Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not explain the protective effect of helminth infections against atopy.
One hypothesis for the decreased rates of atopy observed among helminth-infected individuals is that parasite-induced polyclonal immunoglobulin E (IgE) out-competes allergen-specific IgE for FcepsilonRI binding on basophils and mast cells. In experiments with fresh blood drawn from filaria-infected patients, we found no association between ratios of polyclonal to Brugia malayi antigen (BmAg)-specific IgE (range, 14:1 to 388:1) and basophil responses to BmAg as measured by histamine release. Using serum samples from a filaria-infected patient who also had dust mite (Dermatophagoides pteronyssinus)-specific IgE antibodies from time points with various ratios of polyclonal to D. pteronyssinus-specific IgE (16:1 to 86:1), we demonstrated that increased ratios of polyclonal to D. pteronyssinus-specific IgE did not attenuate basophil sensitization as measured by D. pteronyssinus-specific histamine release. Suppression of histamine release was likely not observed in either of these sets of experiments because polyclonal to antigen-specific IgE ratios were not sufficiently high, as concurrent passive sensitization of basophil experiments required ratios of polyclonal to antigen-specific IgE of greater than 500:1 to suppress basophil histamine release. Further, the intensity of IgE staining in basophil populations from 20 patients with active filaria infections correlated strongly with total serum IgE levels (rho = 0.698; P = 0.0024) with no plateau in intensity of IgE staining, even though some patients had total IgE levels of greater than 10,000 ng/ml. Our data therefore suggest that in helminth infections (and in filarial infections in particular), the ratios of polyclonal to allergen-specific IgE rarely reach those levels necessary to inhibit allergen-specific IgE-FcepsilonRI binding and to suppress allergen-induced degranulation of mast cells and basophils.
Mitre
Edward
E
Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Center Lane, Room 4/126, National Institutes of Health, Bethesda, Maryland 20892, USA. emitre@niaid.nih.gov
Norwood
Stephanie
S
Nutman
Thomas B
TB
D000818:Animals; D001491:Basophils / Q000502:physiology; D001665:Binding Sites; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D006373:Helminthiasis / Q000276:immunology*; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood / Q000378:metabolism*; D017455:Receptors, IgE / Q000032:analysis / Q000378:metabolism*
D017455:Receptors, IgE; D007073:Immunoglobulin E