Human IgE Antibody Response to Filarial Worm Infection

Abstract

One-third of all humans, more than 1.5 billion people living in developing countries, are suffering from helminth infection. A vigorous type 2 immune response, characterized by highly elevated levels of IgE, is the hallmark of the host defense against helminth infection. Because the immunogenic triggers and the effects that IgE antibody response has during helminth infection are not well understood, it became common belief that IgE antibodies are nonspecific and nonfunctional. Here we performed an unbiased study of IgE antibodies obtained from subjects infected with filarial nematodes –important parasites of humans - and identified immunodominant antigens with strong diagnostic and vaccine potential. All filarial antigens targeted by IgE were excreted secretory proteins, with a family of previously uncharacterized proteins, the transthyretin-related proteins (TTRs), acting as the strongest inducer of the filaria-specific IgE antibody response. We showed that filaria-specific IgE can function by passively inducing an anaphylactic response in mice. Our results demonstrate how helminth-specific IgE antibodies are likely to function in preventing establishment of infection by inducing a type one hypersensitivity response at the site of new parasite entry. A better understanding of the natural immune targets and purpose of the type 2 immune response/IgE antibody response may help us uncover the origin of modern pathological diseases caused by IgE, a growing epidemic in developed countries.