title: Histopathology of chronic rejection in a nonhuman primate model of vascularized composite allotransplantation.
abstract: 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.
authors.affiliation: Division of Plastic and Reconstructive Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Gerhard S
authors.initials: GS
authors.lastname: Mundinger
authors.forename: Raghava
authors.initials: R
authors.lastname: Munivenkatappa
authors.forename: Cinthia B
authors.initials: CB
authors.lastname: Drachenberg
authors.forename: Jinny S
authors.initials: JS
authors.lastname: Ha
authors.forename: Elbert E
authors.initials: EE
authors.lastname: Vaca
authors.forename: Steven T
authors.initials: ST
authors.lastname: Shipley
authors.forename: John C
authors.initials: JC
authors.lastname: Papadimitriou
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Bartlett
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Rodriguez
authors.forename: Rolf N
authors.initials: RN
authors.lastname: Barth
mesh_terms: D000818:Animals; D001706:Biopsy; D002908:Chronic Disease; D054445:Facial Transplantation / Q000009:adverse effects*; D005260:Female; D006084:Graft Rejection / Q000473:pathology*; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D051880:Receptors, Notch / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D007518:Isoantibodies; D051880:Receptors, Notch