title: Transplanted human pancreatic islets after long-term insulin independence.
abstract: Long-term insulin independence after islets of Langerhans transplantation is rarely achieved. The aims of this study were to identify the histological and immunological features of islets transplanted in a type 1 diabetic patient who died of a cerebral hemorrhage after >13 years insulin independence. Islets were pooled from two donors with respectively one and five HLA mismatches. Insulin-positive islets were found throughout the right and left liver, and absent in the pancreas. Two- and three-dimensional analysis showed that islets lost their initial rounded and compact morphology, had a mean diameter of 136 μm and were constituted of an unfolded epithelial band of 39.1 μm. Leukocyte phenotyping showed no evidence of a tolerogenic environment in the islet-containing portal spaces. Finally, HLA typing of microdissected islets showed HLA from the best matched donor in all 23 microdissection samples, compared to 1/23 for the least matched donor. This case report demonstrates that allogeneic islets can survive over 13 years while maintaining insulin independence. Allogeneic islets had unique morphologic features and implanted in the liver regardless of their size. Finally, our results suggest that, in this case, rejection had been prevalent over autoimmunity, although this hypothesis warrants further investigation.
authors: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.|Division of Clinical Immunology and Allergology, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: Y D
authors: YD
authors: Muller
authors: Centre for Infection and Inflammation Research, Faculty of Health, University of Copenhagen, Denmark.
authors: S
authors: S
authors: Gupta
authors: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: P
authors: P
authors: Morel
authors: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: S
authors: S
authors: Borot
authors: National Reference Laboratory for Histocompatibility, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: F
authors: F
authors: Bettens
authors: Division of Clinical Immunology and Allergology, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: M E
authors: ME
authors: Truchetet
authors: Division of Clinical Immunology and Allergology, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: J
authors: J
authors: Villard
authors: Division of Clinical Immunology and Allergology, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: J D
authors: JD
authors: Seebach
authors: Centre for Infection and Inflammation Research, Faculty of Health, University of Copenhagen, Denmark.
authors: D
authors: D
authors: Holmberg
authors: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: C
authors: C
authors: Toso
authors: Department of Pathology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: J A
authors: JA
authors: Lobrinus
authors: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: D
authors: D
authors: Bosco
authors: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors: T
authors: T
authors: Berney
mesh_terms: D000328:Adult; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005260:Female; D006680:HLA Antigens / Q000737:chemistry; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D007107:Immune System; D007328:Insulin / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D016030:Kidney Transplantation / Q000379:methods; D007962:Leukocytes / Q000166:cytology; D008099:Liver / Q000473:pathology; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D059811:HLA-DRB1 Chains; D007328:Insulin