title: Zinc transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant.
abstract: BACKGROUND
  Despite the success rate of solitary pancreas transplantation in type 1 diabetes with preserved kidney function has greatly improved in recent years, a residual proportion of failures persists.
  
  
  METHODS
  With the aim of investigating autoimmunity as an unrecognized cause of graft failure, we measured autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and the recently discovered zinc transporter 8 antigen (ZnT8A) in 25 recipients of technically successful solitary pancreas transplantation.
  
  
  RESULTS
  The overall pancreas graft survival was 92%, 88%, and 80% at 2, 4, and 6 years, respectively. Fourteen patients (56%) had one or more autoantibodies before transplantation, with no effect on subsequent pancreas graft outcome. After transplantation, major autoantibody changes (serum conversion from negative to positive, spreading from one to multiple autoantibodies, or titer increase) were observed in 5 of 25 recipients: in four patients, the autoantibody change was followed by the loss of graft function (95% sensitivity, 80% positive predictive value), with a significantly lower graft survival compared with patients without autoantibodies (P<0.0001). The addition of ZnT8A to GADA and IA-2A increased the number of identified autoantibody changes from three to five of 25 recipients and the number of predicted graft function loss from two to four out of five graft losses.
  
  
  CONCLUSIONS
  Detection of major autoantibody changes after technically successful solitary pancreas transplantation is predictive of subsequent loss of graft function. ZnT8A in addition to GADA and IA-2A are a useful marker to be included in the screening panel of posttransplant immune monitoring.
authors.affiliation: Department of Endocrinology & Metabolism, Cisanello University Hospital, Pisa, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Occhipinti
authors.forename: Vito
authors.initials: V
authors.lastname: Lampasona
authors.forename: Fabio
authors.initials: F
authors.lastname: Vistoli
authors.forename: Elena
authors.initials: E
authors.lastname: Bazzigaluppi
authors.forename: Marina
authors.initials: M
authors.lastname: Scavini
authors.forename: Ugo
authors.initials: U
authors.lastname: Boggi
authors.forename: Piero
authors.initials: P
authors.lastname: Marchetti
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bosi
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000737:chemistry* / Q000276:immunology; D015551:Autoimmunity; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D007107:Immune System; D007515:Islets of Langerhans / Q000166:cytology*; D008297:Male; D016035:Pancreas Transplantation / Q000379:methods*; D012008:Recurrence; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; C096322:ICA512 autoantibody; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D005968:Glutamate Decarboxylase