Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical and Molecular Allergy
Published in: Clinical and Molecular Allergy 1/2011

Open Access 01-12-2011 | Research

Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma

Authors: Supinda Bunyavanich, Erik Melen, Jemma B Wilk, Mark Granada, Manuel E Soto-Quiros, Lydiana Avila, Jessica Lasky-Su, Gary M Hunninghake, Magnus Wickman, Göran Pershagen, George T O'Connor, Scott T Weiss, Juan C Celedόn

Published in: Clinical and Molecular Allergy | Issue 1/2011

Login to get access

Abstract

Background

Allergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.

Objective

To test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.

Methods

We genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.

Results

Across the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.

Conclusions

TSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma.
Appendix
Available only for authorised users
Literature
1.
Meltzer EO, Blaiss MS, Derebery MJ, Mahr TA, Gordon BR, Sheth KK, Simmons AL, Wingertzahn MA, Boyle JM: Burden of allergic rhinitis: results from the Pediatric Allergies in America survey. J Allergy Clin Immunol. 2009, 124: S43-70. 10.1016/j.jaci.2009.05.013CrossRefPubMed
2.
Thomas M, Kocevar VS, Zhang Q, Yin DD, Price D: Asthma-related health care resource use among asthmatic children with and without concomitant allergic rhinitis. Pediatrics. 2005, 115: 129-134.PubMed
3.
Sazonov Kocevar V, Thomas J, Jonsson L, Valovirta E, Kristensen F, Yin DD, Bisgaard H: Association between allergic rhinitis and hospital resource use among asthmatic children in Norway. Allergy. 2005, 60: 338-342. 10.1111/j.1398-9995.2005.00712.xCrossRefPubMed
4.
Bunyavanich S, Soto-Quiros ME, Avila L, Laskey D, Senter JM, Celedon JC: Risk factors for allergic rhinitis in Costa Rican children with asthma. Allergy. 2010, 65 (2): 256-63. Epub 2009 Oct 1. 10.1111/j.1398-9995.2009.02159.xPubMedCentralCrossRefPubMed
5.
Corren J, Manning BE, Thompson SF, Hennessy S, Strom BL: Rhinitis therapy and the prevention of hospital care for asthma: a case-control study. J Allergy Clin Immunol. 2004, 113: 415-419. 10.1016/j.jaci.2003.11.034CrossRefPubMed
6.
Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A: Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002, 3: 673-680. 10.1038/nrm910CrossRefPubMed
7.
Allakhverdi Z, Comeau MR, Jessup HK, Yoon BR, Brewer A, Chartier S, Paquette N, Ziegler SF, Sarfati M, Delespesse G: Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med. 2007, 204: 253-258. 10.1084/jem.20062211PubMedCentralCrossRefPubMed
8.
9.
Ying S, O'Connor B, Ratoff J, Meng Q, Mallett K, Cousins D, Robinson D, Zhang G, Zhao J, Lee TH, Corrigan C: Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J Immunol. 2005, 174: 8183-8190.CrossRefPubMed
10.
Ying S, O'Connor B, Ratoff J, Meng Q, Fang C, Cousins D, Zhang G, Gu S, Gao Z, Shamji B: Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J Immunol. 2008, 181: 2790-2798.CrossRefPubMed
11.
Hunninghake GM, Soto-Quiros ME, Avila L, Kim HP, Lasky-Su J, Rafaels N, Ruczinski I, Beaty TH, Mathias RA, Barnes KC: TSLP polymorphisms are associated with asthma in a sex-specific fashion. Allergy. 2010, 65 (12): 1566-75. 10.1111/j.1398-9995.2010.02415.xPubMedCentralCrossRefPubMed
12.
Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, Gober L, Kim C, Glessner J, Frackelton E: Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet. 2010, 42: 289-291. 10.1038/ng.547PubMedCentralCrossRefPubMed
13.
Mou Z, Xia J, Tan Y, Wang X, Zhang Y, Zhou B, Li H, Han D: Overexpression of thymic stromal lymphopoietin in allergic rhinitis. Acta Otolaryngol. 2008, 1-5.
14.
Miyata M, Hatsushika K, Ando T, Shimokawa N, Ohnuma Y, Katoh R, Suto H, Ogawa H, Masuyama K, Nakao A: Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis. Eur J Immunol. 2008, 38: 1487-1492. 10.1002/eji.200737809CrossRefPubMed
15.
Kamekura R, Kojima T, Koizumi JI, Ogasawara N, Kurose M, Go M, Harimaya A, Murata M, Tanaka S, Chiba H: Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells. Cell Tissue Res. 2009, 338 (2): 283-93. Epub 2009 Sep 9. 10.1007/s00441-009-0855-1CrossRefPubMed
16.
Zhu DD, Zhu XW, Jiang XD, Dong Z: Thymic stromal lymphopoietin expression is increased in nasal epithelial cells of patients with mugwort pollen sensitive-seasonal allergic rhinitis. Chin Med J (Engl). 2009, 122: 2303-2307.
17.
Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, Qin FX, Yao Z, Cao W, Liu YJ: TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med. 2005, 202: 1213-1223. 10.1084/jem.20051135PubMedCentralCrossRefPubMed
18.
Wang YH, Liu YJ: Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin Exp Allergy. 2009, 39: 798-806. 10.1111/j.1365-2222.2009.03241.xPubMedCentralCrossRefPubMed
19.
Seshasayee D, Lee WP, Zhou M, Shu J, Suto E, Zhang J, Diehl L, Austin CD, Meng YG, Tan M: In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. J Clin Invest. 2007, 117: 3868-3878. 10.1172/JCI33559PubMedCentralCrossRefPubMed
20.
Reche PA, Soumelis V, Gorman DM, Clifford T, Liu M, Travis M, Zurawski SM, Johnston J, Liu YJ, Spits H: Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J Immunol. 2001, 167: 336-343.CrossRefPubMed
21.
Pandey A, Ozaki K, Baumann H, Levin SD, Puel A, Farr AG, Ziegler SF, Leonard WJ, Lodish HF: Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat Immunol. 2000, 1: 59-64.PubMed
22.
Park LS, Martin U, Garka K, Gliniak B, Di Santo JP, Muller W, Largaespada DA, Copeland NG, Jenkins NA, Farr AG: Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med. 2000, 192: 659-670. 10.1084/jem.192.5.659PubMedCentralCrossRefPubMed
23.
Li M, Messaddeq N, Teletin M, Pasquali JL, Metzger D, Chambon P: Retinoid × receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin. Proc Natl Acad Sci USA. 2005, 102: 14795-14800. 10.1073/pnas.0507385102PubMedCentralCrossRefPubMed
24.
Meltzer EO, Szwarcberg J, Pill MW: Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway. J Manag Care Pharm. 2004, 10: 310-317.PubMed
25.
Pearce N, Ait-Khaled N, Beasley R, Mallol J, Keil U, Mitchell E, Robertson C: Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007, 62: 758-766. 10.1136/thx.2006.070169PubMedCentralCrossRefPubMed
26.
The Childhood Asthma Management Program (CAMP): design, rationale, and methods. Childhood Asthma Management Program Research Group. Control Clin Trials. 1999, 20: 91-120.CrossRef
27.
Himes BE, Hunninghake GM, Baurley JW, Rafaels NM, Sleiman P, Strachan DP, Wilk JB, Willis-Owen SA, Klanderman B, Lasky-Su J: Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am J Hum Genet. 2009, 84: 581-593. 10.1016/j.ajhg.2009.04.006PubMedCentralCrossRefPubMed
28.
Melen E, Nyberg F, Lindgren CM, Berglind N, Zucchelli M, Nordling E, Hallberg J, Svartengren M, Morgenstern R, Kere J: Interactions between glutathione S-transferase P1, tumor necrosis factor, and traffic-related air pollution for development of childhood allergic disease. Environ Health Perspect. 2008, 116: 1077-1084. 10.1289/ehp.11117PubMedCentralCrossRefPubMed
29.
Moffatt M, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WOCM, : A large-scale, consortium-based genome-wide association study of asthma. N Engl J Med. 2010, 363: 1211-1221. 10.1056/NEJMoa0906312PubMedCentralCrossRefPubMed
30.
Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T, Baena-Cagnani CE, Canonica GW, van Weel C, World Health Organization; GA(2)LEN; AllerGen : Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008, 63: 8-160. 10.1111/j.1398-9995.2007.01620.xCrossRefPubMed
31.
The International HapMap Project. Nature. 2003, 426: 789-796.
32.
Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21: 263-265. 10.1093/bioinformatics/bth457CrossRefPubMed
33.
Harada M, Hirota T, Jodo AI, Doi S, Kameda M, Fujita K, Miyatake A, Enomoto T, Noguchi E, Yoshihara S: Functional analysis of the thymic stromal lymphopoietin variants in human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2009, 40: 368-374. 10.1165/rcmb.2008-0041OCCrossRefPubMed
34.
He JQ, Hallstrand TS, Knight D, Chan-Yeung M, Sandford A, Tripp B, Zamar D, Bosse Y, Kozyrskyj AL, James A: A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness. J Allergy Clin Immunol. 2009, 124: 222-229. 10.1016/j.jaci.2009.04.018CrossRefPubMed
35.
Lange C, DeMeo D, Silverman EK, Weiss ST, Laird NM: PBAT: tools for family-based association studies. Am J Hum Genet. 2004, 74: 367-369. 10.1086/381563PubMedCentralCrossRefPubMed
36.
Laird NM, Lange C: Family-based designs in the age of large-scale gene-association studies. Nat Rev Genet. 2006, 7: 385-394. 10.1038/nrg1839CrossRefPubMed
37.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81: 559-575. 10.1086/519795PubMedCentralCrossRefPubMed
38.
Hunninghake GM, Lasky-Su J, Soto-Quiros ME, Avila L, Liang C, Lake SL, Hudson TJ, Spesny M, Fournier E, Sylvia JS: Sex-stratified linkage analysis identifies a female-specific locus for IgE to cockroach in Costa Ricans. Am J Respir Crit Care Med. 2008, 177: 830-836. 10.1164/rccm.200711-1697OCPubMedCentralCrossRefPubMed
39.
Fisher RA: Statistical Methods for Research Workers. Edinburgh: Oliver and Boyd; 1932.
40.
Almqvist C, Worm M, Leynaert B: Impact of gender on asthma in childhood and adolescence: a GA2LEN review. Allergy. 2008, 63: 47-57.PubMed
41.
42.
Patsopoulos NA, Tatsioni A, Ioannidis JP: Claims of sex differences: an empirical assessment in genetic associations. JAMA. 2007, 298: 880-893. 10.1001/jama.298.8.880CrossRefPubMed
43.
Raby BA, Lazarus R, Silverman EK, Lake S, Lange C, Wjst M, Weiss ST: Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am J Respir Crit Care Med. 2004, 170: 1057-1065. 10.1164/rccm.200404-447OCCrossRefPubMed
44.
Karjalainen J, Nieminen MM, Aromaa A, Klaukka T, Hurme M: The IL-1beta genotype carries asthma susceptibility only in men. J Allergy Clin Immunol. 2002, 109: 514-516. 10.1067/mai.2002.121948CrossRefPubMed
45.
Guilbert TW, Morgan WJ, Zeiger RS, Bacharier LB, Boehmer SJ, Krawiec M, Larsen G, Lemanske RF, Liu A, Mauger DT: Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol. 2004, 114: 1282-1287. 10.1016/j.jaci.2004.09.020CrossRefPubMed
46.
Uekert SJ, Akan G, Evans MD, Li Z, Roberg K, Tisler C, Dasilva D, Anderson E, Gangnon R, Allen DB: Sex-related differences in immune development and the expression of atopy in early childhood. J Allergy Clin Immunol. 2006, 118: 1375-1381. 10.1016/j.jaci.2006.09.008CrossRefPubMed
47.
Barrenas F, Andersson B, Cardell LO, Langston M, Mobini R, Perkins A, Soini J, Stahl A, Benson M: Gender differences in inflammatory proteins and pathways in seasonal allergic rhinitis. Cytokine. 2008, 42: 325-329. 10.1016/j.cyto.2008.03.004CrossRefPubMed
48.
Raby BA, Soto-Quiros ME, Avila L, Lake SL, Murphy A, Liang C, Fournier E, Spesny M, Sylvia JS, Verner A: Sex-specific linkage to total serum immunoglobulin E in families of children with asthma in Costa Rica. Hum Mol Genet. 2007, 16: 243-253. 10.1093/hmg/ddl447CrossRefPubMed
49.
Conde L, Vaquerizas JM, Dopazo H, Arbiza L, Reumers J, Rousseau F, Schymkowitz J, Dopazo J: PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes. Nucleic Acids Res. 2006, 34: W621-625. 10.1093/nar/gkl071PubMedCentralCrossRefPubMed
50.
Shamim Z, Muller K, Svejgaard A, Poulsen LK, Bodtger U, Ryder LP: Association between genetic polymorphisms in the human interleukin-7 receptor alpha-chain and inhalation allergy. Int J Immunogenet. 2007, 34: 149-151. 10.1111/j.1744-313X.2007.00657.xCrossRefPubMed
51.
Hersh CP, Raby BA, Soto-Quiros ME, Murphy AJ, Avila L, Lasky-Su J, Sylvia JS, Klanderman BJ, Lange C, Weiss ST, Celedon JC: Comprehensive testing of positionally cloned asthma genes in two populations. Am J Respir Crit Care Med. 2007, 176: 849-857. 10.1164/rccm.200704-592OCPubMedCentralCrossRefPubMed
52.
Hunninghake GM, Soto-Quiros ME, Avila L, Su J, Murphy A, Demeo DL, Ly NP, Liang C, Sylvia JS, Klanderman BJ: Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood. J Allergy Clin Immunol. 2007, 120: 84-90. 10.1016/j.jaci.2007.04.032CrossRefPubMed
Metadata
Title
Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma
Authors
Supinda Bunyavanich
Erik Melen
Jemma B Wilk
Mark Granada
Manuel E Soto-Quiros
Lydiana Avila
Jessica Lasky-Su
Gary M Hunninghake
Magnus Wickman
Göran Pershagen
George T O'Connor
Scott T Weiss
Juan C Celedόn
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Clinical and Molecular Allergy / Issue 1/2011
Electronic ISSN: 1476-7961
DOI
https://doi.org/10.1186/1476-7961-9-1

Other articles of this Issue 1/2011

Clinical and Molecular Allergy 1/2011 Go to the issue

Research

Exhaled nitric oxide and urinary EPX levels in infants: a pilot study

Research

Anti-allergic and anti-inflammatory effects of butanol extract from Arctium Lappa L

Review

Case report of a young child with disseminated histoplasmosis and review of hyper immunoglobulin e syndrome (HIES)

Review

Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies

Research

Early gene expression changes with rush immunotherapy

Review

The clinical implications of adult-onset henoch-schonelin purpura