Does Rh immune globulin suppress HLA sensitization in pregnancy?

How Rh immune globulin (RhIG) prevents sensitization to D antigen is unclear. If RhIG Fc delivers a nonspecific immunosuppressive signal, then RhIG may inhibit sensitization to antigens other than D. HLA antibody prevalence was compared in previously pregnant D- versus D+ women to investigate whether RhIG suppresses HLA sensitization.

In the Leukocyte Antibody Prevalence Study (LAPS), 7920 volunteer blood donors were screened for anti-HLA and surveyed about prior pregnancies and transfusions. A secondary analysis of the LAPS database was performed.

D- women not more than 40 years old (presumed to have received antenatal with or without postpartum RhIG in all pregnancies) had a significantly lower HLA sensitization rate than D+ women (relative risk, 0.58; 95% confidence interval [CI], 0.40-0.83). When stratified by deliveries (one, two, three, or four or more), D- women not older than 40 were HLA sensitized less often than D+ women in every case. In contrast, a clear relationship between D type and HLA sensitization was not seen in older previously pregnant women whose childbearing years are presumed to have preceded the use of routine RhIG prophylaxis. In a multivariable logistic regression model, D- women not more than 40 years old remained significantly less likely to be HLA sensitized compared with D+ women after adjusting for parity, time from last pregnancy, lost pregnancies, and transfusions (odds ratio [OR], 0.55; 95% CI, 0.34-0.88).

Consistent with a nonspecific immunosuppressive effect of RhIG, younger previously pregnant D- women were less likely than previously pregnant D+ women to be HLA sensitized.