| DB ID | MyCo_1817 |
| Title | Th2 and Th9 responses in patients with chronic mucocutaneous candidiasis and hyper-IgE syndrome |
| Year | 2016 |
| PMID | 27474157 |
| Fungal Diseases involved | Chronic mucocutaneous candidiasis |
| Associated Medical Condition | Hyper IgE syndrome (HIES) |
| Genus | Candida |
| Species | albicans |
| Organism | Candida albicans |
| Ethical Statement | All experiments were performed and conducted in accordance to Good Clinical practice, the Declaration of Helsinki, and the approval of the Arnhem-Nijmegen Ethical Committee (nr.2010/104). |
| Site of Infection | None |
| Opportunistic invasive | Opportunistic |
| Sample type | Body fluid |
| Sample source | Blood |
| Host Group | Human |
| Host Common name | Human |
| Host Scientific name | Homo sapiens |
| Biomarker Name | IL-13 |
| Biomarker Full Name | Interleukin-13 |
| Biomarker Type | Diagnostic |
| Biomolecule | Protein |
| Geographical Location | China |
| Cohort | Blood was collected from healthy volunteers or patients by venous blood puncture after informed consent. Healthy volunteers between 20 and 40 years of age with no chronic disease or allergic disease in their history as well as without any medication were asked for blood donation. Four CMC patients with an autosomal dominant mutation in the STAT1 gene donated blood, two of them twice at two different time points. Four patients diagnosed with HIES with an autosomal dominant mutation in the STAT3 gene were asked for blood donations; two of them donated blood twice at different time points. Four patients with atopic dermatitis (AD) recruited from the department of dermatology and diagnosed according to their clinical presentation were included into the study. Peripheral blood mononuclear cells of CMC patients (n=4), HIES patients (n=4), atopic dermatitis patients (n=4) and healthy volunteers (n=13) were stimulated with Candida and Staphylococcus aureus, with and without IL-4. The cytokines IL-5, IL-13, IL-9, IL-17 and TGFβ and regulatory T cells were measured in cell culture supernatants by ELISA or flowcytometry, respectively. |
| Cohort No. | 25 |
| Age Group | 20-41 |
| P Value | p< 0.05 |
| Sensitivity | None |
| Specificity | None |
| Positive Predictive Value | None |
| MIC | None |
| Fold Change | None |
| Pathway | None |
| Disease Introduction Mechanism | Atopic diseases such as asthma or atopic dermatitis are classically driven by an elevated T helper (Th) 2 response, characterized by the cytokines Interleukin (IL) -4, IL-5 and IL-13. These cytokines mediate a type 1 immediate hypersensitivity reaction associated with IgE class switch and eosinophil recruitment that is followed by a late phase allergic reaction caused by infiltrating allergen-specific T cells that lead to persistent allergic symptoms. Next to the Th2 cells, other T helper cell subpopulations have been identified as important players driving pathological atopic reactions. This includes not only an imbalance between Th1 and Th2 cells or between Th2 cells and regulatory T cell, but also disturbed immune responses of the more recently identified Th17 and Th9 cells. IL-17A (hereafter named IL-17), produced by Th17 cells, is an important pro-inflammatory cytokine in the host defence against extracellular pathogens, especially against Candida, but can also drive pathology in allergic airway inflammation, where IL-17 was identified to induce IgEmediated late-phase asthmatic response and granulocyte influx. IL-9, another proinflammatory cytokine derived from Th9 cells after differentiation from a naïve T cell in the presence of IL 4 and transforming growth factor (TGF) β, leads to mast cell activation, eosinophil recruitment and IgE class switch during allergic inflammation. Neutralization of IL-9 in an ovalbumin-induced asthma model was shown to significantly reduce allergic symptoms. Interestingly, next to the distinct Th lineage of Th9 cells, Th17 have also been described to be a source for IL-9. TGFβ and IL-1β were thereby identified as the main inducers of IL-9 and IL-17 co-expressing cells and mainly driving pathology in auto-immune diseases. A Th17 deficient immunological phenotype does not implicitly lead to altered allergic immune responses. The recently identified gain-of-function (GOF) mutation in STAT1 leads to deficient IL-17 production. Patients with STAT1 GOF-mutation display next to recurrent infections and a higher incidence of auto-immune diseases or oesophageal cancer also chronic mucocutaneous candidiasis (CMC), manifesting as fungal infections on skin, nails and mucous membranes, but an atopic constitution is not a feature of the clinical presentation in these patients. In contrast, patients with the autosomal dominant loss-offunction (LOF) STAT3 mutation, also leading to a deficient IL-17 production, present with an atopic phenotype with eczema, eosinophilia and high IgE levels, as well as recurrent staphylococcal skin, pulmonary abscesses accompanied by bronchiectasis and also CMC. In the present study we wanted to elucidate whether the clinical allergic phenotype in HIES correlates with alterations in Th2 and Th9 immune responses, and compare this with patients without allergic symptoms that share many features of HIES including a Th17 deficiency, namely CMC. |
| Technique | ELISA |
| Analysis Method | ELISA Based |
| ELISA kits | ELISA kits (IL-5, IL-13, IL-17, IL-22 and TGFβ: R&D Systems; IL-9: Biolegend) |
| Assay Data | None |
| Validation Techniques used | ELISA, Flowcytometry |
| Up Regulation Down Regulation | Decrease |
| Sequence Data | None |
| External Link | None |
