Genetic Polymorphisms Affecting IDO1 or IDO2 Activity Differently Associate With Aspergillosis in Humans

Aspergillus is the causative agent of human diseases ranging from asthma to invasive infection. Genetic and environmental factors are crucial in regulating the interaction between the host and Aspergillus. The role played by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the first and rate-limiting step of tryptophan catabolism along the kynurenine pathway, is increasingly being recognized, but whether and how genetic variation of IDO1 influences the risk of aspergillosis in susceptible patients is incompletely understood. In addition, whether the closely related protein IDO2 plays a similar role remains unexplored. In the present study, we performed genetic association studies in two different cohorts of susceptible patients [cystic fibrosis (CF) patients and recipients of hematopoietic stem cell transplantation (HSCT)], and identified IDO1 polymorphisms that associate with the risk of infection in both cohorts. By using human bronchial epithelial cells and PBMC from CF and HSCT patients, respectively, we could show that the IDO1 polymorphisms appeared to down-modulate IDO1 expression and function in response to IFN or Aspergillus conidia, and to associate with an increased inflammatory response. In contrast, IDO2 polymorphisms, including variants known to profoundly affect protein expression and function, were differently associated with the risk of aspergillosis in the two cohorts of patients as no association was found in CF patients as opposed to rec...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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CONCLUSION: The use of multiple recombinant antigens may improve the diagnostic accuracy in CF complicated with ABPA or AB. Asp f1 reactivity may relate to the presence of actively growing Aspergillus spp., which might be a useful marker for guiding antifungal therapy in ABPA. PMID: 31090534 [PubMed - as supplied by publisher]
Source: Journal of Medical Microbiology - Category: Microbiology Authors: Tags: J Med Microbiol Source Type: research
Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. This disorder is most commonly seen in patients with poorly controlled asthma and cystic fibrosis. It is rarely reported in chronic granulomatous disease patients; however, there are no cases reported with hematopoietic stem cell transplantation in the English literature. Herein, we report a patient with chronic granulomatous disease who had hematopoietic stem cell transplantation and subsequently developed allergic bronchopulmonary aspergillosis.
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research
In conclusion, a non-negligible proportion of patients with nonspecific alterations of screening tests at baseline may develop Aspergillus-associated syndromes during follow-up. Future studies are needed to confirm our observations.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory infections Source Type: research
Kana Ram Jat, Pankaj C Vaidya, Joseph L Mathew, Sunil Jondhale, Meenu SinghLung India 2018 35(6):499-507 Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease caused by Aspergillus induced hypersensitivity. It usually occurs in immunocompetent but susceptible patients with bronchial asthma and cystic fibrosis. If ABPA goes undiagnosed and untreated, it may progress to bronchiectasis and/or pulmonary fibrosis with significant morbidity and mortality. ABPA is a well-recognized entity in adults; however, there is lack of literature in children. The aim of the present review is to summarize pathophysiology, di...
Source: Lung India - Category: Respiratory Medicine Authors: Source Type: research
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Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Glucocorticoids are the most widely used agents in the treatment of allergic bronchopulmonary aspergillosis (ABPA), a disorder characterised by immunologic reactions mounted against Aspergillus fumigatus colonising the airways of patients with asthma and cystic fibrosis [1, 2]. Unfortunately, the use of glucocorticoids is associated with several adverse reactions [3]. A novel treatment strategy in ABPA would be the use of antifungal triazoles as monotherapy. Recently, we have shown that itraconazole was effective as monotherapy in acute-stage ABPA [4]. Whether voriconazole monotherapy is also efficacious in acute-stage ABPA remains unknown.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Original Articles: Research letters Source Type: research
Authors: Sehgal IS, Dhooria S, Behera D, Agarwal R Abstract Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder that results from immune responses mounted against antigens of Aspergillus fumigatus, resulting in non-specific respiratory symptoms and structural lung damage. Classically defined in individuals suffering from bronchial asthma and cystic fibrosis, ABPA has recently been described in other lung diseases including COPD, pulmonary tuberculosis, idiopathic bronchiectasis and others. Herein, we report the first case of ABPA complicating Swyer-James-Macleod's syndrome that was successfully t...
Source: European Annals of Allergy and Clinical Immunology - Category: Allergy & Immunology Tags: Eur Ann Allergy Clin Immunol Source Type: research
CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function. PMID: 29551015 [PubMed - as supplied by publisher]
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
Allergy to thermotolerant filamentous fungi, particularly Aspergillus fumigatus, is closely associated with fixed airflow obstruction, bronchiectasis, and other radiologically defined abnormalities, such as mucus plugging.1 However, not all asthma patients who are immunoglobulin E (IgE) sensitized to A fumigatus develop these complications. To identify markers of poor outcomes in fungal allergy with asthma (and cystic fibrosis), the term allergic bronchopulmonary aspergillosis (ABPA) was coined.
Source: Annals of Allergy, Asthma and Immunology - Category: Allergy & Immunology Authors: Source Type: research
Allergy to thermotolerant filamentous fungi, particularly Aspergillus fumigatus, is closely associated with fixed airflow obstruction, bronchiectasis, and other radiologically defined abnormalities, such as mucus plugging.1 However, not all asthma patients who are immunoglobulin E (IgE) sensitized to A fumigatus develop these complications. To identify markers of poor outcomes in fungal allergy with asthma (and cystic fibrosis), the term allergic bronchopulmonary aspergillosis (ABPA) was coined.
Source: Annals of Allergy, Asthma and Immunology - Category: Allergy & Immunology Authors: Tags: Letter Source Type: research
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