Sixty years of antibodies to MNS system hybrid glycophorins: what have we learned?

The MNS system was the second blood group system discovered and at least 16 of the 46 antigens in the MNS system result from genetic recombination, producing a hybrid glycophorin. The incidence of these hybrid glycophorins is highest in East Asian populations. MNS system antigens defined by hybrid glycophorins are immunogenic with alloimmune IgG responses developing after transfusion or pregnancy; with reports originating from Asia, Europe, the Americas, and Australia. This demonstrates the global nature of problems associated with these antibodies. Since the initial report that production of anti-Mi(a) was a cause of hemolytic disease of the fetus and newborn (HDFN), antibodies to antigens defined by hybrid glycophorins have been reported in 27 cases of HDFN (1 fatal) and 8 cases of hemolytic transfusion reaction (HTR) (1 fatal). In at least 40% of these clinical cases, the disease was reported as severe. Hyporegenerative fetal anemia is a common feature of the reported HDFN cases. In all published cases, the causative antibodies were identified by reference laboratory investigative tests following clinical presentation. The failure to detect these antibodies by routine testing highlights the need for consideration of the medical importance of these antibodies when defining antibody screening practices and reagents. The aim of this review is to raise awareness of severe disease caused by antibodies to MNS antigens defined by hybrid glycophorins and, thus, to improve diagnosis and patient management.