COMPLEMENT ACTIVATION DURING TRYPTOPHAN IMMUNOADSORPTION TREATMENT

Antibodies against human lymphocyte antigens (HLA) are frequently seen among patients undergoing repeated renal transplantations. Graft surv ival can be improved by eliminating these antibodies by plasmapheresis before transplantation. In this study, we have tried a new extracorpo real procedure to remove the anti-HLA antibodies. An immunoadsorption column (IM-TR) with a matrix of polyvinyl alcohol (PVA) gel conjugated with a hydrophobic amino acid tryptophan was utilized. Previous resul ts have shown that repeated IM-TR treatments are at least equally effe ctive as plasmapheresis in reducing levels of specific immunoglobulins in treated patients. In this study, 7 HLA-immunized patients were tre ated before renal transplantation. Each patient was subjected to a tot al of 12 treatment sessions divided into 3 sessions per week. After ea ch treatment session, the reduction of the immunoglobulins was less th an what has been reported for plasmapheresis. This suggests that mecha nisms other than immunoglobulin depletion are involved in the reductio n of the total immunoglobulin levels. The IM-TR treatment resulted in a strong complement activation triggered by the alternative pathway. S ince the adsorbed plasma was returned to the patient, exceedingly high levels of the activation fragment C3d (C3dg) were found in plasma dur ing and after the treatment. We conclude that the extensive generation of C3dg may be one of the factors that plays a role in the reduction of the antibody levels since the C3dg fragment has been shown to down- regulate the immune response.