title: Composite tissue allotransplantation: classification of clinical acute skin rejection.
abstract: BACKGROUND
  Composite tissue allotransplantation (CTA) is a recently introduced option for limb replacement and reconstruction of other nonreconstructible tissue defects. As with recipients of other allotransplants, CTA recipients can experience rejection episodes that are presumed to be mediated by immune mechanisms similar to those affecting solid organ grafts. However, a systematic examination of this process has not been performed, and there are no standardized criteria for the description of severity or type of rejection
  
  
  METHODS
  We collected biopsies from human limb allografts and abdominal walls in various stages of rejection for histological and immunohistochemical analysis to formulate a CTA rejection scheme. Biopsies were ranked by severity and reproducibility of the system was tested using a second set of biopsies. Tissue slides were examined blindly by three pathologists and the nonparametric Kendall coefficient of concordance (W) was used to assess the amount of agreement among the pathologists in their classification grades.
  
  
  RESULTS
  Rejection initially appeared as a perivascular infiltrate progressing to involve the dermis. Arteritis was observed only in the medium to large size arteries of the subcutis. Myositis was seen occasionally. Perineural involvement without frank neuritis was present in advanced rejection. The infiltrate was predominantly CD4+ in milder cases and CD8+ in advanced cases. HLA-DR was minimally expressed in keratinocytes even in severe rejection. Kendall's W was 0.9375 (p<or=0.0001).
  
  
  CONCLUSIONS
  Based on this survey, we proposed an initial classification system for acute rejection in the skin of a CTA and demonstrated that this system is easily reproduced by independent pathologists.
authors.affiliation: Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Department of Health and Human Resources, Bethesda, MD 20892-1102, USA. cendalesl@mail.nih.gov
authors.forename: Linda C
authors.initials: LC
authors.lastname: Cendales
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
authors.forename: J Margaret
authors.initials: JM
authors.lastname: Moresi
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
mesh_terms: D000208:Acute Disease; D001167:Arteritis / Q000473:pathology; D005355:Fibrosis / Q000473:pathology; D006084:Graft Rejection / Q000473:pathology*; D006801:Humans; D009336:Necrosis; D016377:Organ Transplantation / Q000145:classification / Q000473:pathology*; D012871:Skin Diseases / Q000473:pathology*; D014184:Transplantation, Homologous / Q000145:classification / Q000473:pathology*