Does an alloimmune response to strong immunogenic red blood cell antigens enhance a response to weaker antigens?

It has been suggested that an immune response against the high immunogenic D antigen also augments the immune response to less immunogenic red blood cell (RBC) antigens. Based on the high antibody frequency, E and K antigens can also be regarded as strong immunogens. The question is whether the immunization against E and K antigens also enhances the formation of other antibody specificities. This question is in particular relevant for patients who are currently transfused with RH- and/or K-matched RBCs.

A retrospective multicenter study analyzed FY, JK, and MNS antibodies alone and in combination with anti-E and/or anti-K. Analysis was performed for primary and subsequent antibody responses.

In the cohort analyzed, 5016 patients possessed 5981 antibodies. Antibodies directed to multiple blood group systems were present in 606 of the 779 (78%) patients with multiple antibodies. In 88 of 1270 (6.9%) patients, FY, JK, and/or MNS antibodies appeared simultaneous with anti-E and/or anti-K during a primary antibody response after transfusion. Patients formed antibodies to antigens in the FY, JK, and MNS systems equally often as first antibodies followed by anti-E or anti-K than as second antibodies after anti-E or anti-K were already present. Patients with anti-E and/or anti-K or with antibodies to antigens in the FY, JK, and/or MNS systems equally often formed additional antibodies during a second antibody response.

An immune response against allogeneic RBC antigens defines good responders who readily form antibodies against other antigens. No support was found that the response against strong RBC antigens also enhances the formation against weaker antigens.