IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level
Abstract
Objective The aim of this study was to determine whether interleukin-1 alpha (IL1alpha), interleukin-1 beta (IL1beta), and IL1 receptor antagonist (IL1Ra) polymorphisms are implicated in invasive pulmonary aspergillosis (IPA) pathogenesis.Materials and methods Subjects comprised 110 hematological patients and 148 healthy controls. Genotypic and allelic frequencies were similar between hematological patients and controls. IPA was diagnosed in 59 of the 110 patients according to consensus criteria published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/IFICG).Results and discussions Individual locus analysis showed that IL1alpha and IL1Ra polymorphisms were not associated with the presence of IPA (p = 0.560 and p = 0.680, respectively). However, a trend towards a higher presence of IL1beta( - ) (511TT) genotype (or IL1beta(-511T) allele) in the IPA group than in the non-IPA patient group (p = 0.092 and p = 0.095, respectively) was found. Haplotype analysis revealed that VNTR2/-889C/-511T haplotype was strongly associated with susceptibility to develop IPA infection (p = 0.020). Haplotype analysis also showed an association between VNTR2/-889C/-511C haplotype and resistance to IPA infection (p = 0.028). Furthermore, patients with IL1Ra VNTR2/2 and IL1beta(-511)T/T genotypes had a higher positive serum galactomannan percentage versus patients with other genotypes. Finally, C-reactive protein (CRP) production was significantly associated with IL1 gene cluster polymorphisms, although CRP values were similar between IPA and non-IPA groups.Conclusion These findings indicate a critical role of IL1 gene cluster polymorphisms in the susceptibility to IPA infection and CRP production.
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Polymorphisms in several cytokines are associated with susceptibility to specific fungal diseases: aspergillosis with IL-1, IL-10, IL-15, and IL-23; candidiasis with IL-4; paracoccidioidomycosis with IL-4; and blastomycosis with IL-6.
“polymorphisms in a number of cytokines have also been found to predispose to fungal disease: aspergillosis (IL-1 [30], IL-10 [31,32], IL-15 [32], and IL-23); candidiasis (IL-4) [33,34]; paracoccidioidomycosis (IL-4) [35]; and blastomycosis (IL-6) [36].”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [30]
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Sainz, J., Salas-Alvarado, I., López-Fernández, E., Olmedo, C., Comino, A., García, F., Blanco, A., Gómez-Lopera, S., Oyonarte, S., Bueno, P., et al. (2010) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201002300205 · Cited by 56 · see citing works
Self-citationRace and ethnicity: Risk factors for fungal infections?
Jenks, J. D., Aneke, C. I., Al-Obaidi, M. M., Egger, M., Garcia, L., Gaines, T., Hoenigl, M., & Thompson, G. R. (2023) · PLOS Pathogens · doi:10.1371/journal.ppat.1011025 · Cited by 55 · see citing works
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Lupiañez, C. B., Canet, L. M., Carvalho, A., Alcazar-Fuoli, L., Springer, J., Lackner, M., Segura-Catena, J., Comino, A., Olmedo, C., Ríos, R., et al. (2016) · Infection and Immunity · doi:10.1128/iai.01359-15 · Cited by 42 · see citing works
Self-citation
- Authors
- Sainz, J., Pérez, E., Gómez-Lopera, S., & Jurado, M.
- Affiliations
- Hospital Universitario Virgen de las Nieves (ES)
- ORCID
- Jurado, M.
- Venue
- Journal of Clinical Immunology
- Published
- 2008-05-17
- Volume
- 28
- Issue
- 5
- Pages
- 473-485
- ISSN
- 0271-9142 (ISSN-L)
- 1573-2592
- OpenAlex
- W2025186579
- Cited by
- 84
- References
- 88
- Citations by year
- 2025: 3 · 2023: 3 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 12 · 2014: 11 · 2013: 5 · 2012: 2
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Servicio Andaluz de Salud
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- invasive pulmonary aspergillosis, interleukin-1 gene cluster, IL-1α, IL-1β, genetic polymorphism, haplotypes, C-reactive protein, hematologic patients, infection susceptibility, galactomannan
- MeSH terms
- Aspergillosis, Aspergillus, C-Reactive Protein, Female, Galactose, Multigene Family, Haplotypes, Humans, Lung Diseases, Fungal, Male, Mannans, Statistics as Topic, Immunocompromised Host, Hematologic Neoplasms, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Receptors, Interleukin-1 Type I, Interleukin-1alpha, Interleukin-1beta, Drug-Related Side Effects and Adverse Reactions
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