Evidence for Humoral Rejection of a Pancreatic Islet Graft and Rescue with Rituximab and IV Immunoglobulin Therapy

We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti‐CD20 monoclonal antibody and IV immunoglobulins. A 51‐year‐old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low‐dose insulin therapy. Luminex® screening and single‐antigen assays then revealed the presence of both nondonor‐specific and donor‐specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody‐mediated rejection of the islet allograft, treatment with anti‐CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex® tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin‐free. Rituximab and IV immunoglobulin used for the treatment of humoral pancreatic islet rejection were associated with recovery of islet function.