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Immune deficiency, immunizations, and yeastsuppression of the immune system
by William Shaw Ph.D.
Overview of the immune system.
The critically important job of fighting off infections falls to our immune system. As you might expect, this is a complex system; it must be, because the invasions faced by the human body include diverse infectious agents including bacteria, viruses, fungi, etc.
Recent research by several scientists has shown that children with autism have serious abnormalities in this all-important system. In order to understand these abnormalities, and to show what effect they might have for the child with autism, it is essential to have a basic understanding of the immune system.
The immune system is made up of several different parts.
A large part of the immune system is located in or near the intestinal tract and helps to prevent germs from the intestine from entering into the rest of the body. Defects in the immune system may therefore lead to overgrowth of the intestinal tract with organisms like yeast.
A defect in any of these systems may lead to increased incidence of infection. Defects in all parts of the immune system have been documented in children with autism. Studies done by the late Reed Warren Ph.D. at Utah State University, Sudhir Gupta M.D. Ph.D., a clinical immunologist at the University of California at Irvine Medical School, and others indicate that most children with autism have a substantial immune abnormality of some type (1-20). This probably explains why frequent infections are a common feature of the autistic child's medical history. In our society, frequent infections leads to frequent use of antibiotics. Some parents of children with autism have reported to me over 50 consecutive ear infections in their children. The antibiotics prescribed for ear infections also kill many of the normal organisms in the intestinal tract, and allows abnormal organisms such as yeast and bacteria such as Clostridia to proliferate in the intestinal tract.
Antibodies or immunoglobulins.
The B-lymphocyte cells of the immune system produce antibodies called immunoglobulins. These antibodies are designed to react against specific antigens-foreign molecules introduced into the system by germs of various types. Antibodies react against viruses, yeast, and bacteria and allow them to be killed by the white blood cells. Composed mostly of amino acids, antibodies are proteins that can be divided into five major antibody classes called IgA, IgG, IgM, IgD, and IgE. Each has a unique chemical structure and a specific function. IgG stands for immunoglobulin G or antibody G and so forth.
One of the factors that leads to recurrent otitis media or other recurrent infections is called immunodeficiency, meaning the presence of a weak or deficient immune system. Immunodeficiency can be caused by a deficiency of antibodies such as IgG, IgA, and IgM. Children with autism have a high frequency of abnormalities of these different kinds of antibodies (20). A deficiency of any of the total antibodies indicates a probable immunodeficiency. In addition, the total amount of a particular antibody could be normal but the amount of a specific antibody might be deficient. For example, I suspect that many children with autism and PDD may be deficient in producing antibodies against yeast.
Cellular immunity.
The T-cells (so named because they are derived from the organ called the thymus) are the cells involved in what is called cellular immunity. T-cells kill foreign tissue or tissues infected with virus, and produce lymphokines. Lymphokines are large proteins that regulate other cells of the immune system, and help to enhance the immune response. Some of these proteins are called interleukins (IL). Eighteen different interleukins have been identified. Other proteins produced by the white blood cells include interferon, granulocyte-macrophage colony stimulating factor (GC-CSF), and tumor necrosis factor. Concentrations of IL-12 and interferon gamma are much higher in the blood of children with autism than in normal children, indicating an immune activation, possibly due to adverse vaccine reactions. In addition to T-cells, another type of lymphocyte (a white blood cell type) called a natural killer (NK) cell is also important in the immune system. The data from Warren and Gupta indicates that 38-45% of children with autism have low NK cell numbers as well as significant T-cell abnormalities. The decrease in children with autism of CD4 cells, a T-cell subtype, may be another cause of increased colonization with Candida albicans.
Types of immune deficiency that occur in autism.
Myeloperoxidasedeficiency.
Myeloperoxidase is an enzyme present in the white blood cells (neutrophils) that combines hydrogen peroxide and chloride ions to form hypochlorite ion, the same active ingredient present in household bleach (21). The hypochlorite ion kills yeast just like household bleach does. If this enzyme is deficient, the white blood cells cannot produce sufficient hypochlorite to kill the yeast and the affected person cannot fight off yeast infection satisfactorily.
This disorder can be detected by the use of automated flow cytochemistry instruments that detect an absence of peroxidase in the neutrophils and monocytes, and should be tested in autistic children. Because the disorder is quite rare, most physicians will not be aware of this test; you should be assertive and ensure that the right type of blood test is used. Because these cells look completely normal under the microscope, a routine blood examination is not a satisfactory test for this disorder. Most patients with this disorder have frequent yeast and fungal infections and often have fungal infections of the nails or even systemic yeast infections. Myeloperoxidase deficiency can be genetic or acquired. The genetic type is due to a mutation on chromosome pair 17 or to biotinidase deficiency (21,22). Acquired causes include lead poisoning, folic acid or vitamin B-12 deficiency, severe infection, and leukemia (21).
A child with autism whose parents have consulted me has had severe external manifestations of yeast from a very early age. The child had fungal infection of the skin and nails and had been on antifungal drugs for years. The child was ultimately diagnosed with myeloperoxidase deficiency, and she responded well to intravenous gamma globulin therapy, which is described later in the chapter. Every child with external manifestations of yeast or fungal infections should be tested for possible myeloperoxidase deficiency.
Severe combined immunodeficiency disease (SCID).
Severe combined immunodeficiency disease is a defect in both the T and B-lymphocytes so that both antibody production and cellular immunity are impaired (23,24). This disease can be due to a genetic deficiency on the X chromosome or on one of the other chromosomes. Genetic deficiencies of the enzymes purine nucleoside phosphorylase or adenosine deaminase also cause SCID. Candida infections as well as other infections are common in this disorder. (Although not published in the medical literature, I have had personal communication with parents of autistic children with this SCID disorder.)
Selective IgAdeficiency
This extremely common immunodeficiency occurs in 1 in 600-1000 persons of European ancestry (23). The causes of IgA deficiency are not completely known. There are some cases in which the deficiency runs in families while in other cases it does not. It has been reported in association with abnormalities of chromosome 18, but most individuals with IgA deficiency have no detectable chromosomal abnormalities. Dr.ugs or viral infection may also cause IgA deficiency. Patients with IgA deficiency are usually deficient in both subtypes of IgA, IgA1 and IgA2.
A number of patients with IgA deficiency are also sensitive to gluten. In Gupta's study (20), 20% of the children with autism had a deficiency of IgA and 8% lacked it completely. Reed Warren and his colleagues (2) also found that 20% of individuals with autism had low serum IgA compared with none of the normal controls. Thus, IgA deficiency in autism is somewhere between 100 and 200 times higher in the autism population compared to a normal Caucasian population.
IgA replacement therapy cannot be used currently because the short half-life of IgA would make it an extremely expensive therapy. IgG therapy can be used with patients with low IgA values. If the IgA values are so low that they cannot even be detected, however, giving IgG therapy is too risky. It is possible that the immunodeficient person's body would produce antibodies against IgA, causing potentially fatal anaphylactic shock.
IgGsubclass deficiency.
Sometimes the total IgG in the blood may be normal but the concentration of one or more subtypes of IgG may be low. There are four subtypes of IgG: IgG1, IgG2, IgG3, and IgG4. Antibodies against proteins are mainly of the IgG1 and IgG3 subtypes while antibodies against carbohydrates (sugars) are of the IgG2 subtype (23). In Gupta's study (20), 20% of the children with autism had an IgG subclass deficiency (Table 1). There are hundreds of different kinds of antibodies within each antibody type so that there could be an IgG antibody against rubella, another against smallpox, and another against whooping cough and so on. When all the different types of IgG are measured simultaneously, the total IgG is measured.
Complement deficiency.
The complement system is a complex group of 20 proteins that assist or "complement" the work of the immune system by destroying invading yeast, viruses, and bacteria. The complement system can disintegrate the cell membranes of many species of bacteria, and complement byproducts attract scavenger white blood cells to the site of the bacteria destruction. These scavengers then clean up the dead bacteria debris.
Some of the complement components also coat the bacteria, which allows the bacteria to be more easily digested by the scavenger white blood cells. Reed Warren and his colleagues found that the average concentration of one of the proteins in the complement system termed C4b was significantly lower than normal in individuals with autism (15). Complement C4b deficiency is also increased in schizophrenia (25). Individuals with low amounts of this protein are more susceptible to infection from yeast and bacteria such as Streptococcus pneumoniae and Haemophilus influenza, two of the bacteria most commonly responsible for ear infections (15).
Kinds of immune abnormalities in Dr. Gupta's study of 20 children with autism
|
Disorder |
Number of cases* |
| Common variable immunodeficiency | 2 |
| IgG1 deficiency | 1 |
| IgG2 deficiency | 4 |
| IgG4 deficiency | 2 |
| IgG3 and myeloperoxidase deficiency | 1 |
| Low IgG | 1 |
| Increased IgE | 7 |
| Increased antibodies to myelin basic protein | 6 |
|
Specific antibody deficiency with normal IgG and IgG subclasses |
1 |
|
IgA deficiency |
4 |
*The number of types of immune deficiency are greater than 20 because some children had more than one immune abnormality.
Immunodeficiency testing for IgG, IgG subclasses, IgA, IgM, IgG, and zinc can be performed at The Great Plains Laboratory.
Role of immunizations in causing immune deficiencies.
Gupta found high amounts of antibodies to rubella (German measles) in mothers of children with autism (20). Gupta states that these high amounts of antibodies would be transferred across the placenta and may also persist for a prolonged period in the child. If the infant receives the rubella immunization while antibodies are still present (which is now more likely because of earlier immunization schedules), the antibodies may react with the rubella virus in the vaccine forming immune complexes that "confuse" the immune system (20). Dr. Hugh Fudenberg (26), a clinical immunologist reported that some patients with autism "developed symptoms (of autism) within a week after immunization with the measles, mumps, and rubella (MMR) vaccine." Dr. Fudenberg also found that some of these children also had extremely high fever or seizures within one day of the vaccine. Reed Warren and his colleagues (15) think that children with this immune deficiency "may not be able to clear certain viruses completely or before the viruses affect the central nervous system."
One mother whose child reacted unfavorably after the MMR writes (27): "Nicholas has severe mental impairment after having the MMR injection. He has no speech, no understanding of language at all, no concentration, bizarre behavioral problems, and rarely acknowledges anyone. He has become very strong and aggressive. He is having constant tantrums, screaming and flinging himself to the ground and biting anyone who tries to restrain him. He is very frustrated and agitated most of the time; Our son was once a bright, happy, normal child who could speak and love everyone."
In several cases, electron microscopy has revealed live measles virus in the intestinal lining of children with autism, raising the possibility that the MMR may actually be responsible for some of the gastrointestinal abnormalities common in children with autism. Any child with autism who complains of gastrointestinal pain or who reacted adversely to the MMR should receive an endoscopic examination of the intestinal tract to detect damage to the intestinal lining. Increased mortality in children in developing nations receiving measles vaccine has been reported to occur six to twelve months after immunization probably due to immune suppression (J Inf Dis 173:1320-6,1996; Lancet 348: 1257-8,1996). The vaccine damage fund in the United States that compensates families for harm caused by vaccines does not award compensation for autism caused by vaccination. The legislation establishing the compensation fund should be amended to include vaccine damage causing autism and other severe diseases. The amendment of this legislation should be a top political priority of the Autism Society of America.
Thus, it is possible that a viral infection (derived from a live vaccine) of the intestine has caused certain of the intestinal cells to malfunction in the production of secretin or peptidases needed to prevent the toxic effects of wheat or milk peptides. Based on many similar case reports, parents who already have a child with autism who reacted adversely to an immunization might wish to consider delaying immunizations for subsequent children to two years or later or ask that the vaccines be given separately rather than in the combined form like the MMR. The diseases prevented by these immunizations might also increase the risk of harm to a growing child but this risk is decreased when most other children in the community are immunized.
Gliotoxinsand other immunotoxins produced by yeastand fungi
Another cause of the recurrent infections associated with yeast overgrowth are chemical compounds called gliotoxins. Gliotoxins are immunotoxic, meaning they are toxic to the immune system. They are compounds that are produced by both yeast (28,29) and fungi such as Aspergillus (30). (Gliotoxins have no relationship to the glial cells of the brain and were named after the species of fungus Gliocladium in which they were first discovered.) Most strains of Candida that were isolated from humans have the ability to produce gliotoxins (28). Gliotoxins are important because they selectively fragment the DNA of white blood cells called T-lymphocytes and macrophages so that they are ineffective in fighting off infections (31,32). This is probably why the gliotoxins are so important and why Candida often causes recurrent infections. I suspect that exposure to gliotoxins may be a major cause of the frequent immune deficiencies in autism.
A second toxic effect of gliotoxins is probably due to their action on the sulfhydryl group of proteins, which they inactivate. These sulfhydryl groups are necessary for the functioning of a wide variety of enzymes (33). Supplements of glutathione, N-acetyl cysteine, and lipoic acid might be useful to prevent this toxic action of gliotoxins since they help to regenerate free sulfhydryl groups.
A third way that gliotoxins may be causing their damage is by the generation of compounds called free radicals (33). Free radicals are highly reactive chemicals that can cause many harmful effects to the body such as damaging our genetic material DNA. Many of these harmful reactions can be counteracted by compounds called antioxidants such as vitamin C, vitamin E, lipoic acid, glutathione, or N-acetyl cysteine. Several physicians who treat large numbers of children with autism have indicated to me significant improvement of symptoms in some children with autism after treatment with the nutritional supplements glutathione or N-acetylcysteine. It seems likely that prevention of free-radical damage induced by gliotoxins may be one of the reasons these supplements are effective.
Mannan is another yeast product that comes from both Candida and Saccharomyces cerevisiae(35). Other compounds produced by yeast also have a significant immunosuppressant effect on the immune system (36-39).The fact that Saccharomyces cerevisiae (baking yeast) produces immune suppressants is one of the reasons that I recommend a yeast-free diet in addition to sugar restriction to control a yeast overgrowth of the intestinal tract. Even if the yeast cells are completely killed by baking (and some people think they may survive in the center of baked goods where the temperature may be lower), these immunosuppressant mannan compounds may not be destroyed by heating.
Other toxic byproductsof Candida.
According to Orion Truss M.D., the pioneer in the treatment of yeast-related illnesses, acetaldehyde is one of the most important toxic yeast byproducts (40). Vitamin B-6 is an aldehyde that must react with amino groups on many different enzymes throughout the body in order for them to function. If these amino groups have been used up by reacting with acetaldehyde, then other biochemical reactions mediated by vitamin B-6 cannot take place. The vitamin is subjected to an increased rate of elimination, resulting in low blood and tissue levels of this vitamin even though there may be an average intake of this vitamin (41). I suspect that high doses of vitamin B-6 may overcome the competition with acetaldehyde caused by the yeast and may be one of the main reasons that this vitamin is effective for the treatment of autism. I also suspect that high doses of vitamin B-6 may not be needed if the yeast are controlled; (see chapters on organic acids and vitamin therapy). A controlled study needs to be done to prove this idea.
Acetaldehyde may also react with neurotransmitters such as dopamine and serotonin to form opiate-like compounds called tetrahydroisoquinolines (42), which have been isolated from the urine of alcoholics. This is another way that an intestinal yeast overgrowth may affect brain function. Acetaldehyde also decreases the flexibility of the red blood cells (43) so that they are less able to deliver oxygen to the tissues. In addition, acetaldehyde decreases the ability of the protein tubulin to assemble into microtubules, which may interfere with transfer of essential biochemicals into the dendrites, the fibers that are used for nerve cell communication in the brain (44). In a study on rats given lethal doses of acetaldehyde (34), administration of lipoic acid or N-acetyl cysteine was able to prevent the death of any of the rats. This animal study indicates that humans exposed to this same byproduct due to yeast overgrowth might also benefit from increased intake of these same nutritional products.
Autoimmunity, molecular mimicry, and Candida. The wheatand yeastconnection.
Singh has found that a high percentage of children with autism possess antibodies against their own tissues called autoantibodies (18). One of these autoantibodies is directed against myelin a fatty sheath that insulates the axons of nerve cells like the plastic insulator on electrical wire. Why is the body producing antibodies against its own tissue? Sometimes the body mounts an attack against an invading germ and produces antibodies against it. If one of the germs possesses proteins on its surface that resemble human tissue, then the antibodies may be "fooled" to react against the human tissue. The best known example of this molecular mimicry is rheumatic fever in which antibodies produced against a Streptococcal or "Strep" infection later react against the heart valve tissue (45,46). The autoimmune reaction from untreated Strep throat is the main reason that this condition is treated as a serious medical condition.
Vojdani has found that individuals with Candida infections often produce antibodiesagainst Candida that also react against various tissues of the human bodyincluding brain, kidney, pancreas, spleen, thymus, and liver (46). Furthermore, these same anti-yeast antibodies also reacted against wheat protein which may explain why so many children with autism have high titers of wheat antibodies and are sensitive to wheat. A portion of one of the major wheat proteins called alpha-gliadin is very similar to a portion of one of the yeast proteins that is involved in yeast reproduction (47). Antibodies produced against yeast may be "tricked" into reacting against wheat because of the great similarity of portions of the two different proteins. This protein could be an important link between wheat and yeast sensitivity in autism.
If Orion Truss's acetaldehyde hypothesis is correct, the high reactivity of acetaldehyde may also provide an explanation for the high percentage of children with autoantibodies as well as the severe reactions some children experience after vaccination. Acetaldehyde reacts with virtually any free amino group on both proteins and amino acids. The amino acid lysine is one of the 20 amino acids found in most proteins. It is unusual in that it possesses two amino groups instead of one. This extra amino group on lysine is the target for acetaldehyde when it reacts with proteins. (This amino group is also the site at which arabinose reacts; see chapter on organic acids.)
It has been found that alcoholics who form greater than usual amounts of acetaldehyde possess antibodies against acetaldehyde-altered proteins (48). Furthermore, it has been found antibodies against acetaldehyde-altered proteins may cross react against formaldehyde-altered proteins (49). The toxins from diphtheria and tetanus bacteria are treated with formaldehyde to prepare the DPT vaccine (50). It is possible that if a child possesses antibodies against acetaldehyde-modified proteins due to yeast overgrowth, the vaccine may stimulate a marked increase in the autoimmune reaction, perhaps leading to a severe adverse immune reaction. According to Ellen Bolte of Cure Autism Now, her child's autism began a few days after her child was vaccinated with the DPT injection. He was on antibiotics for ear infection at the time of the immunization and it is possible that a yeast overgrowth may have predisposed him to the adverse immune reaction.
I think that a possible role of human antibodies to Candida in reacting against myelin and other brain structures should be thoroughly investigated. In the future, it may be possible to deactivate or remove auto-antibodies that are causing harm to the body's own tissues. It appears to me that existing technology could be adapted for this purpose. As a matter of fact, Gupta's success in treating autism with gamma globulin might be working by removal of such autoantibodies (20).
A half-life is the length of time required for half of a substance to disappear from the bloodstream. When a medicine or chemical has an extremely short half life, it must be administered very frequently. (Continue to Part II.)
Buy The newest version (2002) of this book online!
Biological Treatments for Autism and PDD Online > Chapter 5: Part I | Part II