title: Allergen-specific IgE and IgG4 are markers of resistance and susceptibility in a human intestinal nematode infection.
abstract: IgG4 has been proposed to act as a 'blocking antibody' due to its ability to compete for the same epitopes as IgE thus preventing IgE-dependent allergic responses. IgG4 and IgE are both elevated in helminth infections and strong anti-parasite IgE responses are associated with resistance to infection. We wished to determine the relationship between anti-parasite IgG4 and IgE and Ascaris lumbricoides infection status. We examined anti-parasite responses, including antibody levels to recombinant Ascaris allergen-1A (rABA-1A), a target of serum IgE in endemic populations. Worm burden was indirectly estimated by measuring parasite egg output in a cross-sectional human population (N = 105). Levels of anti-parasite IgG4 and IgE in patients' plasma were quantified by immunoassay. Global anti-parasite antibody responses did not bear any significant relationships with intensity of Ascaris infection. Individuals who had detectable levels of IgE but not IgG4 to rABA-1A (11%) had lower average levels of infection compared with individuals who produced anti-rABA-1A IgG4 (40%) and sero-negative individuals (49%) (P = 0.008). The ratio of IgG4/IgE in rABA-1A responders positively correlated with intensity of infection (P < 0.025). IgG4 levels positively correlated with infection level in younger children (age 4-11) where average levels of infection were increasing (P = 0.038), whereas allergen specific IgE emerged as a correlate of immunity in older children and adults (age 12-36) where infection levels were decreasing (P = 0.048). Therefore, in a gastrointestinal helminth infection, differential regulation of anti-allergen antibody isotypes relate to infection level. Our results are consistent with the concept that IgG4 antibody can block IgE-mediated immunity and therefore allergic processes in humans.
authors.affiliation: School of Biology, University of Nottingham, University Park, UK.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Turner
authors.forename: Helen
authors.initials: H
authors.lastname: Faulkner
authors.forename: Joseph
authors.initials: J
authors.lastname: Kamgno
authors.forename: Malcolm W
authors.initials: MW
authors.lastname: Kennedy
authors.forename: Jerzy
authors.initials: J
authors.lastname: Behnke
authors.forename: Michel
authors.initials: M
authors.lastname: Boussinesq
authors.forename: Janette E
authors.initials: JE
authors.lastname: Bradley
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D001196:Ascariasis / Q000276:immunology*; D017164:Ascaris lumbricoides / Q000276:immunology*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D005243:Feces / Q000469:parasitology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D008875:Middle Aged; D010270:Parasite Egg Count
chemical_list: D000909:Antibodies, Helminth; D015415:Biomarkers; D007074:Immunoglobulin G; D007073:Immunoglobulin E