Identifying Key Antigens that Drive Antibody-Mediated Regulation of Chronic Schistosomiasis

Abstract

Chronic schistosomiasis is a spectral illness where patients present with either moderate intestinal (INT) schistosomiasis or severe hepatosplenic schistosomiasis (HS). The different clinical manifestations are associated with the immune response in the patient against schistosome eggs that end up lodged in the liver and other organs. Inbred male CBA/J mice infected with Schistosoma mansoni present with two distinct syndromes, moderate splenomegaly syndrome (MSS) and hypersplenomegaly syndrome (HSS); the pathologies of which parallel human INT and HS forms, respectively. Furthermore, antibody with a cross-reactive idiotype (CRI) is produced in MSS mice and INT patients (Montesano, Freeman et al. 1990a) that is absent in HSS mice and HS patients and is believed to play a protective role against severe pathology. Our primary aim was to determine the specific antigens in soluble egg antigen (SEA) that react to protective CRI+ anti-SEA antibodies using the CBA/J mouse model of disease. Using one-dimensional Western blotting, we have shown that the specificities of anti-SEA antibodies present in MSS and HSS forms of schistosomiasis are different. Using two-dimensional differential in-gel electrophoresis, we isolated six spots that were of significant interest as disease-specific candidates and a further six candidates that were infection-specific. Finally, we characterized these antigens using mass spectrometry, where we managed to identify several of these isolated antigens. Our infection-specific antigens can be useful in developing diagnostic tools to identify individuals infected with schistosomiasis, and individuals who are at risk of developing severe disease. Additionally, we found evidence for antigens that are specifically reactive to CRI+ antibodies and these can be used as candidates for the development of a vaccine that can drive the production of these protective antibodies. We also found evidence of CRI- antibody-specific antigens, and further analysis of these antigens may help increase our understanding of severe disease induction in chronic patients. Overall, this study identified several unique candidate antigens that merit further research in developing diagnostic and therapeutic tools, and added to our understanding of helminth interactions in human biology.