Genetic Susceptibility to Allergic Bronchopulmonary Aspergillosis in Asthma: a Genetic Association Study

Overview

Journal Allergy Asthma Clin Immunol

Specialty Allergy & Immunology

Date 2016 Oct 7

PMID 27708669

Citations 19

Authors

Nicola L D Overton

David W Denning

Paul Bowyer

Angela Simpson

Affiliations

Soon will be listed here.

Abstract

Background: In patients with asthma, the fungus can cause allergic bronchopulmonary aspergillosis (ABPA). Familial ABPA is reported, and some genetic factors have been associated with the disease, however, these are small studies (n ≤ 38) and do not explain all cases of ABPA.

Methods: We analysed SNPs in 95 ABPA patients, comparing frequencies to 152 atopic asthmatic and 279 healthy controls. Twenty two genes were selected from literature, and 195 tagging SNPs were analysed for genetic association with ABPA using logistic regression corrected for multiple testing. We also analysed monocyte-derived macrophage gene expression before and during co-culture with .

Results: Seventeen ABPA-associated SNPs (ABPA v Atopic asthma) were identified. Three remained significant after correction for multiple testing; IL13 rs20541, IL4R rs3024656, TLR3 rs1879026. We also identified minor differences in macrophage gene expression responses in the ABPA group compared to the control groups.

Conclusions: Multiple SNPs are now associated with ABPA. Some are novel associations. These associations implicate cytokine pathways and receptors in the aberrant response to and susceptibility to ABPA, providing insights into the pathogenesis of ABPA and/or its complications. We hope these results will lead to increased understanding and improved treatment and diagnostics for ABPA.

Citing Articles

Respiratory Outcomes and Aspergillus Serology Following Elexacaftor/Tezacaftor/Ivacaftor Therapy in People with Cystic Fibrosis and a History of Aspergillus fumigatus Infection.

Lanfranchi C, Alicandro G, Cariani L, Orena B, Gramegna A, Rizza C Lung. 2025; 203(1):24.

PMID: 39762638 DOI: 10.1007/s00408-024-00781-4.

Anti-IL-4Ra therapy is superior to other biologic classes in treating allergic bronchopulmonary aspergillosis.

Lamothe P, Pruett C, Smirnova N, Shepherd A, Runnstrom M, Park J J Allergy Clin Immunol Glob. 2024; 4(1):100369.

PMID: 39736892 PMC: 11683235. DOI: 10.1016/j.jacig.2024.100369.

Fungal lung disease.

Jaggi T, Agarwal R, Tiew P, Shah A, Lydon E, Hage C Eur Respir J. 2024; 64(5).

PMID: 39362667 PMC: 11602666. DOI: 10.1183/13993003.00803-2024.

Variants of human DECTIN-1 rs16910526 are linked to differential reactive oxygen species production and susceptibility to tuberculosis.

Cufre M, Pastorini M, Martin I, Failde R, Palmero D, Aleman M J Biomed Sci. 2024; 31(1):77.

PMID: 39103844 PMC: 11302830. DOI: 10.1186/s12929-024-01067-w.

Polymorphisms in Innate and Adaptive Immune Genes in Subjects with Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

Kanaujia R, Arora A, Chakrabarti A, Rudramurthy S, Agarwal R Mycopathologia. 2024; 189(2):23.

PMID: 38407762 DOI: 10.1007/s11046-024-00834-5.

References

Steele C, Rapaka R, Metz A, Pop S, Williams D, Gordon S . The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog. 2005; 1(4):e42. PMC: 1311140. DOI: 10.1371/journal.ppat.0010042. View

Halwig J, Kurup V, Greenberger P, Patterson R . A familial occurrence of allergic bronchopulmonary aspergillosis: a probable environmental source. J Allergy Clin Immunol. 1985; 76(1):55-9. DOI: 10.1016/0091-6749(85)90804-8. View

Denning D, Pleuvry A, Cole D . Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol. 2012; 51(4):361-70. DOI: 10.3109/13693786.2012.738312. View

Chen W, Ericksen M, Levin L, Khurana Hershey G . Functional effect of the R110Q IL13 genetic variant alone and in combination with IL4RA genetic variants. J Allergy Clin Immunol. 2004; 114(3):553-60. DOI: 10.1016/j.jaci.2004.04.044. View

Soubani A, Chandrasekar P . The clinical spectrum of pulmonary aspergillosis. Chest. 2002; 121(6):1988-99. DOI: 10.1378/chest.121.6.1988. View

Denis O, van den Brule S, Heymans J, Havaux X, Rochard C, Huaux F . Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodelling. Immunology. 2007; 122(2):268-78. PMC: 2265999. DOI: 10.1111/j.1365-2567.2007.02636.x. View

Vaid M, Kaur S, Sambatakou H, Madan T, Denning D, Sarma P . Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Clin Chem Lab Med. 2007; 45(2):183-6. DOI: 10.1515/CCLM.2007.033. View

Hohl T, Van Epps H, Rivera A, Morgan L, Chen P, Feldmesser M . Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display. PLoS Pathog. 2005; 1(3):e30. PMC: 1287910. DOI: 10.1371/journal.ppat.0010030. View

Bellocchio S, Moretti S, Perruccio K, Fallarino F, Bozza S, Montagnoli C . TLRs govern neutrophil activity in aspergillosis. J Immunol. 2004; 173(12):7406-15. DOI: 10.4049/jimmunol.173.12.7406. View

10.

Loeffler J, Haddad Z, Bonin M, Romeike N, Mezger M, Schumacher U . Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus. J Med Microbiol. 2008; 58(Pt 1):49-58. DOI: 10.1099/jmm.0.003293-0. View

11.

Sleiman P, Flory J, Imielinski M, Bradfield J, Annaiah K, Willis-Owen S . Variants of DENND1B associated with asthma in children. N Engl J Med. 2009; 362(1):36-44. DOI: 10.1056/NEJMoa0901867. View

12.

Langley S, Goldthorpe S, Craven M, Morris J, Woodcock A, Custovic A . Exposure and sensitization to indoor allergens: association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma. J Allergy Clin Immunol. 2003; 112(2):362-8. DOI: 10.1067/mai.2003.1654. View

13.

Kesh S, Mensah N, Peterlongo P, Jaffe D, Hsu K, van den Brink M . TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann N Y Acad Sci. 2006; 1062:95-103. DOI: 10.1196/annals.1358.012. View

14.

Miyake Y, Kiyohara C, Koyanagi M, Fujimoto T, Shirasawa S, Tanaka K . Case-control study of eczema associated with IL13 genetic polymorphisms in Japanese children. Int Arch Allergy Immunol. 2010; 154(4):328-35. DOI: 10.1159/000321825. View

15.

Agarwal R, Khan A, Aggarwal A, Gupta D . Link between CFTR mutations and ABPA: a systematic review and meta-analysis. Mycoses. 2011; 55(4):357-65. DOI: 10.1111/j.1439-0507.2011.02130.x. View

16.

Cui L, Jia J, Ma C, Li S, Wang Y, Guo X . IL-13 polymorphisms contribute to the risk of asthma: a meta-analysis. Clin Biochem. 2012; 45(4-5):285-8. DOI: 10.1016/j.clinbiochem.2011.12.012. View

17.

Carvalho A, Pasqualotto A, Pitzurra L, Romani L, Denning D, Rodrigues F . Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis. 2008; 197(4):618-21. DOI: 10.1086/526500. View

18.

El-Gedaily A, Schoedon G, Schneemann M, Schaffner A . Constitutive and regulated expression of platelet basic protein in human monocytes. J Leukoc Biol. 2003; 75(3):495-503. DOI: 10.1189/jlb.0603288. View

19.

Katakura T, Miyazaki M, Kobayashi M, Herndon D, Suzuki F . CCL17 and IL-10 as effectors that enable alternatively activated macrophages to inhibit the generation of classically activated macrophages. J Immunol. 2004; 172(3):1407-13. DOI: 10.4049/jimmunol.172.3.1407. View

20.

Murdock B, Shreiner A, McDonald R, Osterholzer J, White E, Toews G . Coevolution of TH1, TH2, and TH17 responses during repeated pulmonary exposure to Aspergillus fumigatus conidia. Infect Immun. 2010; 79(1):125-35. PMC: 3019910. DOI: 10.1128/IAI.00508-10. View