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Long‐term safety outcome of systemic immunosuppression in pig‐to‐nonhuman primate corneal xenotransplantation
Author(s) -
Choi Se Hyun,
Yoon Chang Ho,
Lee Hyun Ju,
Kim Hong Pyo,
Kim Jong Min,
Che JeongHwan,
Roh Kyoung Min,
Choi Hyuk Jin,
Kim Jiyeon,
Hwang Eung Soo,
Park ChungGyu,
Kim Mee Kum
Publication year - 2018
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12442
Subject(s) - immunosuppression , tacrolimus , xenotransplantation , medicine , immunology , cytomegalovirus , transplantation , virus , herpesviridae , viral disease
Background Safety concerns exist for corneal recipients under immunosuppression. We report long‐term safety results of porcine corneal xenotransplantation under immunosuppression in nonhuman primates. Methods Systemic monitoring data from 49 Chinese rhesus macaques that received pig corneal transplant between 2009 and 2018 were retrospectively reviewed. The recipients were divided into 4 groups depending on the systemic immunosuppressants used: (a) conventional steroid group; costimulation blockade groups ([b] anti‐ CD 154 antibody, [c] anti‐ CD 40 antibody); and (d) commercially available immunosuppressants (anti‐ CD 20 antibody, tacrolimus, basiliximab) group. We compared results of general condition monitoring; hematologic, biochemical, and electrolyte tests; and Rhesus Cytomegalovirus infection monitoring. Results All recipients recovered from early weight loss. White blood cell counts significantly decreased at 6 months in the steroid and anti‐ CD 154 groups. Abnormal liver and kidney function and electrolyte imbalance were not observed in all groups. The mean value of Rhesus Cytomegalovirus 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 discontinuation of tacrolimus. In 2017, a simian varicella virus outbreak led to clinical signs in 5 that received immunosuppressive therapies, of which 3 died. Conclusion Costimulatory blockade‐based and anti‐ CD 20 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.