Cytomegalovirus immune globulin intravenous (human) administration modulates immune response to alloantigens in sensitized renal transplant candidates

One of the important parameters for prolonged waiting time for potential re nal transplant recipients is the presence of preformed antibodies to human leucocyte antigen (HLA) antigens, which is often caused by previous transpl ants, pregnancy or transfusions. In vivo administration of specific and uns elected polyclonal intravenous immunoglobulin (IVIGs) preparations have bee n shown to inhibit anti-HLA alloantibodies in highly sensitized patients. W e sought to determine whether Cytogam (Medimmune Inc., Gaithersburg, MD, US A), a hyperimmune anticytomegalovirus immunoglobulin would (1) effect eithe r in vitro or in vivo alloreactivity, and (2) whether Cytogam therapy could reduce the titre of preformed anti-HLA antibodies in highly sensitized pat ients. Alloreactivity was assessed by mixed lymphocyte reaction (MLR) and c ytotoxic T lymphocyte (CTL) assay. A complement dependent microlymphocytoto xicity assay was done to assess for panel reactive antibody (PRA) status an d the presence of anti-idiotypic antibodies in the Cytogam preparation. The MLR was inhibited by Cytogam in vitro in a dose-dependent fashion ranging from 31-92%. Significant inhibition of the MLR responses was not observed i n recipients who received Cytogam in vivo (50 mg/kg). This could be a resul t of adminstration of a low dose of IVIG. However, CTL activity against the alloantigens in all individuals assessed was significantly inhibited after in vivo administration of Cytogam. Three of five individuals experienced a decrease of 5-32% in the PRA status at 4 weeks post administration of Cyto gam. Cytogam also blocked the anti-HLA antibody titres in a microlymphocyto toxicity assay, suggesting the presence of anti-idiotypic antibodies. Our s tudy was based on a single prophylactic dose of Cytogam (50 mg/kg), however , higher dose administration could be feasible by removing more fluid at di alysis, but should be given intradialytically to avoid volume overload. Ove rall, our results suggest that Cytogam can modulate the in vivo and in vitr o T cell responses against the alloantigens.