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 NeuNAcα2-3Gal, as found in sialyllactose, synthetic sialyl(s) Lewis(Le)x and sLea, sialyllactosamine, sialyl-fucosyllactose, and nonfucosylated sLea, constitutes the minimal epitope for these CAs, implicating that these autoantibodies could be able to bind this domain in sLex and sLea 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 sLea parallels that of sLex determinant as detected by mouse monoclonal antibodies (MoAbs), especially MoAb KM-93. It is also found on epithelial malignant cells bearing both sLex and sLea. 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-sLex MoAb, CSLEX-1, and KM-93. Moreover, CAGAS binds soluble cancer-associated mucins bearing sLex and sLea 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.
DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma
