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Cytokine profiling of pulmonary aspergillosis
Author(s) -
Sambatakou H.,
Pravica V.,
Hutchinson I. V.,
Denning D. W.
Publication year - 2006
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.2006.00616.x
Subject(s) - allergic bronchopulmonary aspergillosis , aspergillosis , aspergillus fumigatus , genotype , immunology , cytokine , medicine , allele , bronchoalveolar lavage , allele frequency , ccpa , lung , biology , gene , immunoglobulin e , antibody , adenosine receptor , biochemistry , receptor , agonist
Summary Aspergillus fumigatus is ubiquitous and yet causes invasive, chronic and allergic disease of the lung. Chronic cavitary pulmonary aspergillosis (CCPA) is a slowly destructive form of pulmonary aspergillosis, without immunocompromise. We hypothesized that CCPA cytokine gene polymorphisms would differ from patients with allergic bronchopulmonary aspergillosis (ABPA) and uninfected controls. We have profiled functional cytokine gene polymorphisms for interleukin (IL)‐10, IL‐15, transforming growth factors (TGF)‐β1, tumour necrosis factor (TNF)‐α and interferon (IFN)‐γ in patients with CCPA ( n = 24) who were compared with other forms of aspergillosis (mostly ABPA) ( n = 15) and with ethnically matched controls ( n = 65–330). Results are described with reference to the high‐producing genotype in each case. Susceptibility to aspergillosis (all patients compared with normal controls) was associated with higher frequency of the IL‐15 +13689*A allele (OR = 2.37, P = 0.0028) and A/A genotype (χ 2 = 10.31, P < 0.001), with a lower frequency of the TNF‐α−308*A/A genotype (χ 2 = 11.05, P < 0.01). Within the aspergillosis patients, CCPA is associated with lower frequency of the IL‐10 −1082*G allele (OR = 0.38, P = 0.0006) and G/G genotype (χ 2 = 22.45, P < 0.001) and with a lower frequency of the TGF‐β1 +869 *T allele (OR +0.42, P < 0.0029) and T/T genotype (χ 2 = 17.82, P < 0.001) compared with non‐CCPA patients and normal controls. Patients infected with Aspergillus appear to be higher producers of IL‐15, a Th2‐promoting cytokine, and lower producers of TNF‐α, a cytokine central in protective responses. CCPA occurs in patients who are genetically lower producers of both IL‐10 and TGF‐β1. As these cytokines are regulatory and anti‐inflammatory, CCPA may be a consequence of poor inflammatory response control in the lung.