THE IMMUNOLOGICALLY REACTIVE O-LINKED POLYSACCHARIDE CHAINS DERIVED FROM CIRCULATING CATHODIC ANTIGEN ISOLATED FROM THE HUMAN BLOOD FLUKE SCHISTOSOMA-MANSONI HAVE LEWIS-X AS REPEATING UNIT

The gut-associated excretory antigen circulating cathodic antigen (CCA ) was isolated by immunoaffinity chromatography from adult Schistosoma mansoni worms, which were collected from infected golden hamsters. Th is antigen is probably involved in protection of the schistosome gut a nd is increasingly used in highly sensitive and specific immunodiagnos tic assays. Amino acid analysis before and after alkaline borohydride treatment of CCA and monosaccharide analysis indicated that CCA is O-g lycosylated mostly via GalNAc-Thr. After reductive alkaline treatment, the O-linked carbohydrate chains were fractionated by gel-permeation chromatography, followed by normal-phase HPLC on LiChrosorb-NH2. Carbo hydrate-positive fractions were investigated by one-dimensional and tw o-dimensional H-1-NMR spectroscopy, fast atom bombardment mass spectro metry and collision-induced-dissociation tandem mass spectrometry. The analyses showed that the low-molecular-mass O-linked oligosaccharide alditols (the minor fraction) consist of disaccharides to hexasacchari des having the Gal beta(1-3)GalNAc-OL core in common. The major carboh ydrate fraction comprises a population of polysaccharides, containing Lewis x repeating units (-3)Gal beta(1-4) [Fuc alpha(1-3)]GlcNAc beta( 1-). CCA-specific monoclonal antibodies and IgM antibodies in patient sera recognized the fucosylated O-linked carbohydrate antigenic struct ures. Since CCA evokes a strong IgM antibody response and carbohydrate structures containing repeating Lewis x units are found on circulatin g neutrophils, it is proposed that the antigenic poly-Lewis x polysacc haride of CCA is involved in the induction of auto-immunity against gr anulocytes, resulting in the mild to moderate neutropenia observed dur ing schistosome infection.