Acute cellular rejection of a pancreatic islet graft and rescue by steroid therapy: study of microparticles release in peripheral blood

L. Kessler¹, F. Toti², H. Egelhofer³, M.J. Richard³, M. Greget⁴, N. Khamakhem², F. Moreau¹, P.Y. Benhamou⁵, F. Bayle⁶, T. Berney^7
1 University Hospital, Diabetology, Strasbourg, France; ² Laboratory of vascular biology, Strasbourg, France; ³ Therapy cellular Unit, EFS- CHU Rhône Alpes, Grenoble, France; ⁴ University Hospital, Radiology, Strasbourg, France; ⁵ University Hospital, Diabetology, Grenoble, France; ⁶ University Hospital, Nephrology, Grenoble, France; ⁷ Cell isolation and transplantation center, Geneve, Switzerland

We describe the decline of islet function in an islet transplant recipient due to acute cellular rejection, and the graft recovery after steroid bolus therapy.

A 43 year-old woman with type 1 diabetes received one intraportal islet infusion. Immunosuppession was based on tacrolimus and mycophenolate mofetil with thymoglobulin and etanercept induction. Immedialty after islet transplantation, C-peptide levels increased to 1.2ng/ml. One month after transplantation, a peak of post prandial glucose over 11mmol/L was observed with a C-peptide drop to 0.3ng/ml. Anti--HLA antibodies by the Luminex technique remained negative for HLA class I and II. No islet auto antibodies against GAD 65 or IA2 were detected. In the absence of an identified cause of islet loss, a diagnosis of acute cellular islet rejection was brought up and a treatment with steroid boluses was initiated for 6 days. Four days after steroid therapy, C-peptide levels increased back to1.3ng/ml. The rescue of islet function by steroid bolus therapy strongly suggests acute cellular rejection of the islet graft. In addition, peripheral microparticles (MPs; plasma membrane fragments shed from apoptotic cells) were measured in the blood. MPs levels increased from 3.1 to 9.8 nM/ phosphatidyl equivalent (Pser-EQ) after the drop of C-peptide levels and returned to 2.5 nM/Pser-EQ after steroid therapy.

Conclusion: An abrupt decline of islet function, without HLA sensitization, in the early period after islet transplantation suggests acute cellular rejection of the islet graft. Steroid bolus therapy can salvage a rejected islet graft when administered in due time.