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Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil - 30/05/13

Doi : 10.1016/j.jaci.2012.10.043 
Camila Alexandrina Figueiredo, PhD a, b, Maurício Lima Barreto, MD, PhD c, Neuza Maria Alcantara-Neves, MD, PhD b, Laura Cunha Rodrigues, MD, PhD d, Philip John Cooper, MD, PhD e, f, Alvaro A. Cruz, MD, PhD g, Lain Carlos Pontes-de-Carvalho, MD, PhD h, Denise C. Lemaire, PhD b, i, Ryan dos Santos Costa, MS b, Leila D. Amorim, PhD j, Candelaria Vergara, MD, PhD a, Nicholas Rafaels, MS a, Li Gao, MD, PhD a, Cassandra Foster a, Monica Campbell, BS a, Rasika A. Mathias, ScD a, Kathleen C. Barnes, PhD a,
a Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Md 
b Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil 
c Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil 
g ProAR–Núcleo de Excelência em Asma, Universidade Federal da Bahia, Salvador, Brazil 
j Instituto de Matemática, Universidade Federal da Bahia, Salvador, Brazil 
d London School of Hygiene and Tropical Medicine, London, United Kingdom 
e Universidad San Francisco de Quito, Quito, Ecuador 
f Centre for Infection, St George’s, University of London, London, United Kingdom 
h Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz–FIOCRUZ, Salvador, Brazil 
i Departamento de Ciências da Vida, Universidade do Estado da Bahia, Salvador, Brazil 

Corresponding author: Kathleen C. Barnes, PhD, Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD.

Abstract

Background

Helminth infections are associated with protection against allergies. It is postulated that IL-10 production after helminth infection suppresses skin hypersensitivity and increases IgG4 production, protecting against allergies.

Objective

We aimed to determine whether IL10 polymorphisms are associated with helminth infection and the risk of wheeze and allergy.

Methods

Twelve IL10 single nucleotide polymorphisms were genotyped in 1353 children aged 4 to 11 years living in a poor urban area in Salvador, Brazil. Wheezing status, Ascaris lumbricoides and Trichuris trichiura infection, IL-10 production by peripheral blood leukocytes stimulated with A lumbricoides extract, serum total IgE levels, specific IgE levels, skin prick test responses to common aeroallergens, and IgG4 and IgE anti–A lumbricoides antibody levels were measured in all children. Association tests were performed by using logistic or linear regression when appropriate, including sex, age, helminth infection, and principal components for ancestry informative markers as covariates by using PLINK.

Results

Allele G of marker rs3024496 was associated with the decreased production of IL-10 by peripheral blood leukocytes in response to A lumbricoides stimulation. Allele C of marker rs3024498 was negatively associated with helminth infection or its markers. Marker rs3024492 was positively associated with the risk of atopic wheeze, total IgE levels, and skin prick test responses to cockroach.

Conclusions

Our findings suggest that IL10 polymorphisms might play a role in the production of IL-10, helminth infection, and allergy. We hypothesize that polymorphisms related to protection against helminths, which would offer an evolutionary advantage to subjects in the past, might be associated with increased risk of allergic diseases.

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Key words : IL10, polymorphisms, helminth infection, immune modulation, allergy, asthma, Social Changes Asthma and Allergy in Latin America

Abbreviations used : CEU, DAG, LD, SNP, SPT, YRI


Plan


 Supported by the Wellcome Trust, UK; the HCPC Latin America Excellence Centre Programme, Ref 072405/Z/03/Z; the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico–CNPq; and the David G. Marsh Award. K.C.B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program.
 Disclosure of potential conflict of interest: M. L. Barreto has received grants from the Wellcome Trust and the National Research Council–Brazil and is employed by the Federal University of Bahia. P. J. Cooper has received grants from the Wellcome Trust and is employed by the Liverpool School of Tropical Medicine. A. A. Cruz serves on boards for Merck Sharp & Dohme and Roche; has consultant arrangements with Mantecorp; receives grants from GlaxoSmithKline; receives payment for lectures from Merck Sharp & Dohme; has received travel/accommodations/meeting expenses from Merck Sharp & Dohme and Novartis; and has conducted clinical trials for AstraZeneca, Novartis, TAKEDA, Eurofarma, GlaxoSmithKline, and Genentech. L. C. Pontes-de-Carvalho is employed by the Ministry of Health, Brazil. C. Vergara, C. Foster, M. Campbell, and R. A. Mathias are employed by Johns Hopkins University and have received grants from the National Institutes of Health. K. C. Barnes serves on boards for Genentech; has consultant arrangements with Sanofi-Aventis and Sirius Genomics; is employed by Johns Hopkins University; has received grants from the National Institutes of Health/National Heart, Lung, and Blood Institute; has received payment for lectures from the “Evolution and Diseases of Modern Environments” Symposium, the Cincinnati Children's Hospital Medical Center Allergy Conference, the 50th Annual Swineford Allergy Conference, and the American Academy of Allergy, Asthma & Immunology; and receives royalties from Up-To-Date. The rest of the authors declare that they have no relevant conflicts of interest.


© 2012  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 131 - N° 6

P. 1683-1690 - juin 2013 Retour au numéro
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