Human IgE responses to Schistosoma mansoni and resistance to reinfection

Abstract

Schistosoma mansoni infected Kenyan patients were treated and the intensities of their reinfections were followed over the next two years. In addition, their pre- and six month post-treatment serum levels of IgG1-4, IgM, and IgE, specific for schistosomula, egg and adult worm, were measured in ELISA. No reinfection took place before six months post-treatment. Reinfection intensities varied with age; the younger children becoming reinfected at significantly higher intensities than older individuals. When antibody and reinfection levels were compared, only the six month post-treatment IgE response against adult worm correlated negatively with intensities of reinfection and, therefore, was predictive of resistance or immunity to reinfection. IgE and IgG specific Western Blots were carried out. The adult worm antigens recognized by IgE were restricted compared with the IgG responses of the same patients, although no individual antigen was uniquely recognized by the IgE isotype. A dominant 22 kDa antigen was recognized by most but not all high IgE responders. Patients with IgE responses against this antigen suffered significantly lower subsequent levels of reinfection, compared with non-responders. A monospecific rabbit antiserum against the 22 kDa adult worm antigen showed that this antigen is specifically located in the tegument of the adult worm and of 'lung' and 'liver' stage schistosomula, but is absent from the early 'skin' schistosomula. It is possible that this antigen is a target for human IgE mediated immune effector mechanisms active against the post skin stage schistosomula and that this is boosted by the death of adult worms.

Human Immune Responses toSchistosoma mansoniVaccine Candidate Antigens

“…Specific IgE, interacting with eosinophils and phagocytic cells, has been demonstrated to be effective in schistosomula destruction in vitro (6-8, 10, 12, 13, 15) and may be an important immune defense mechanism in the skin, where these cell types are found at the time of cercarial penetration. The majority of studies done with subjects from areas of endemicity support a role for IgE in resistance to S. mansoni infection (22,24,25,28,56,57). In the present study, the levels of SWAP-specific IgE were not correlated with infection levels.…”

“…Although human immune responses to S. mansoni have been studied extensively, the mechanism by which humans resist schistosome infection are still unclear. Data from two different research groups in areas of endemicity in Kenya and Brazil have shown an association between resistance to reinfection and high levels of specific IgE and high IgE-to-IgG4 ratios (22,24,25,28,56,57). Other studies in two areas of endemicity in Minas Gerais, Brazil, have described subjects who exhibit complete resistance to infection (16).…”

“…Immunological studies of subjects from areas of endemicity have demonstrated a naturally occurring resistance to reinfection (4, 19, 22-25, 27, 28). Both high levels of specific immunoglobulin E (IgE) in sera and gamma interferon (IFN-␥) in antigen-stimulated peripheral blood mononuclear cell (PBMC) cultures were associated with resistance to reinfection (1,22,24,25,27,28,56,57). These data suggest the participation of immunological mechanisms in human resistance to Schistosoma mansoni infection, with mixed cellular and humoral responses.…”

CD23-Bound IgE Augments and Dominates Recall Responses through Human Naive B Cells

“…H igh levels of serum parasite-specific IgE are associated with resistance to human schistosomiasis, but the functional significance is undefined (1)(2)(3)(4). Indeed, the bona fide roles of IgE in the human immune system remain elusive.…”

The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium

“…One such pattern is the distribution of immune responses across different ages in a host population. For both Schistosoma mansoni and S. haematobium responses directed against egg antigen, levels of IgE have been shown to increase with age, those of IgA, IgM and IgG2 have been shown to decrease with age, while levels of IgG1 and IgG3 have been shown to either increase or decrease (Demeure et al 1983, Butterworth et al 1988, Hagan et al 1991, Dunne et al 1992a,b, Grogan et al 1996, Ndhlovu et al 1996, Mutapi et al 1997, Webster et al 1997. The explanations for these patterns have been controversial.…”