title: Evidence for humoral rejection of a pancreatic islet graft and rescue with rituximab and IV immunoglobulin therapy.
abstract: 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.
authors.affiliation: Department of Endocrinology, University Hospital, Strasbourg, France. laurence.kessler@medecine.u-strasbg.fr
authors.forename: L
authors.initials: L
authors.lastname: Kessler
authors.forename: A
authors.initials: A
authors.lastname: Parissiadis
authors.forename: F
authors.initials: F
authors.lastname: Bayle
authors.forename: F
authors.initials: F
authors.lastname: Moreau
authors.forename: M
authors.initials: M
authors.lastname: Pinget
authors.forename: N
authors.initials: N
authors.lastname: Froelich
authors.forename: J-P
authors.initials: JP
authors.lastname: Cazenave
authors.forename: T
authors.initials: T
authors.lastname: Berney
authors.forename: P Y
authors.initials: PY
authors.lastname: Benhamou
authors.forename: D
authors.initials: D
authors.lastname: Hanau
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab