Introduction
Molds are microscopic fungi ubiquitous in the environment. In immunosuppressed patients, they cause localized or systemic infections. What is less well-known outside allergy clinics is that molds are frequent airborne sensitizers involved in allergic diseases, the most frequent and life-threatening being allergic bronchopulmonary mycosis (ABPM). Most reported cases are attributed to Aspergillus fumigatus (Af), which are referred to as allergic bronchopulmonary aspergillosis (ABPA). ABPA occurs in patients with a history of chronic lung disease, such as cystic fibrosis (CF), asthma, or chronic obstructive pulmonary disease (1). The current hypothesis is that chronic inflammatory bronchial diseases alter the immune responses by triggering a Th2 immune response instead of an efficient immune clearance following contact with molds (2, 3). Despite several diagnostic criteria updates, the main criterion still relies on the evaluation of humoral IgE and IgG responses to Af extracts, with the shortcoming that these cannot discriminate Af sensitization from ABPA (4). The determination of IgE responses to Af individual proteins with proven allergenicity, commonly referred to as “molecular allergens,” improves ABPA diagnostic accuracy (5, 6). Yet, although ABPM was firstly described and most frequently associated with Af, other molds have been documented to trigger allergic pulmonary disease. Their diagnostic criteria are poorly defined and they are infrequently reported in the literature.
The evaluation of the functional cellular responses against allergens is a diagnostic criterion that is currently used in international guidelines (7, 8). Ex vivo basophil activation test (BAT) investigates immediate hypersensitivity events whereas lymphocyte stimulation test (LST) explores delayed hypersensitivity. In both tests, whole blood is incubated with serial concentrations of a suspected allergen, followed by flow cytometric quantification of upregulated activation markers (9, 10). Data are scarce for mold-related allergic diseases (11–13). This study aimed to assess the relevance of functional cellular assays for ABPM diagnosis and review ex vivo basophil and lymphocyte functional cellular tests in ABPM diagnosis.