Paramyosin is a major target of the human IgA response against Schistosoma japonicum

Abstract

Human resistance and susceptibility to schistosomiasis is associated with age and specific antibody isotype responses against worm (SWAP) and egg (SEA) antigens. In a cross-sectional study of 176 individuals infected with Schistosoma japonicum in the Philippines, strikingly similar isotype response patterns against SWAP and SEA was observed when compared to other endemic areas. Interestingly, IgA titres to SWAP correlated with older age among S. japonicum-infected individuals (n = 176, P < 0.01), suggesting a role for this isotype in protective immunity. To identify the molecular targets of human IgA, 17 high-IgA/SWAP responders were identified from the said population. IgA antibodies from the majority (14/17) of these individuals recognized a band of 97 kDa (Sj97), comigrating in immunoblots with the myofibrillar protein paramyosin. The antigen was confirmed as paramyosin by expressed sequence tag (EST)-analysis of four clones obtained by screening an adult S. japonicum cDNA library with pooled IgA antisera and mouse antiparamyosin polyclonal antibodies. The identification of paramyosin as a major target of human IgA raises its potential as a vaccine candidate that targets mucosal immune responses. Since this antigen is exposed on the parasite surface only during the lung stages, we propose that human IgA contributes to parasite attrition during schistosome migration in the lungs.