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.
Patients and 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).
Conclusion: 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.