Schistosomiasis is a widespread helminthic disease of humans. The egg granuloma is the primary cause of pathology and morbidity. The immune response to the parasite eggs is normally modulated, down-regulated. Those persons who do not modulate the immune response to the eggs develop, in the case of mansoni and japonica, serious hepatosplenic disease. There is now mounting evidence that modulation in patients may be due to neonatal or in utero exposure to egg antigens or specific anti-idiotypic antibodies. This proposal describes experiments aimed at defining schistosome egg antigens which elicit granuloma formation. We propose to do this by separating saline soluble and urea soluble egg antigens into distinct pI fractions via agarose-isoelectricfocusing. The pI fractions will be covalently coupled to beads and tested in the bead granuloma assay. Granuloma-eliciting pI fractions would then be characterized, including testing for the presence of carbohydrate residues. We will determine the involvement of carbohydrate residues in the granulomatous response.
The specific aims of this proposal are: 1) to test via the bead granuloma assay, the granuloma-eliciting properties of pI fractions of egg antigens; 2) to determine if granuloma-eliciting pI fractions contain carbohydrates, and if so, are these properties altered by de-glycosylation; 3) to test native or de-glycosylated KLH, or Lacto-N-fucopentaose III in the bead granuloma assay; 4) to investigate the cellular involvement in the putative granuloma response to carbohydrate epitopes; 5) to partially characterize the granuloma-eliciting antigens; 6) to isolate individual antigens, peptides, glycans or oligosaccharides and then retest these in the granuloma assay; 7) to test if isolated antigens, peptides, glycans or oligosaccharides sensitize naive mice for hepatic granuloma formation. The proposed research will identify egg antigen(s) which elicit granuloma formation in vivo. Identification of relevant antigen(s) will lead to studies on modulation of the granulomatous response due to in utero or neonatal exposure to these antigens. These experiments could lead to the development of an antipathology vaccine. Additionally, patients responsiveness to candidate egg antigens may allow us to predict which patients are likely to develop serious hepatosplenic disease, and therefore be more aggressive with drug intervention.
