Pathology of an islet transplant 2 years after transplantation: evidence for a nonimmunological loss.
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.
Smith
R Neal
RN
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. rnsmith@partners.org
Kent
Sally C
SC
Nagle
Julie
J
Selig
Martin
M
Iafrate
A John
AJ
Najafian
Nader
N
Hafler
David A
DA
Auchincloss
Hugh
H
Orban
Tihamer
T
Cagliero
Enrico
E
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
D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human