Thoughts on why anti-G does NOT appear to protect against the development of anti-D

A colleague in the Greater Cinncinnati area wonders about the following scenario: A pregnant woman's serum demonstrates anti-G. Since D+G- cells are very rare, in all probability her fetus, if Rh positive, would most likely be D+G+. Assuming that her fetus is G+, what is the reason that her anti-G would not provide the same if not better protection against the development of anti-D, compared to a limited dose of injected anti-D?

The above scenario was considered by W. John Judd, FIBMS, MIBiol Professor of Immunohematology Department of Pathology, University of Michigan Medical Center (attribution used with permission). He offers the following opinion as to why the above described pregnant woman should still receive RhIG immunoprophylaxis.

John states that he finds the fact that RhIG does not afford protection against G alloimmunization to be fascinating, to say the least. Here are his exact words (verbatim): "My assumption that it doesn't stems from cases in which we find anti-G in women who have received RhIG therapy at the appropriate times. I DON'T consider these to be RhIG failures, since anti-D is absent, as determined by negative reactions with DIIIb RBC's. If anti-D (RhIG) does not afford protection against G, why should anti-G prevent formation of anti-D, anymore than anti-K affords protection against D? While both G and D are present on RhD, G is at SER-103 on the 2nd extracellular loop, while most D epitopes are confined to the 3rd, 4th and 6th extracellular loops. In a 3-dimensional model, loops 3, 4 and 6 are adjacent to each other, while loop 2 is between loops 1 and 5 (see page 220 of Human Blood Groups, ed. 2, by Geoff Daniels). It is therefore likely that RhIG does not bind to loop 2, where G resides. Anti-G should be suspected when the titer vs. r'r cells is equal to or higher than the titer vs. R2R2 cells. In the absence of DIIIb cells, the recommendation is to treat as though the antibody is anti-G, and give the woman the required doses of RhIG."

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