title: Pathology of an islet transplant 2 years after transplantation: evidence for a nonimmunological loss.
abstract: BACKGROUND
  We report the immunological and pathological findings of a 52-year-old woman, who died two years after the second of two islet transplants performed using the Edmonton protocol. After each islet transplant, she gradually lost insulin independence while maintaining low levels of C-peptide secretion.
  
  
  METHODS
  A complete autopsy was performed including pathological and immunohistochemical analysis of hepatic allogeneic islets and native pancreatic islets to identify rejection or autoimmunity. Elispots assays for allogeneic sensitization and autoantibody assays for autoimmunity were performed antemortem after her islet transplantations to test in vitro for evidence of allogeneic sensitization or autoimmunity.
  
  
  RESULTS
  The cause of death was a hypertensive stroke. Small numbers of islets without inflammation were identified within portal venules and stained with insulin. The atrophic pancreas contained small numbers of islets, which stained for insulin, and lacked any inflammation within or adjacent to the islets. In vitro assays for alloantibodies were negative, and Elispots assays failed to identify allogeneic sensitization. In vitro assays for diabetic associated autoantibodies did not identify autoimmune resensitization. The allografted kidney showed only early changes of recurrent diabetic nephropathy, and no evidence of rejection.
  
  
  CONCLUSIONS
  In summary, no evidence was found to support an immunological basis (either allo or autoimmunity) for the slow loss of intrahepatic islets, which may, therefore, be related to nonimmunological anatomic and physiological abnormalities of islets infused into the portal veins or to drug toxicity.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. rnsmith@partners.org
authors.forename: R Neal
authors.initials: RN
authors.lastname: Smith
authors.forename: Sally C
authors.initials: SC
authors.lastname: Kent
authors.forename: Julie
authors.initials: J
authors.lastname: Nagle
authors.forename: Martin
authors.initials: M
authors.lastname: Selig
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Nader
authors.initials: N
authors.lastname: Najafian
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Hugh
authors.initials: H
authors.lastname: Auchincloss
authors.forename: Tihamer
authors.initials: T
authors.lastname: Orban
authors.forename: Enrico
authors.initials: E
authors.lastname: Cagliero
mesh_terms: D001284:Atrophy; D001344:Autopsy; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D017809:Fatal Outcome; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006085:Graft Survival; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016381:Islets of Langerhans Transplantation; D008875:Middle Aged; D011169:Portal Vein / Q000473:pathology; D017211:Treatment Failure
chemical_list: D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human