Suppression of the humoral immune response by mycophenolate mofetil

Background. No conventional immunosuppressive agent preferentially inhibits antibody production. Studies in experimental animals and in human cells in vitro suggested mycophenolate mofetil (MMF) might have such an effect. If this was the case in vivo it could have significant implications in terms of both MMF toxicity and the rational design of immunotherapeutic regimens. Methods. Subjects were renal transplant recipients (25 patients treated with prednisolone, cyclosporine and azathioprine, and 13 treated with prednisolone, cyclosporine and MMF) and 20 normal controls. The three groups received influenza vaccination, and the antibody response to it was measured 4-6 weeks later using a standard haemagglutination assay. Results. MMF profoundly suppressed the humoral immune response to influenza vaccination when added to prednisolone and cyclosporine. This effect could be seen when comparing the rise in the mean titre of antibody after vaccination. It was also reflected in the number of patients mounting responses deemed to be clinically protective by either demonstrating a 4-fold rise in titre or an increase in titre to greater than or equal to 40. Conclusions. Suppression of the humoral immune response by MMF has implications for the design of immunization protocols to protect the immunosuppressed, and raises the possibility that MMF use may be accompanied by more or different infections than complicate more conventional immunosuppression. More importantly, consideration should be given to harnessing the relatively specific effect of MMF on antibody production to treat antibody-mediated diseases.