EFFECT OF CYCLOSPORINE-A ON IMMUNOGLOBULIN CLASS IN PATIENTS RECEIVING BLOOD-TRANSFUSIONS

IgG antibodies detected by flow cytometry in sera from potential renal transplant recipients are associated with an increased number of rejection episodes and impaired graft function. Furthermore, cytotoxic antibodies may develop if pre-transplant blood transfusions are given to such patients. We have investigated the effect of cyclosporin A on the development of IgM and IgG antibodies detected by flow cytometry after blood transfusions in 16 previously untransfused dialysis patients. Eight (group 1) received three to five third-party blood transfusions at two weekly intervals and the remaining eight (group 2) received transfusions with concomitant cyclosporin A therapy (10 mg/kg/day). Sera obtained after each transfusion were tested using flow cytometry against lymphocytes from six normal donors. In all 462 serum/cell combinations were tested. Sera from six out of eight patients in group 1 showed IgG antibody activity following blood transfusions and none developed IgM antibodies alone. In contrast IgG antibody activity was detected in one serum sample from only one of the eight patients in group 2 (P < 0.02); a further three patients developed IgM but not IgG antibody activity during the transfusion protocol. IgG antibodies were found in 25/228 serum/cell combinations in group 1 but in 1/234 in group 2 (P < 0.001). The patient in group 2 who developed IgG antibodies in one serum/cell combination was known to have red cell autoantibodies. This IgG activity was removed by red cell absorption, suggesting that the autoreactive red cell antibody cross-reacted with lymphocytes. Cytotoxic antibodies were detected in two serum/cell combinations in group 1 alone. We conclude that the switch from IgM to IgG antibody production is abrogated by cyclosporin A. This may be one mechanism by which cyclosporin A prevents the development of cytotoxic antibodies in potential graft recipients given third-party blood transfusions.