Natural anti-A and anti-B of the ABO system: allo- and autoantibodies have different epitope specificity.

BACKGROUND

According to Landsteiner's law, alloantibodies are prevalent and autoantibodies are absent in the ABO blood group system. However, one study (Spalter et al., Blood 1999;93:4418-24) has suggested that low-affinity ABO autoantibodies, mitigated by anti-idiotypic immunoglobulins are also prevalent, while another publication (Rieben et al., Eur J Immunol 1992;22:2713-7) shows that humans do not have B-lymphocytes capable of producing immunoglobulin G ABO autoantibodies.

STUDY DESIGN AND METHODS

We used hapten-specific chromatography to isolate allo- and autoantibodies from pools of A or B serum and then characterized the resultant antibodies against a wide range of ABO and related glycoconjugates.

RESULTS

We found that the apparent autoantibodies are directed against blood group A or B disaccharides, without consideration for the presence of fucose, but requiring the absence of elongating sugar X in composition of Gal(NAc)α1-3(Fucα1-2)Galβ1-X-terminated carbohydrate chain. In contrast, ABO alloantibodies required a minimum trisaccharide Gal(NAc)α1-3(Fucα1-2)Gal epitope and recognize the elongated type-specific tetrasaccharides. Furthermore, alloantibodies appear to be a small set of specific yet crossreactive antibodies that detect all backbone types of A or B antigens, rather than being a collection of specific antibodies, each of which detects a different type of A or B antigen.

CONCLUSION

Apparent ABO autoantibodies appear to have no natural human target.