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Fungal Illness: Dr. Marinkovich - The Role of IgE and non-IgE

VII. The role of IgE and non-IgE

Allergists have accepted the role that fungal spores can play in eliciting allergy symptoms in susceptible individuals. This is akin to the effects of other airborne organic particles such as pollen, animal dander and insect dust The illness affects only individuals programmed genetically to make large quantities of specific IgE antibodies on exposure to relatively small amounts of allergen. This is type I immunopathology as defined by Gell and Coomb (Gell et al., 1964) and involves the release of pre-formed histamine and other biologically active cytokines from sensitized mast cells and basophils. Symptoms include watery nasal discharge, sneezing paroxysms, itching of the naso-oro-pharyngeal mucosa and tearing eyes, and can be significantly disabling. Symptoms disappear quickly upon cessation of exposure, leaving little, or no, residual effects.

It has been suggested that perhaps five percent of the population may be affected in this way by fungi, although those numbers will vary in different climates (e.g., more in Florida than New Mexico). The great majority of patients presenting with symptoms of fungal illness do not show IgE antibody to the fungus (Fink, 1984). This may be the result of isotype switching from IgE to IgG production as stimulation of the immune system increases. When this happens far more elaborate and damaging immune responses can be generated by the body following exposure to large amount of fungal particles, especially when the exposure is chronic.

These illnesses were originally described in association with various occupational exposures in unprotected workers such as farmer’s lung, bagassosis in sugar cane workers, and many others. More recently such conditions have been identified and studied in office workers whose workplace is contaminated by fungi, especially in buildings with closed ventilation systems (Fink, 1984), in individuals exposed to swamp coolers (Marinkovich et al., 1975) or contaminated air conditioners in the home (Bavaszak et al., 1970), and in many other school, home and workplace exposures, generally as case reports involving a few patients per report (Cakmak et al., 2002) (Hodgeson et al., 1998) (Dales et al., 1991). These symptoms can occur in all individuals with normal immunity because they are ultimately manifestations of a robust immune response to a heavy unrelenting airborne fungal load with consequential overload of clearing mechanisms or macrophages, and the activation of inflammatory processes.

Although the general immune response to a heavy fungal antigen exposure may consist of all the immunoglobulin isotopes (IgA, IgM, IgG, IgD and IgE) plus sensitized lymphocytes or T-cells, specific IgG is the most efficient single marker of generalized immune responses. Specific IgG antibody levels to fungi are not diagnostic when taken alone. However, antibody levels to fungi are directly proportional to levels of exposure in any individual, and generally high exposure levels result in high antibody titers. These antibody levels drop when the patient’s exposure to the offending fungi ends. When elevated, they are helpful in arriving at the presumptive diagnosis and repeat measurements at four to six month intervals help verify compliance with the fungal avoidance program and helps monitor the success of therapy.

A. Immune Complexes

The presence of antibody in the serum is not pathologic in itself. All the immunoglobulins normally present in the tissues, with possible rare exceptions, are antibodies and they contribute to the immune state. It is only when antigen(s) combines with antibody(ies) that immune complexes are formed and a potentially pathologic state is initiated. Immune complexes are not stable since the union is one of complimentary surface configurational attraction between two or more molecules produced by Van der Wall forces. The complexes can easily be disrupted as the conditions in solution change. Changes in temperative, relative numbers of reacting molecules, their nature, the epitope specificity of the reacting antibodies, etc., can all effect changes in the size, shape, surface charges, solubility, of the complex. These factors are the ones that determine the inflammatory potential of the complexes formed and whether the complexes will tend to be deposited in kidneys, joints, blood vessel walls, skin, lungs, etc. (Cochrane et al., 1973). Because of the inherent instability of immune complexes in tissue and serum, they are difficult to study. Interest in understanding immune complexes was very high in the 1950’s and 1960’s and quickly dissolved away when IgE was discovered (Ishizaka et al., 1966) and the attention of the immunological research teams was attracted to the newly defined antibody responsible for classical allergy symptoms, Type I of Gell and Coombs.

There are sound scientific reasons why specific IgG antibodies to fungi are not always diagnostic. Some individuals with high antibody levels to fungi remain symptom free during re-exposure. Such individuals may be less likely to produce the toxic immune complexes required to induce symptoms by virtue of the fungal antigen epitopes to which they respond. They may respond to minor epitopes that allow measurement of the antibody, but which do not engage in the formation of toxic immune complexes. Other individuals may have a vast scavenger system, which can rapidly take up and extinguish all immune complexes generated before symptoms can ensue. Other individuals may satisfy the high exposure and the appropriate symptom requirements and have relatively low total specific antibody levels to fungi. They may be poor antibody responders with an even lower capacity to deal with immune complexes. The observation that they can still experience flu-like symptoms following fungal exposure demonstrates that a relatively low antibody level can still produce significant, disabling symptoms.

Mold toxins can be powerful immune suppressors. It is sobering to remember there would be no organ transplant program without the availability of fungal toxins (e.g., cyclosporin). It is possible and even likely that the fungal exposure of some patients will include exposure to immune suppressive mycotoxins. Another cause for low antibody levels in a symptomatic patient could be iatrogenic. Many patients develop arthritic symptoms and present themselves to rheumatologists who may choose to use an immuno-suppressive drug such as methotrexate to treat the arthritis. Such a drug will certainly depress the immune response, relieve the severity of arthritic symptoms while masking what could be the real trigger for the arthritis.

Quotes

"The ERMI mold test as well as your helpful articles and Toxic Talk Tuesday programs have helped us avoid a terrible mistake in purchasing a new home."

– Angela

"In my moldy home if I left the wet clothes in the washer they would get musty very quickly and I'd have to re-wash... Sometimes I'd run a load, go to work, and they'd be musty when I returned that evening."

– Anonymous

"Both of my sons went downhill quickly and coughed for months... They both lost their ability to read, had profound vision disturbances, and had phenomenal gastric issues."

– Lee

"We were having a lot of health problems and had been to the doctor countless times... we had large circles of slimy greenish-black mold on the bathroom ceiling, where it had caved in a few months before."

– C.

"I knew it was mold, but doctors kept telling me I had anxiety. I was sitting in my office and could not remember who I was talking to, or what we were talking about."

– Brenda

"I've been living in a mold-infested home for 13 months... I was going CRAZY! Finally figured it out... Just a few days of recovering in a mold-free home and I feel AMAZING!!!"

– Lauren

"Our family has been out of our home for 9 months due to mold... I am so scared and weak from all of this. We have lost friends; family members don't understand."

– Anonymous

"We had some water leaks in our home... we never thought we needed to clean out and remove the floor, the ceiling, or the drywall... my two small children and I have remained constantly sick for years in this home."

– Mia

"I was skeptical at first that these (natural cleaning) products would work, but they work better than the stuff I buy at the store! We will soon be moving to the personal care products as well!"

– Jennifer

"My symptoms persisted and eventually turned into lethargy and depression. At the age of 26, I required a nap every evening after work."

– Jennifer

"...at age 35 or 36 I started to become allergic to everything, and I got asthma at age 36... I went to doctor after doctor after doctor and was desperate for help, but nobody could help me."

– Mia

"My daughter has had many blood samples taken to test for everything imaginable and her doctor just seems puzzled. Everything comes back normal."

– Anonymous

"We all suffered from headaches, hormonal body temperature fluctuations, brain fog, fatigue, difficulty breathing, thrush, rashes, and yeast infections... we vacated our home two weeks ago."

– Anonymous

"I had been struggling with headaches, head fog, breathing difficulties (unable to get a full breath), constant scalp tingling, migraines, nausea, feeling spacey/detached, and severe itchy skin."

– Anonymous

"My daughter started having digestive problems... heart palpitations... coughing episodes... muscle/joint pain... asthma/allergies... Her doctor finally advised me to check for mold in our home."

– Anonymous

"I'm new at this, but today I cleaned my bathroom with baking soda and vinegar. It's much better not having those strong chemical smells afterwards."

– Anonymous

"The entire time we lived in our (mold-infested) house the kitchen sponge would get musty smelling within 3-4 days. It was so strange. I had to buy a pack of sponges nearly every week."

– Anonymous

"I have been sick for almost 6 months now and doctors were not able to figure out why. I finally put it all together after going away for vacation for a week and suddenly my symptoms were going away."

– Anonymous

"I started finding myself sitting on the floor in rooms of my house and not remembering how I got there, what I was doing before, or how long I had been there."

– Brenda

Dedication