Effect of IVIG administration on complement activation and HLA antibody levels

The objective of the present study was to determine if there are changes on complement (C) activation and concentration of HLA antibodies (Abs) in patients treated with intravenous immunoglobulin (IVIG). The patients evaluated were given IVIG as treatment of Ab-mediated rejection or desensitization. The patients' sera obtained before and after IVIG administration were tested for their effects on the deposition of both IgG (HLA Abs) and C3b (C activation) as measured by flow cytometry on T cells. IVIG consistently inhibited C activation when measured shortly after IVIG infusion but returned to the initial levels at 2-4 weeks, when total serum IgG also returned to pre-infusion levels. C inhibition was more pronounced with higher IVIG doses and the degree of inhibition was inversely proportional to the HLA Ab concentrations. IVIG did not block the binding of HLA Abs immediately after administration, although levels were slightly but consistently lower after several monthly IVIG infusions. The data show that C inhibition by IVIG is short-lived and that IVIG induces only a mild reduction of HLA Abs, seen not immediately but after months of treatment. These results may explain the inconsistent results of IVIG to achieve desensitization.