The expanding roles of the Sda/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2

BACKGROUND: The histo-blood group antigens are carbohydrate structures present in tissues and body fluids, which contribute to the definition of the individual immunophenotype. One of these, the Sda antigen, is expressed on the surface of erythrocytes and in secretions of the vast majority of the Caucasians and other ethnic groups. SCOPE OF REVIEW: We describe the multiple and unsuspected aspects of the biology of the Sda antigen and its biosynthetic enzyme beta1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) in various physiological and pathological settings. MAJOR CONCLUSIONS: The immunodominant sugar of the Sda antigen is a beta1,4-linked N-acetylgalactosamine (GalNAc). Its cognate glycosyltransferase B4GALNT2 displays a restricted pattern of tissue expression, is regulated by unknown mechanisms - including promoter methylation, and encodes at least two different proteins, one of which with an unconventionally long cytoplasmic portion. In different settings, the Sda antigen plays multiple and unsuspected roles. 1) In colon cancer, its dramatic down-regulation plays a potential role in the overexpression of sialyl Lewis antigens, increasing metastasis formation. 2) It is involved in the lytic function of murine cytotoxic T lymphocytes. 3) It prevents the development of muscular dystrophy in various dystrophic murine models, when overexpressed in muscular fibers. 4) It regulates the circulating half-life of the von Willebrand factor (vWf), determining the onset of a bleeding disorder in a murine model. GENERAL SIGNIFICANCE: The expression of the Sda antigen has a wide impact on the physiology and the pathology of different biological system