title: Kinetics of diabetes-associated autoantibodies after sequential intraportal islet allograft associated with kidney transplantation in type 1 diabetes.
abstract: OBJECTIVE
  Presence or occurrence of pancreas auto-antibodies (aAb) has been shown to be of poor prognosis for islet cell transplantation. The aim of the study was to monitor the kinetics of these aAb after sequential intra-portal islet plus kidney transplantation with pre-Edmonton immunosuppressive regimen in order to determine whether the sequential protocol of transplantation was involved in the occurrence of the immune response.
  
  
  METHODS
  Three patients with IDDM and a previous (IAK) or simultaneous (SIK) kidney transplantation received 3 or 4 ABO compatible islet preparations. Islets (> 8 000 IEQ/kg post culture) were sequentially transplanted within a 12 day period via a per-cutaneous catheter. Immunosuppressive treatment included cyclosporine, steroïds and mycophenolate. Plasma ICAs, GAD 65, IA2 and C peptide (C-p) levels were monitored. Type II HLA phenotype was determined in donors and recipients.
  
  
  RESULTS
  Patient #1 had high anti-GAD levels (26.5 UI/l) before the IAK, while anti-IA2 and ICA levels were low. After the transplantation, C-p levels increased to 4.9 ng/ml at one month before becoming undetectable at 2 months. GAD levels remained high, ICA and IA2 aAb were undetectable. Patients #2 and #3 did not have significant levels of aAb before the islet transplantation. A slight increase in GAD was observed with each islet transplantation, followed by an overt but transient increase in ICA. IA2 levels remained undetectable. Three months after the transplantation and 2 weeks after the increase of ICA, C-p levels, that were >3.4 ng/ml at one month, fell below 0.2 (N: 0.5-2).
  
  
  CONCLUSIONS
  The immunosuppressive regimen used in kidney transplantation is unable to control perfectly anti-pancreas aAb production. Moreover, these results seem to indicate that the benefits of sequential islet transplantation lie more in the increased islet mass they provide than in potential immune benefit.
authors.affiliation: Department of Endocrinology and Metabolism, INSERM ERIT 0106, Lille University Hospital, 6 rue du Pr Laguesse, 59037 Lille Cedex, France. mc-vantyghem@chru-lille.fr
authors.forename: M C
authors.initials: MC
authors.lastname: Vantyghem
authors.forename: I
authors.initials: I
authors.lastname: Fajardy
authors.forename: P
authors.initials: P
authors.lastname: Pigny
authors.forename: C
authors.initials: C
authors.lastname: Noel
authors.forename: J
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: V
authors.initials: V
authors.lastname: Gmyr
authors.forename: B
authors.initials: B
authors.lastname: Vandewalle
authors.forename: C
authors.initials: C
authors.lastname: Proye
authors.forename: F
authors.initials: F
authors.lastname: Pattou
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000601:surgery*; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D007700:Kinetics; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010179:Pancreas / Q000276:immunology*; D011379:Prognosis
chemical_list: D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D002096:C-Peptide; C096322:ICA512 autoantibody; D007166:Immunosuppressive Agents; D007328:Insulin; D007527:Isoenzymes; C024211:islet cell antibody; D016572:Cyclosporine; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D009173:Mycophenolic Acid