Abstract
SummaryBackgroundSerum inhibition of allergen‐specific IgE has been associated with competing IgG4 and non‐specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth‐associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low‐income countries.MethodsAmong community residents of Ugandan rural Schistosoma mansoni (Sm)–endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non‐asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)–specific, Schistosoma egg antigen (SEA)–specific and allergen (house dust mite [HDM] and German cockroach)–specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural‐urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma.ResultsTotal IgE, total IgG4 and SWA‐, SEA‐ and allergen‐specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen‐specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma‐specific IgG4, allergen‐specific IgG4/IgE ratios and total IgE/allergen‐specific IgE ratios. Asthmatic schoolchildren, compared with non‐asthmatic controls, had significantly higher levels of total and allergen‐specific IgE, but lower ratios of allergen‐specific IgG4/IgE and total IgE/allergen‐specific IgE.Conclusions and clinical relevanceOur immuno‐epidemiological data support the hypothesis that the IgG4–IgE balance and the total IgE–allergen‐specific IgE balance are more important than absolute total, helminth‐ or allergen‐specific antibody levels in inhibition of allergies in the tropics.
Highlights
Chronic helminth infection is associated with elevated serum IgG4 levels,[15] and serum inhibition of helminth-specific IgE has been associated with competing IgG4 in a Schistosoma mansoni (Sm)-endemic setting.[16]
Several human studies have suggested that helminth-induced IgG4 is important in protection against allergy: among school-age children in rural Ecuador, Ascaris-specific IgG4 was inversely associated with allergen skin prick test (SPT) reactivity;[2] in a Sm-endemic Ugandan rural setting, we observed an inverse association between house dust mite‐specific IgG4/IgE ratios and reported recent wheeze.[17]
Antibody measurements were conducted in a subset of randomly selected samples per study: 791, 1320 and 406 plasma samples from the rural survey, urban survey and asthma case-control study, respectively, were included in assessment of at least one of total, Schistosomaor allergen-specific IgE or IgG4
Summary
Several immuno-epidemiological studies have shown that helminth infections are associated with protection against allergy-related conditions,[1,2,3,4,5,6,7,8,9] and highlighted the potential role of helminths in rural-urban differences in prevalence of allergy-related diseases in the tropics.[10,11] We have previously shown that maternal hookworm infection modifies risk factors for childhood eczema, implying that early-life exposure to helminths may establish protection against allergy-related diseases.[12]. Antibody-mediated immune mechanisms of protection are less understood compared to cell-mediated mechanisms: current theories involve helminth-induced immunoglobulin (Ig) G4 and polyclonally-stimulated IgE. By inducing high levels of interleukin (IL)-10, helminths can promote immunoglobulin class switching to IgG4. Chronic helminth infection is associated with elevated serum IgG4 levels,[15] and serum inhibition of helminth-specific IgE has been associated with competing IgG4 in a Schistosoma mansoni (Sm)-endemic setting.[16] Several human studies have suggested that helminth-induced IgG4 is important in protection against allergy: among school-age children in rural Ecuador, Ascaris-specific IgG4 was inversely associated with allergen skin prick test (SPT) reactivity;[2] in a Sm-endemic Ugandan rural setting, we observed an inverse association between house dust mite‐specific IgG4/IgE ratios and reported recent wheeze.[17]
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