The influence of intravenous immunoglobulin treatment on maternal immunity in women with unexplained recurrent miscarriage

PROBLEM: Recently the protective value of high-dose intravenous immunoglobulin (IVIG) in the treatment of unexplained recurrent miscarriage has been reported to be similar to that of conventional immunotherapy with paternal leukocytes. We examined the effect of IVIG treatment on the cellular and humoral level of maternal immunity to demonstrate the possible mechanism by which IVIG might act to prevent recurrence of pregnancy loss. METHOD: Eight patients were treated with a 20- to 25-g dose of IVIG every 2 to 3 wk during their first-trimester pregnancies. The development of anti-idiotypic autoantibodies against maternal T-cell receptors, maternal anti-paternal lymphocyte antibodies detected by flow cytometric crossmatch, and changes of maternal lymphocyte subpopulations were monitored before pregnancy and then weekly during IVIG treatment. RESULTS: Five of eight patients gave birth successfully after IVIG treatment given during the first trimester of pregnancy (success rate: 62.5%). Although we could not demonstrate a general immunological effect of IVIG on maternal immunity in vivo, a few significant changes of immunological parameters were found in some patients. CONCLUSION: Our results suggest that the effect of IVIG on maternal immunity is not a passive increase of blocking antibody including anti-HLA antibody or modification of maternal T-cell subsets but, more likely, a passive increase of anti-idiotypic antibody against anti-HLA antibody or soluble HLA antigens. However, whether the immunomodulating effect of IVIG is related to its possible mechanism to prevent abortion remains unestablished.