Framework ascribing immunodeficiency to fungal susceptibility
| Principles . | Comments . |
|---|---|
| Robust diagnosis of fungal disease | Since the clinical and radiographic features of fungal disease can be nonspecific, employing standardized definitions, such as that of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), is essential to ensure robust mycosis phenotype. This is crucial for establishing a strong association between fungal disease and underlying immunodeficiency |
| Temporality | For genetically mediated immunodeficiencies, the mycosis must have occurred prior to any medical intervention that may, itself, predispose to fungal disease (e.g., immunosuppressants, transplantation, and indwelling catheter). |
| Clinical reproducibility | Repeated clinical observation strengthens the association between an immune defect and fungal susceptibility. In the case of genetically mediated immunodeficiency, a threshold of at least three unrelated cases reporting the association to the gene has been previously proposed (Vinh, 2023, 2024). In the case of ultra-rare IEI, where this threshold may not be feasible, it would be even more imperative that immunobiological validation be pursued. |
| Immunobiological validation | Although this is the most stringent criteria and may not always be feasible, it is optimal that the immunobiological mechanism linking loss of immune function to the specific fungal disease be confirmed in an experimental setting. |
| Principles . | Comments . |
|---|---|
| Robust diagnosis of fungal disease | Since the clinical and radiographic features of fungal disease can be nonspecific, employing standardized definitions, such as that of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), is essential to ensure robust mycosis phenotype. This is crucial for establishing a strong association between fungal disease and underlying immunodeficiency |
| Temporality | For genetically mediated immunodeficiencies, the mycosis must have occurred prior to any medical intervention that may, itself, predispose to fungal disease (e.g., immunosuppressants, transplantation, and indwelling catheter). |
| Clinical reproducibility | Repeated clinical observation strengthens the association between an immune defect and fungal susceptibility. In the case of genetically mediated immunodeficiency, a threshold of at least three unrelated cases reporting the association to the gene has been previously proposed (Vinh, 2023, 2024). In the case of ultra-rare IEI, where this threshold may not be feasible, it would be even more imperative that immunobiological validation be pursued. |
| Immunobiological validation | Although this is the most stringent criteria and may not always be feasible, it is optimal that the immunobiological mechanism linking loss of immune function to the specific fungal disease be confirmed in an experimental setting. |