title: Evaluation of C4d staining in liver and small intestine allografts.
abstract: BACKGROUND
  Antibody-mediated humoral rejection in kidney and heart allografts is well recognized and is often associated with poor outcome. C4d deposition in allograft biopsy specimens occurs at sites of antibody-mediated complement activation and has become one of the histopathologic criteria for diagnosis of humoral rejection in the kidney and the heart.
  
  
  OBJECTIVE
  To study immunohistochemical C4d staining as a potential diagnostic marker in liver and small intestine allograft biopsy specimens.
  
  
  METHODS
  Thirty-six small intestine and 71 liver specimens, including native specimens, allografts with and without histologic features of acute cellular rejection, and explants, were stained with antisera to C4d using an immunohistochemical method on formalin-fixed, paraffin-embedded tissue.
  
  
  RESULTS
  In small intestine, C4d labeled capillaries in 27% of cases with no evidence of rejection, 36% of cases with evidence of acute rejection, and 2 (28%) of 7 specimens of native normal small intestine. In liver allograft biopsy specimens, C4d stained endothelium of veins, arteries, and/or sinusoids in 2 (8%) of 25 cases of acute rejection with central vein involvement; C4d staining was negative in biopsy specimens with no evidence of rejection. C4d stained the endothelium in a subset of explanted liver allografts with ductopenic rejection or chronic vascular rejection and strongly stained 1 explant with features of hyperacute rejection.
  
  
  CONCLUSIONS
  The clinical utility of C4d staining in solid organ transplantation may vary by organ. Our data show C4d is unlikely to have utility in small intestine allograft biopsy specimens; however, further study in liver allografts, in conjunction with donor-specific antibody testing, is warranted.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, Calif, USA. mltroxell@yahoo.com
authors.forename: Megan L
authors.initials: ML
authors.lastname: Troxell
authors.forename: John P
authors.initials: JP
authors.lastname: Higgins
authors.forename: Neeraja
authors.initials: N
authors.lastname: Kambham
mesh_terms: D000208:Acute Disease; D001706:Biopsy; D001808:Blood Vessels / Q000378:metabolism; D002908:Chronic Disease; D015935:Complement C4b / Q000378:metabolism*; D006084:Graft Rejection / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007106:Immune Sera; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards; D007421:Intestine, Small / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D010446:Peptide Fragments / Q000378:metabolism*; D013194:Staining and Labeling / Q000592:standards; D014184:Transplantation, Homologous
chemical_list: D007106:Immune Sera; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d