Interagency Agreement on Immunotoxicology Research
The NIEHS and NIOSH interagency agreement provides support of NTP hazard identification activities aimed at preventing diseases or adverse effects caused by environmental exposure to chemical or physical agents. These cooperative studies continue to improve risk assessment, by measuring what constitutes an adverse health effect on the immune system in humans. The studies, listed in the table below, evaluate unique cohorts of individuals from professions associated with immune-mediated occupational diseases.
To develop species-specific monoclonal antibodies to recombinant fungal biomarker antigens. The utility of these antibodies will be important for the quantification of fungal biomarkers, particularly to those fungi that are being studied by NTP. In this project, Aspergillus terreus was initially used as a model fungal organism for the development of fungal-specific proteins using recombinant technologies. Aspergillus terreus hemolysin was produced by recombinant technology, and a panel of species-specific monoclonal antibodies was also produced. The same recombinant technologies were used to identify and characterize additional candidate fungal allergens. Recombinant Chaetomium globosum enolase (rec-CgEnol) has been cloned, expressed, purified, and confirmed using mass spectrometry. Three rec-CgEnol specific immunoglobulin G1 (IgG1) monoclonal antibodies have been produced and characterized. Several manuscripts have been published that report these findings. The development of a sensitive immunoassay that can be used in the serological detection of this biomarker is anticipated.
To characterize the toxicological and pulmonary immune responses associated with subchronic fungal exposures using a model that replicates human exposure. This model utilizes an acoustical generator system, and nose-only exposure chamber to characterize toxicological endpoints following subchronic dry fungal spore and particle exposures. Following completion of a related study in FY 2014, a secondary aim of this project is to characterize subchronic toxicity and pulmonary immune responses to fungal contaminants nominated to the NTP, including Stachybotrys chartarum both mycotoxin producing and nonproducing chemotypes, Aspergillus versicolor, and Alternaria alternata. In FY 2015, protocols were submitted to NTP for the evaluation of Aspergillus versicolor and a mycotoxin producing chemotype of Stachybotrys chartarum. Alternaria alternata, mixed fungal exposures, and other occupationally relevant fungi identified in concurrent NTP funded diversity studies will be evaluated in future fiscal years. These toxicological studies will provide novel datasets that will be used to characterize the hazards that fungal exposure may represent to human health.
To investigate and characterize the diversity of fungal bioaerosols in the indoor and occupational environments, using large-scale ribosomal RNA sequencing. In collaboration with Assured Bio Labs LLC, Columbia University, and NIOSH in FY 2015, our laboratory has evaluated indoor and occupational environments, using large-scale ribosomal RNA approaches from samples collected in contaminated and noncontaminated environments. In addition, fungal species identified in this analysis will be directly compared to commercially available methods of fungal analysis, including the Environmental Relative Mold Index.
To examine potential roles of exposure to fungal toxins on occupants’ health in water-damaged buildings. We plan to (1) develop a cost-effective and robust method, using an ultra-performance liquid chromatography-tandem mass spectrometry, for simultaneous analysis of multiple fungal toxins in environmental samples; (2) increase accuracy of the method by using isotopically labeled (C13) mycotoxin internal standards to compensate for extraction loss and matrix effects; (3) apply the method to examine stability of mycotoxins in floor dust stored in different temperature conditions for different lengths of time; and (4) quantify fungal toxins in floor dust samples that have been collected from a funded school study in FY 2015 and previous studies of water-damaged buildings. These studies also have other types of exposure data, including fungal biomass, bacterial biomass, and occupants’ health, which can be adjusted for in statistical models to examine the effect of exposure to fungal toxins on occupants’ health.