Detection of mycotoxins in patients with chronic fatigue syndrome.

Over the past 20 years, exposure to mycotoxin producing mold has been recognized as a significant health risk. Scientific literature has demonstrated mycotoxins as possible causes of human disease in water-damaged buildings (WDB). This study was conducted to determine if selected mycotoxins could be identified in human urine from patients suffering from chronic fatigue syndrome (CFS). Patients (n = 112) with a prior diagnosis of CFS were evaluated for mold exposure and the presence of mycotoxins in their urine. Urine was tested for aflatoxins (AT), ochratoxin A (OTA) and macrocyclic trichothecenes (MT) using Enzyme Linked Immunosorbent Assays (ELISA). Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin (one in the equivocal range). Almost 30% of the cases had more than one mycotoxin present. OTA was the most prevalent mycotoxin detected (83%) with MT as the next most common (44%). Exposure histories indicated current and/or past exposure to WDB in over 90% of cases. Environmental testing was performed in the WDB from a subset of these patients. This testing revealed the presence of potentially mycotoxin producing mold species and mycotoxins in the environment of the WDB. Prior testing in a healthy control population with no history of exposure to a WDB or moldy environment (n = 55) by the same laboratory, utilizing the same methods, revealed no positive cases at the limits of detection.

Neural autoantibodies and neurophysiologic abnormalities in patients exposed to molds in water-damaged buildings.

Adverse health effects of fungal bioaerosols on occupants of water-damaged homes and other buildings have been reported. Recently, it has been suggested that mold exposure causes neurological injury. The authors investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling, tremors, and muscle weakness in the extremities). Serum samples were collected and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and mycotoxins were also determined with ELISA, as reported previously. Neurophysiologic evaluations for latency, amplitude, and velocity were performed on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with documented, measured exposure to molds had elevated titers of antibodies (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve conduction studies revealed 4 patient groupings: (1) mixed sensory-motor polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3) sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no neurophysiological abnormalities (n = 20, normal controls). All groups showed significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG) of antibodies to neural antigens when compared with 500 healthy controls. Groups 1 through 3 also exhibited abnormal neurophysiologic findings. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.

Mixed mold mycotoxicosis: immunological changes in humans following exposure in water-damaged buildings.

The study described was part of a larger multicenter investigation of patients with multiple health complaints attributable to confirmed exposure to mixed-molds infestation in water-damaged buildings. The authors present data on symptoms; clinical chemistries; abnormalities in pulmonary function; alterations in T, B, and natural killer (NK) cells; the presence of autoantibodies (i.e., antinuclear autoantibodies [ANA], autoantibodies against smooth muscle [ASM], and autoantibodies against central nervous system [CNS] and peripheral nervous system [PNS] myelins). A total of 209 adults, 42.7 +/- 16 yr of age (mean +/- standard deviation), were examined and tested with (a) self-administered weighted health history and symptom questionnaires; (b) standardized physical examinations; (c) complete blood counts and blood and urine chemistries; (d) urine and fecal cultures; (e) thyroid function tests (T4, free T3); (f) pulmonary function tests (forced vital capacity [FVC], forced expiratory volume in 1 sec [FEV1.0], and forced expiratory flow at 25%, 50%, 75%, and 25-75% of FVC [FEF25, FEF50, FEF75, and FEF2(25-75)]); (g) peripheral lymphocyte phenotypes (T, B, and NK cells) and mitogenesis determinations; and (h) a 13-item autoimmune panel. The molds-exposed patients reported a greater frequency and intensity of symptoms, particularly neurological and inflammatory symptoms, when compared with controls. The percentages of exposed individuals with increased lymphocyte phenotypes were: B cells (CD20+), 75.6%; CD5+CD25+, 68.9%; CD3+CD26+, 91.2%; CD8+HLR-DR+, 62%; and CD8+CD38+, 56.6%; whereas other phenotypes were decreased: CD8+CD11b+, 15.6% and CD3-CD16+CD56+, 38.5%. Mitogenesis to phytohemagglutinin was decreased in 26.2% of the exposed patients, but only 5.9% had decreased response to concanavalin A. Abnormally high levels of ANA, ASM, and CNS myelin (immunoglobulins [Ig]G, IgM, IgA) and PNS myelin (IgG, IgM, IgA) were found; odds ratios for each were significant at 95% confidence intervals, showing an increased risk for autoimmunity. The authors conclude that exposure to mixed molds and their associated mycotoxins in water-damaged buildings leads to multiple health problems involving the CNS and the immune system, in addition to pulmonary effects and allergies. Mold exposure also initiates inflammatory processes. The authors propose the term "mixed mold mycotoxicosis" for the multisystem illness observed in these patients.

Antibodies to molds and satratoxin in individuals exposed in water-damaged buildings.

Immunoglobulin (Ig)A, IgM, and IgG antibodies against Penicillium notatum, Aspergillus niger, Stachybotrys chartarum, and satratoxin H were determined in the blood of 500 healthy blood donor controls, 500 random patients, and 500 patients with known exposure to molds. The patients were referred to the immunological testing laboratory for health reasons other than mold exposure, or for measurement of mold antibody levels. Levels of IgA, IgM, and IgG antibodies against molds were significantly greater in the patients (p < 0.001 for all measurements) than in the controls. However, in mold-exposed patients, levels of these antibodies against satratoxin differed significantly for IgG only (p < 0.001), but not for IgM or IgA. These differences in the levels of mold antibodies among the 3 groups were confirmed by calculation of z score and by Scheffé's significant difference tests. A general linear model was applied in the majority of cases, and 3 different subsets were formed, meaning that the healthy control groups were different from the random patients and from the mold-exposed patients. These findings indicated that mold exposure was more common in patients who were referred for immunological evaluation than it was in healthy blood donors. The detection of antibodies to molds and satratoxin H likely resulted from antigenic stimulation of the immune system and the reaction of serum with specially prepared mold antigens. These antigens, which had high protein content, were developed in this laboratory and used in the enzyme-linked immunosorbent assay (ELISA) procedure. The authors concluded that the antibodies studied are specific to mold antigens and mycotoxins, and therefore could be useful in epidemiological and other studies of humans exposed to molds and mycotoxins.