TY - JOUR
T1 - Histopathology of chronic rejection in a nonhuman primate model of vascularized composite allotransplantation
AU - Mundinger, Gerhard S.
AU - Munivenkatappa, Raghava
AU - Drachenberg, Cinthia B.
AU - Ha, Jinny S.
AU - Vaca, Elbert E.
AU - Shipley, Steven T.
AU - Papadimitriou, John C.
AU - Bartlett, Stephen T.
AU - Rodriguez, Eduardo D.
AU - Barth, Rolf N.
PY - 2013/5/27
Y1 - 2013/5/27
N2 - BACKGROUND: Chronic rejection of vascularized composite allografts (VCA) is an emerging phenomenon that may decrease long-term allograft survival and impair allograft function. Although intimal hyperplasia has been reported in human hand transplants, chronic changes in VCAs remain poorly described. METHODS: We developed a nonhuman primate model of face transplantation to evaluate the effect of various immunosuppressive regimens on allograft survival that we have previously reported. Nineteen grafts were successfully transplanted and serially biopsied to assess for rejection. Five VCA grafts with long-term survival (>200 days) were weaned off immunosuppression. We performed additional histologic and immunohistochemical studies on previously collected samples. RESULTS: All five grafts developed features consistent with chronic rejection, including neointimal proliferation, transplant vasculopathy, vessel wall fibrosis, progressive luminal occlusion, and tertiary lymphoid follicles. Review of 186 serial allograft skin and subcutaneous tissue biopsies revealed that tertiary follicles and vascular changes developed in the absence of acute skin rejection. No relationship was found between alloantibody production and these changes. CONCLUSIONS: Recognition of these characteristics of VCA chronic rejection is important for diagnosis in clinical hand and face transplantation. Studies directed towards minimizing VCA chronic rejection responses may be required to improve long-term outcomes.
AB - BACKGROUND: Chronic rejection of vascularized composite allografts (VCA) is an emerging phenomenon that may decrease long-term allograft survival and impair allograft function. Although intimal hyperplasia has been reported in human hand transplants, chronic changes in VCAs remain poorly described. METHODS: We developed a nonhuman primate model of face transplantation to evaluate the effect of various immunosuppressive regimens on allograft survival that we have previously reported. Nineteen grafts were successfully transplanted and serially biopsied to assess for rejection. Five VCA grafts with long-term survival (>200 days) were weaned off immunosuppression. We performed additional histologic and immunohistochemical studies on previously collected samples. RESULTS: All five grafts developed features consistent with chronic rejection, including neointimal proliferation, transplant vasculopathy, vessel wall fibrosis, progressive luminal occlusion, and tertiary lymphoid follicles. Review of 186 serial allograft skin and subcutaneous tissue biopsies revealed that tertiary follicles and vascular changes developed in the absence of acute skin rejection. No relationship was found between alloantibody production and these changes. CONCLUSIONS: Recognition of these characteristics of VCA chronic rejection is important for diagnosis in clinical hand and face transplantation. Studies directed towards minimizing VCA chronic rejection responses may be required to improve long-term outcomes.
KW - Chronic rejection
KW - Face transplantation
KW - Immunohistochemistry
KW - Nonhuman primate
KW - Pathology
KW - Vascularized composite tissue allotransplantation
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U2 - 10.1097/TP.0b013e31828d1528
DO - 10.1097/TP.0b013e31828d1528
M3 - Article
C2 - 23694932
AN - SCOPUS:84878547820
SN - 0041-1337
VL - 95
SP - 1204
EP - 1210
JO - Transplantation
JF - Transplantation
IS - 10
ER -