ANTI-SIA-IB (ANTI-GD) COLD AGGLUTININS BIND THE DOMAIN NEUNAC-ALPHA-2-3GAL IN SIALYL LEWIS(X), SIALYL LEWIS(A), AND RELATED CARBOHYDRATES ON NUCLEATED CELLS AND IN SOLUBLE CANCER-ASSOCIATED MUCINS

Anti-Sia-lb (formerly anti Gd) cold agglutinins (CAs) recognize sialyl ated carbohydrates on both adult and neonate red blood cells (RBCs). R BC CA activity inhibition experiments reported here indicate that the domain NeuNAc alpha 2-3Gal, as found in sialyllactose, synthetic sialy l(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 he able to bind this domain in sLe(x) and sLe(a) and related carbohydrates expressed an nu cleated cells and in soluble cancer related mucins, The following data obtained with the previously characterized monoclonal IgMk anti-Sia-l b CA, GAS, show that this is the case, GAS epitope expression among le ukocytes that lack sLe(a) parallels that of sLe(x) determinant as dete cted 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 inhibite d by sialyllactose; and (2) is overlapping and/or proximal to that rec ognized by anti-sLe(x) MoAb, CSLEX-1, and KM-93. Moreover, CAGAS binds soluble cancer-associated mucins bearing sLe(x) and sLe(a) determinan ts. This binding is inhibited by sialyllactose and these mucins inhibi t the RBC CA activity of CAGAS. The possible significance of anti-Sia- Ib (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, (C) 1997 by The American Society oi Hematology.