect on donor specific IgG and aqueous C3a were greater in aCD154 and aCD20/T groups compared to aCD40 group within 1month, and this suppressive effect was comparable between aCD154 and aCD20 groups. The suppressive effect was comparable in both CoB and aCD20 Ab groups at 6 months. Conclusions : It suggests that the aCD154 or anti-CD20 antibody/tacrolimus based immunosuppressive regimens superior effects on both clinical and immunological outcome in wild type pig-to-rhesus corneal xenotransplantation than steroid, steroid/tacrolimus combination or aCD40 antibody regimens.