Anti-U alloimmunisation in a pregnant woman from Niger.

Abstract

“U” was the name that Wiener et al.1 gave in 1953 to recall the almost universal distribution of a new antigen that they described. The antigen was identified through the serum of an Afro-American patient who had a fatal transfusion reaction: the serum reacted with the red blood cells of 977 of 989 Afro-American patients and all 1,000 Caucasian-American patients tested. The U antigen belongs to the MNS blood group system, the only, together with the Rh system, to be synthesised starting from two very closely linked loci, GYPA and GYPB, which, together with a third locus, GYPE, form a gene cluster on chromosome 4 (4q28→q31)2–3. The U antigen, together with the S and s antigens, is expressed on glycophorin B (GPB), a red blood cell membrane glycoprotein, coded for by the GYPB locus4–6. The amino acid residues from 33 to 39 are essential for the expression of the U antigen. Its antigenicity is not, however, entirely due to this molecular sequence7. The U antigen is a public antigen, occurring almost universally in Caucasian populations8. In populations belonging to ethnic groups originating from Sub-Saharan Africa, there is a S-s−U− phenotype, found with a frequency that varies from 1% among Afro-Americans up to 35% among the Pygmies of Congo9; the spread of this phenotype among these populations is related to the fact that it hampers the entrance of malaria plasmodia into red blood cells. This phenotype is caused by the lack of glycophorin B. U− subjects are always also S- and s−. In contrast, the lack of S and s antigens is not always associated with an absence of the U antigen from the red blood cell membrane. According to some research, about 51% of S-s− subjects are U+10. In these cases, however, the U antigen is variously altered by rearrangements of the amino acid sequence in the residues from 33 to 39: this is indicated by the notation U+var which stands for a variant of the U antigen. The notation U+var does, therefore, represent a heterogeneous group of molecules from the points of view of both amino acid sequence and antigens, but a group united by the fact of having some epitopes specific to the U molecule from which each variant is derived11. Subjects with the S-s−U+var phenotype produce anti-U antibodies that react with all U+ and with a variable proportion of other U+var, depending on the epitopes expressed on the variant molecule. S-s−U− subjects, on the other hand, produce antibodies that react with all U+ and U+var red blood cells and should, more correctly, be called anti-U/GPB12. While the S-s−U− phenotype is a consequence of a deletion of GYPB, the molecular basis of the S-s−U+var phenotype is a GYPB-like, hybrid gene. Anti-U is the cause of haemolytic disease of the foetus and newborn, as well as of haemolytic transfusion reactions13. This is a rare immunohaematological problem: 24 cases of anti-U immunisation have been reported in the literature, all of which occurred in pregnant women from ethnic groups originating from Sub-Saharan Africa14–27. The severity of the haemolytic disease varies from asymptomatic to fatal, with intrauterine death. Anti-U immunisation causes important diagnostic and transfusional problems, related both to its rarity and to the specific immunohaematological problem of non-Caucasian ethnic groups, a new problem for Italy. Here we report a case of immunisation against the U antigen, which came to our attention at the Service of Immunohaematology and Transfusion Medicine, Careggi (Italy) in 2009.