Anti-Sia-lb (formerly anti-Gd)
cold agglutinins (CAs) recognize sialylated
carbohydrates on both adult and neonate red blood cells (RBCs). RBC CA activity inhibition experiments reported here indicate that the domain NeuNAc alpha2-3Gal, as found in
sialyllactose, synthetic sialyl(s) Lewis(Le)(x) and sLe(a), sialyllactosamine, sialyl-fucosyllactose, and nonfucosylated sLe(a), constitutes the minimal
epitope for these CAs, implicating that these
autoantibodies could be able to bind this domain in
sLe(x) and sLe(a) and related
carbohydrates expressed on nucleated cells and in soluble
cancer-related
mucins. The following data obtained with the previously characterized monoclonal IgMk anti-Sia-lb CA, GAS, show that this is the case. GAS
epitope expression among leukocytes that lack sLe(a) parallels that of
sLe(x) determinant as detected by mouse
monoclonal antibodies (MoAbs), especially MoAb KM-93. It is also found on epithelial malignant cells bearing both
sLe(x) and sLe(a). GAS
epitope on these nucleated cells, (1) like that present on RBC, is abolished by
sialidase, unaffected by
proteases, and inhibited by
sialyllactose; and (2) is overlapping and/or proximal to that recognized by anti-
sLe(x) MoAb, CSLEX-1, and KM-93. Moreover, CAGAS binds soluble
cancer-associated
mucins bearing
sLe(x) and sLe(a) determinants. This binding is inhibited by
sialyllactose and these
mucins inhibit the RBC CA activity of CAGAS. The possible significance of anti-Sia-lb (anti-Gd) CAs as
autoantibodies directed to
carbohydrate ligands of host adhesion molecules that might be receptors of microbial adhesins of some CA-inducing pathogens is discussed.