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.