Schistosoma mansoni-specific immune responses and allergy in Uganda.

G Nkurunungi,M Nampijja,E L Webb,J Nassuuna,A M Elliott,R E Sanya,B Walusimbi,J Kabagenyi

doi:10.1111/pim.12506

Abstract

SummaryLow allergy‐related disease (ARD) prevalence in low‐income countries may be partly attributed to helminth infections. In the Schistosoma mansoni (Sm)‐endemic Lake Victoria islands (Uganda), we recently observed positive helminth‐allergy associations, despite low ARD prevalence. To understand how Sm‐induced cytokine and antibody profiles might influence allergic response profiles in this population, we assessed Schistosoma worm (SWA)‐ and egg antigen (SEA)‐specific Th1 (IFN‐γ), Th2 (IL‐5, IL‐13) and regulatory (IL‐10) cytokine profiles (n = 407), and total (n = 471), SWA‐, SEA‐ and allergen (house dust mite [HDM] and cockroach)‐specific (as)IgE and IgG4 profiles (n = 2117) by ELISA. Wheeze was inversely associated with SWA‐specific IFN‐γ (P < .001) and IL‐10 (P = .058), and SEA‐specific IL‐5 (P = .004). Conversely, having a detectable asIgE response was positively associated with SWA‐specific IL‐5 (P = .006) and IL‐10 (P < .001). Total, SWA‐, SEA‐ and allergen‐specific IgE and IgG4 responses were higher among Sm Kato‐Katz positive (SmKK+) and skin prick test (SPT)+ individuals compared to SmKK‐ and SPT‐ individuals. However, total and asIgG4/IgE ratios were lower among SPT+ and wheezing individuals. We conclude that, in this population, helminth‐induced antibody and cytokine responses may underlie individual positive helminth‐atopy associations, while the overall IgG4‐IgE balance may contribute to the low overall prevalence of clinical allergies in such settings.

Highlights

Helminths have a small range of antigens that are strikingly homologous to common allergens.[1]
Emerging epidemiological data on helminth-allergy associations in Uganda reflect the complex interaction between helminths and allergens: while observational analyses in a birth cohort suggested a protective effect of childhood and maternal helminths against childhood eczema[19] that was reversed by maternal anthelminthic treatment,[20] we recently reported positive helminth-allergy associations in a survey conducted in the Schistosoma mansoni (Sm)-endemic Lake Victoria islands, albeit against a backdrop of low allergy-related disease (ARD) prevalence.[21]
Using STATA 13.1 (College Station, Texas, USA), we performed cross-sectional analyses to assess whether Sm Kato-Katz positivity and allergy-related outcomes were associated with antibody and cytokine levels, using the “svy” command to allow for the non-self-weighting cluster survey design

Summary

Introduction

Helminths have a small range of antigens that are strikingly homologous to common allergens.[1] These antigens induce immunoglobulin (Ig) E-mediated effector responses important for protection against helminth infection.[2,3] To survive in the host, helminths modulate this atopic pathway, and this may have a bystander protective effect against allergy-related disease (ARD).[4] While several animal and human studies provide compelling evidence of this protection,[5,6] others suggest that in some circumstances helminths may promote enhanced responses to allergens.[7,8]. Helminth-induced IL-10 may drive immunoglobulin class switching to IgG413,14 which, akin to the Th2 cytokine-induced[15] polyclonally stimulated IgE, may inhibit development of allergen-specific effector responses,[5,16] leading to inverse helminth-allergy associations. Helminth-induced protein-specific IgE may promote strong, cross-reactive helminth- and allergenspecific responses, resulting in positive helminth-allergy associations.[17,18]

Methods

Results

Conclusion