Indoor Molds

Are There Biomarkers for Human Exposure to Indoor Molds?

Researchers have not yet found reliable biomarkers for human exposure to indoor molds. Biomarkers do exist for the presence of some mycotoxins produced by the ingestion of moldy foods, such as aflatoxin, but those biomarkers do not necessarily apply when inhalation is the exposure route. Instead, current research on biomarkers focuses around serum antibodies to specific mold antigens. IBT Laboratory recently developed an isotype-specific ELISA method to measure IgE, IgG, and IgA levels to Stachybotrys chartarum antigens.

Using antigens as biomarkers poses many problems. Each fungal species can produce many antigens, and those antigens may even cross-react between species. For example, the fungal species Alternaria alternata and Aspergillus fumigatus produce the allergens Alt a1 and Asp f1, respectively. Both of those allergens can produce elevated IgE and IgG antibody levels, and this condition can be used as a diagnostic tool for mold allergies or hypersensitivity. However, the immunological effects are the same for both mold species. Similarly, S. chartarum antigens have been shown to react with both Aspergillus and Alternaria. Finally, while some researchers have used IgG levels as an indication of Stachybotrys exposure, that antibody has been unpredictable and cross-reactive as well.

In summary, reliable biomarkers for human mold exposure are still in the future. As interest in mold toxicity increases, the search for fungal biomarkers may also increase.

Molecular Action of Indoor Molds and Mycotoxins

Stachybotrys molds produce several kinds of mycotoxins, most notably those from the trichothecene and spirolactone families. Of the two, trichothecenes are the most well-studied. Trichothecenes are a family of macrocyclic compounds, encompassing toxins like satratoxins G and H. The numerous deleterious effects of satratoxins on the human body can be broadly categorized into two areas: protein synthesis inhibition and immunosuppression. Again, as with most areas of mold research, the immunosuppressive effects of satratoxins are better understood than the protein synthesis inhibition. Satratoxins can destroy granulocytic precursor cells in bone marrow, leading to white blood cell depletion. They can suppress the blastogenesis of B and T lymphocytes. The presence of satratoxins can decrease the numbers of IgM, IgG, and IgA antibodies present in the body, and they can cause impaired macrophage activity. However, these cellular effects are not yet well understood.

Recent research on Stachybotrys chartarum suggests that exposure to stachylysin, a protein produced by the mold, might be the cause of hemorrhaging in people exposed to the mold. The researchers demonstrated in earthworms that exposure to this protein caused hemoglobin to leak out of the worms’ vascular system. While this topic needs further study, the researchers suggest that a similar mechanism might also be used by other fungal species to produce similar health effects.

Stachybotrys spore, from http://www.apsnet.org/online/feature/stachybotrys/

The molecular actions of Aspergillus molds, particularly A. fumigatus, have been better studied than the action of Stachybotrys toxins. In particular, Slight, et al (1996) have researched the molecular action of the mold upon entering the alveolus of the lung. Upon entering the lungs, A. fumigatus spores first impair the action of macrophages, the immune system’s nonspecific line of defense against foreign material in the body. The spores appear to release a toxin, as of yet unidentified, that halts the assembly and activation of the NADPH complex within the macrophage cell. This inhibits the action of the enzyme oxidase, which in turn halts the macrophage’s ability to produce superoxide anion—the “oxidative burst.” Without this energy, the macrophage cannot engulf the spore through phagocytosis, which constitutes the primary role of macrophages.

Although the identity of this toxin has not yet been determined, the researchers identified several of its most important characteristics. The toxin is probably not a protein, unless it is a very small peptide, and it has carbohydrate characteristics. The mold spore quickly releases the toxin upon entering the alveolus; most of the toxin’s action happens within two minutes of the spore’s introduction into the lung. Finally, and importantly, the toxin does not kill macrophages but instead only impairs their action while the spore is present. If the spore (and toxin) are removed, the macrophage will regain complete ability to perform normal immune functions. Through follow-up studies on this toxin, researchers continue to learn more about it. For example, they have determined that the molecular weight of the toxin is 10kD. Most importantly, the researchers believe this toxin is distinct from other known Aspergillus toxins, and learning more about it can lead to a better understanding of the negative health effects of this mold species.

The A. fumigatus toxin “gliotoxin” is important in long-term exposure to the mold. Gliotoxin allows fungal hyphae to grow in human tissues after the spores have successfully invaded the tissue. Much like the toxin previously discussed, gliotoxin affects the immune capabilities of the host. Gliotoxin halts the phagocytosis actions of macrophages and impairs induction of cytotoxic and alloreactive T-cells. However, gliotoxin also manipulates the normal attachment of epithelial cells and fibroblasts, helping the mold hyphae to grow.

Aspergillus hyphae in lung, from http://www.som.tulane.edu/classware/pathology/medical_pathology/New_for_98/PulmonaryPath/WithText/Pulm-9.html

3-D reconstruction of Aspergillus fumigatus, from http://www.fgsc.net/asperg.html

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Sources

Brieland, Joan K., et al. (2001). Cytokin Networking in Lungs of Immunocompetent Mice in Response to Inhaled Aspergillus fumigatus. Infection and Immunity 2001; 69(3): 1554-1560.

California Department of Health Services (April 1998). Health Effects of Toxin-Producing Indoor Molds in California. Available at: http://www.dhs.cahwnet.gov/ehib/ehib2/topics/toxin_producing.html

California Department of Health Services, Environmental Health Investigations Branch (December 2000). Misinterpretation of Stachybotrys Serology. Available at: http://www.dhs.cahwnet.gov/ehib/ehib2/topics/Serologyf2.htm

Chavez, Hector, et al. (2000). A 4-week old infant with idiopathic pulmonary hemorrhage. Pediatric Emergency Care 2000; 16(1): 42-44.

Etzel, Ruth A. (2002). Mycotoxins. JAMA: The Journal of the American Medical Association 2002; 287(4): 425-427.

Indoor Air Solutions. Stachybotrys chartarum: How do you make the environmental and clinical diagnosis? Available at: http://www.stachybotrys.com/stachy(2).htm

Kilpelainen (2001). Home dampness, current allergic diseases, and respiratory infection among young adults. Thorax 2001; 56(6): 462-467.

Mitchell, Colin G., et al. (1997). Diffusible component from the spore surface of the fungus Aspergillus fumigatus which inhibits the macrophage oxidative burst is distinct from gliotoxin and other hyphal toxins. Thorax 1997; 52: 796-801.

Mycotoxins. Available at: http://mycoherbicide.net/HEALTH/MYCOTOXINS/index.htm

Nelson, Berlin D. (2001). Stachybotrys chartarum: The Toxic Indoor Mold. Available at: http://www.apsnet.org/online/feature/stachybotrys/

Slight, Joan, et al. (1996). Inhibition of the alveolar macrophage oxidative burst by a diffusible component from the surface of the spores of the fungus Aspergillus fumigatus. Thorax 1996; 51(4): 389-396.

Vesper, Stephen J. and Mary Jo Vesper (2002). Stachylysin May Be a Cause of Hemorrhaging in Humans Exposed to Stachybotrys chartarum. Infection and Immunity 2002; 70(4): 2065-2069.

For more information:

http://www.mold-help.org/aspergillus.htm

http://www.moldupdate.com