title: Immunodiagnostically applicable monoclonal antibodies to the circulating anodic antigen of Schistosoma mansoni bind to small, defined oligosaccharide epitopes.
abstract: Gut-associated glycoproteins constitute a major group of the circulating excretory antigens produced by human Schistosoma species. The O-glycans of the relatively abundant circulating anodic antigen (CAA) from S. mansoni carry long stretches of unique -->6(GlcA beta 1-->3)GalNAc beta 1--> repeats. Specific anti-carbohydrate monoclonal antibodies (mAbs) are essential tools for the immunodiagnostic detection of CAA in the serum or urine of Schistosoma-infected subjects. In order to define the epitopes recognised by these anti-CAA mAbs, we screened a series of protein-coupled synthetic di- to pentasaccharide building blocks of the CAA polysaccharide for immunoreactivity, using ELISA and surface plasmon resonance spectroscopy. It was shown that anti-CAA IgM mAbs preferentially recognise -->6(GlcA beta 1-->3)GalNAc beta 1--> disaccharide units. Interestingly, no mouse anti-CAA mAbs of the IgG class were found that bind to the synthetic epitopes, although many of the IgG mAbs tested do recognise native CAA in a carbohydrate-dependent manner. In addition, both IgM and IgG class antibodies could be detected in human infection sera using the synthetic CAA fragments. These synthetic schistosome glycan epitopes and their matching set of specific mAbs are useful tools that further the development of diagnostic methods and are helpful in defining the immunological responses of the mammalian hosts to schistosome glycoconjugates.
authors.affiliation: Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Vermeer
authors.forename: G J
authors.initials: GJ
authors.lastname: van Dam
authors.forename: K M
authors.initials: KM
authors.lastname: Halkes
authors.forename: J P
authors.initials: JP
authors.lastname: Kamerling
authors.forename: J F G
authors.initials: JF
authors.lastname: Vliegenthart
authors.forename: C H
authors.initials: CH
authors.lastname: Hokke
authors.forename: A M
authors.initials: AM
authors.lastname: Deelder
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000947:Antigens, Helminth / Q000097:blood / Q000276:immunology* / Q000652:urine; D002240:Carbohydrate Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D006023:Glycoproteins / Q000097:blood / Q000276:immunology* / Q000652:urine; D015801:Helminth Proteins / Q000097:blood / Q000276:immunology* / Q000652:urine; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000175:diagnosis / Q000469:parasitology; D020349:Surface Plasmon Resonance
chemical_list: D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D006001:Glycoconjugates; D006023:Glycoproteins; D015801:Helminth Proteins; D009844:Oligosaccharides; C090907:circulating anodic antigen, Schistosoma mansoni