Unexpected suppression of anti-Fy^a and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin

BACKGROUND: Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti-D in D– mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG-induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316-22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β-1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ-1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis.

STUDY DESIGN AND METHODS: Red blood cells and serum were analyzed using saline-tube indirect antiglobulin test methods. RhIG (RhoGAM) was administered after each amniocentesis performed at 28, 31, and 36 weeks' gestation.

RESULTS: A group A, D–(cde), K+, Fy(a−b+), MNs, Jk(a+b+) mother with no detectable anti-D had an anti-Fy^a titer of 4096 before RhIG but only 256 after RhIG. Mother gave birth to a group O, D–(cde), Fy(a+b+) healthy baby boy having a weak-positive direct antiglobulin test with anti-Fy^a eluted from his cells and the titer in the cord serum was 4.

CONCLUSION: This case demonstrates the potential immunosuppressive properties of RhIG for down regulation of a possible clinically significant alloantibody, not anti-D, where no D+ antigen is in the circulation of the mother. The case illustrates the potential utility for using RhIG to modulate antibody levels in situations other than for classical suppression of anti-D production. Although the mechanism in this case is unknown, TGFβ-1–mediated or antibody-mediated immunosuppression to soluble nonparticulate antigens are possible mechanisms.