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. 2021 May;51(5):703-715.
doi: 10.1111/cea.13834. Epub 2021 Feb 5.

Allergen skin test reactivity and asthma are inversely associated with ratios of IgG4/IgE and total IgE/allergen-specific IgE in Ugandan communities

Gyaviira Nkurunungi  1 , Jacent Nassuuna  1 , Harriet Mpairwe  1   2 , Joyce Kabagenyi  1 , Margaret Nampijja  1 , Richard E Sanya  1   3 , Emily L Webb  4 , Alison M Elliott  1   5
Affiliations

Allergen skin test reactivity and asthma are inversely associated with ratios of IgG4/IgE and total IgE/allergen-specific IgE in Ugandan communities

Gyaviira Nkurunungi et al. Clin Exp Allergy. 2021 May.

Abstract

Background: Serum 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.

Methods: Among 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.

Results: Total 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 relevance: Our 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.

Keywords: Schistosoma; IgE; IgG4; allergen; asthma; skin prick test.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Study flow chart
FIGURE 2
FIGURE 2
Associations between antibody ratios and Schistosoma mansoni infection and skin prick test reactivity. Forest plots show geometric mean ratios (GMRs) and 95% confidence intervals (95% CIs) for associations between antibody ratios and (A) current S. mansoni infection and (B, C) allergen skin prick test reactivity. Raw antibody responses were skewed, so log10‐transformed antibody data were used in our linear regression models; we back‐transformed the results to obtain GMRs and 95% CIs. All GMRs and 95% CIs were adjusted for age and sex, and additionally for survey design in the rural and urban surveys. GMRs and 95% CIs for associations with skin prick test reactivity were additionally adjusted for S. mansoni infection status. Red colour denotes associations where GMR and 95% CI >1; blue colour denotes associations where GMR and 95% CI <1, and black colour denotes lack of a significant association. *Antibody levels detected by ELISA. Concentrations are in ng/ml. **Antibody levels detected by ImmunoCAP®. Concentrations are in kU/L
FIGURE 3
FIGURE 3
Asthma case‐control study: associations between asthma and antibody concentrations and ratios. Forest plots show geometric mean ratios (GMRs) and 95% confidence intervals (95% CIs) for associations between asthma and antibody concentrations (A) and ratios (B). Raw antibody responses were skewed, so log10‐transformed antibody data were used in our linear regression models; we back‐transformed the results to obtain GMRs and 95% CIs. All GMRs and 95% CIs were adjusted for age and sex. Red colour denotes associations where GMR and 95% CI >1; blue colour denotes associations where GMR and 95% CI <1, and black colour denotes lack of a significant association. *Antibody levels detected by ELISA. Concentrations are in ng/ml. **Antibody levels detected by ImmunoCAP®. Concentrations are in kU/L. SEA, Schistosoma egg antigen; SWA, Schistosoma adult worm antigen
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