| CO F-014 |
| Long-term safety outcome of systemic immunosuppression in pig-to-nonhuman primate corneal xenotransplantation |
| 1Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Republic of Korea
2Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea
3Translational Xenotransplantation Research Center, Seoul National University College of Medicine and Seoul National University Hospital Biomedical Research Institute, Seoul, Republic of Korea
4Department of Experimental Animal Research, Seoul National University Hospital Biomedical Research Institute, Seoul, Republic of Korea
5Department of Ophthalmology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
6Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
7 Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea |
| Se Hyun Choi(1,2,3), Chang Ho Yoon(1,2,3), Hyun Ju Lee(1), Hong Pyo Kim(1), Jong Min Kim(3), Jeong-Hwan Che(3), Kyoung Min Roh(4), Hyuk Jin Choi(1,2,3,5), Jiyeon Kim(6,7), Eung-Soo Hwang(3,6,7), Chung-Gyu Park(3,6), Mee Kum Kim(1,2,3) |
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목적 : Safety concerns exist for corneal recipients under immunosuppression. We report long-term safety results of porcine corneal xenotransplantation under immunosuppression in nonhuman primates.
방법 : Systemic monitoring data from 49 Chinese rhesus macaques that received pig corneal transplant between 2009 and 2018 were reviewed. The recipients were divided into 4 groups depending on the systemic immunosuppressants used: (1) conventional steroid group; co-stimulation blockade groups [(2) anti-CD154 antibody, (3) anti-CD40 antibody]; and (4) commercially available immunosuppressants (anti-CD20 antibody, tacrolimus, basiliximab) group. We compared results of general condition monitoring; hematologic, biochemical and electrolyte tests; and Rhesus Cytomegalovirus (RhCMV) infection monitoring.
결과 : All recipients recovered from early weight loss. WBC counts significantly decreased at 6 months in the steroid and anti-CD154 groups. Liver and kidney dysfunction and electrolyte imbalance were not observed. The mean value of RhCMV DNA copies was consistently lower than 200 copies/ml, and antibody titers did not change over time in all groups. Tacrolimus-associated thrombotic microangiopathy was developed in one case, which resolved after tacrolimus discontinuation. In 2017, a simian varicella virus outbreak led to clinical signs in 5 that received immunosuppressive therapies, of which 3 died.
결론 : Co-stimulatory blockade-based and anti-CD20 antibody/tacrolimus-based immunosuppressive therapies seem to be comparably safe with steroid therapy in nonhuman primates receiving corneal xenotransplantation, as they did not reactivate Rhesus Cytomegalovirus and maintained manageable systemic status. Although reactivation is rare, antiviral prophylaxis for simian varicella virus should be considered in immunocompromised hosts.
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