Chapter 5
Immune Deficiency, Food Allergies, and Yeast Suppression of the
Immune System in Autism
By Dr. William Shaw


 Overview of the Immune System

The critically important job of fighting off infections falls to our immune system. As you might expect, the immune system is complex because the human body must defend itself against 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:

  • B-cells that produce antibodies or immunoglobulins.
  • T-cells (so named because they are derived from the organ called the thymus) are the cells involved in what is called cellular immunity. The functions of the T-cells are to kill foreign tissue or tissues infected and to produce lymphokines, which are large proteins that regulate other cells of the immune system and to help enhance the immune response.
  • The complement system is a group of proteins involved as a nonspecific helper to the immune system.
  • The phagocytic cells include cells called macrophages and neutrophils that engulf bacteria and yeast and digest them.

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 organisms like yeast in the intestinal tract. 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., 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 child with autism’s medical history. In our society, frequent infections lead 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 allow 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.  

  • IgM is usually the first antibody produced by the immune system when a new germ is encountered and it is the body’s early defense system. The presence of high amounts of specific IgM antibodies indicates a recent infection. Thus, high levels of IgM antibodies against Candida would indicate a recent Candida infection of the bloodstream. IgM antibodies diminish a few months after infection.
  • IgG antibodies are produced by the B-lymphocyte cells when a germ attacks in a subsequent invasion. These antibodies may also be involved in causing food allergies.
  • IgE is the antibody most widely known for its involvement in all types of allergies and may also be involved in protecting the body from parasites. Elevated IgE in blood is associated with a history of excessive allergies.
  • IgA is the antibody that is involved with protection of the lining of the nasal passages and intestinal lining from germs. Secretory IgA or sIgA is a special form of the IgA antibody that is secreted to protect the mucosa, which is the lining of the intestinal tract. Secretory IgA is apparently secreted by the gall bladder and then trickles down the bile ducts into the small intestine. Some children with autism have very low or even completely absent levels of IgA (1,2); in such cases there is probably also a deficiency of a secretory IgA since secretory IgA is derived from IgA.
  • IgD is an antibody that is usually present in very small amounts in the bloodstream and is probably involved as a receptor antibody on certain of the white blood cells and may help to regulate antibody production.

One of the conditions that lead 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). Deficiencies of any of the total antibodies indicate 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. An immune deficiency panel that tests for all of these types of antibody deficiencies is available from:

The Great Plains Laboratory Phone: 913 341-8949
11813 W. 77th St. Fax: 913 341-6207
Lenexa, KS 66214  www.greatplainslaboratory.com
E-mail: GPL4U@aol.com  


 Cellular Immunity

The T-cells 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 natural killer (NK) cells 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 of CD4 cells, a T-cell subtype, in children with autism may be another cause of increased colonization with Candida albicans. As mentioned in the chapter on the digestive tract, a deficiency of dipeptidyl peptidase IV may be one of the significant causes of immune abnormalities in autism.


TYPES OF IMMUNE DEFICIENCY THAT OCCUR IN AUTISM

 Myeloperoxidase Deficiency

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 can detect an absence of peroxidase in the neutrophils and monocytes. Certain children with autism should be tested for this disorder, but because the disorder is quite rare, most physicians are not aware of this test.  It is important to be assertive and make sure 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 leukemias (21).

One particular child with autism whose parents consulted with me had severe external manifestations of yeast from a very early age. This 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. Myeloperoxidase deficiency can be tested at the Mayo Clinic Laboratories in Rochester, MN. The phone number is (507)266-5700.  Most myeloperoxidase tests are done for cancer so that you need to include a note indicating that you are interested in genetic myeloperoxidase deficiency as the cause of immunodeficiency.


 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 children with autism with this SCID disorder.)


 Selective IgA Deficiency 

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. Drugs 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 is somewhere between 100 and 200 times higher in the autism population compared to the normal Caucasian population.

IgA replacement therapy cannot be used currently because the short half-life of IgA would make it an extremely expensive therapy1. IgG therapy can be used with patients with low IgA values. If the IgA values are so low that they cannot even be detected, giving IgG therapy would be too risky. It is possible that the immunodeficient person’s body would produce antibodies against IgA, causing potentially fatal anaphylactic shock.


 IgG Subclass 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 C4b 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 allow 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).

Table 1
Types of immune abnormalities in Dr. Gupta’s study of 20 children with autism disorder

Immune 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 is greater than 20
because some children had more than one immune abnormality


 Gliotoxins and Other Immunotoxins Produced by Yeast and Fungi 

Another cause of the recurrent infections associated with yeast overgrowth is 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 (baking yeast) (35). Other compounds produced by yeast also have a significant immunosuppressant effect on the immune system (36-39). The fact that Saccharomyces cerevisiae 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 Byproducts of 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.  Even though there may be an average intake of this vitamin, it is subjected to an increased rate of elimination, resulting in low blood and tissue levels (41). It is likely 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 keep the rats from dying. This animal study indicates that humans, when 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 Wheat and Yeast Connection  

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 would the body produce 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 its own 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 main reason that untreated strep throat is regarded as a serious medical condition, is to prevent this potential autoimmune reaction from occurring.

Vojdani has found that individuals with Candida infections often produce antibodies against Candida that also react against various tissues of the human body including brain, kidney, pancreas, spleen, thymus, and liver (46). Furthermore, these same anti-yeast antibodies also reacted against wheat protein that 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 that 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 injected with the DPT vaccine. 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 these autoantibodies that are causing harm to the body’s own tissues and I believe that existing technology could be adapted for this purpose. As a matter of fact, the success that Gupta’s has had in treating autism with gamma globulin could be related to these autoantibodies being deactivated (20).


THERAPIES

 Gamma Globulin Therapy 

Dr. Gupta has used intravenous immunoglobulin (IVIG) successfully to treat a small number of children with autism (20). IVIG therapy is also called gamma globulin therapy. This product of human plasma has been used to treat immunodeficiency since 1952. Gamma globulin is purified from human blood components and then treated to remove harmful germs such as the HIV virus. Varying degrees of improvement after this therapy reported by Gupta included improved eye contact, calmer and improved social behavior, reduced echolalia, and improved speech in terms of better articulation and improved vocabulary. Speech improvement took the longest time to improve. Several patients regressed when the infusions stopped and then improved again when they were restarted. One child had a nearly complete reversal of the autism after about a year of therapy.
What is the mechanism of this improvement? No one knows for sure. I suspect that the immune system has a better ability to fight yeast and that the reduction of yeast byproducts allows the brain and the body to function better. It may have the effect of suppressing the production of antibodies against myelin, the covering of the nerve fibers in the brain. Elevated levels of this antibody have been reported in this illness. It may be that a specific component of the gamma globulin is responsible for the effects.
Intravenous IgG is usually given once a month due to the 28-day half-life of IgG. After administration of IgG, a child with low IgG values may have values in the normal range. An intravenous infusion takes about 2 hours. A sedative may be given the child to keep the child from being frightened during the procedure.
There are occasional mild and self-limiting reactions to IVIG including fever, muscle aches and pains, headache, nausea and vomiting, dizziness, and tachycardia that occur in less than 5% of all cases. The gamma globulin is derived from human blood so there is also a risk that unknown viruses might be present in the gamma globulin. The gamma globulin is checked for any known viruses such as HIV and hepatitis.   Rarely, there are severe allergic reactions (less than 0.1%). This is a very expensive therapy that may cost as much as $1500-$2500 per month.


 Insurance Coverage for Immune Therapies 

Because immunological therapy for the treatment of autism is considered experimental, most insurance companies and HMO’s will not cover these (substantial) medical expenses.  Since virtually every company will cover expenses due to immune deficiencies, it is essential that the physician document the fact that the child has a significant immune deficiency. Because some insurance companies may not even cover the laboratory tests for the diagnosis of immunodeficiency, the wisest course is to contact a clinical immunologist.

Clinical immunologists are physicians, often associated with a large medical center or medical school, who are working part-time in the treatment of patients and part-time in research activities. These physicians may be of assistance in getting insurance coverage for therapies that are based on an immune deficiency diagnosis—such therapies might not be covered with an autism or PDD diagnosis.

When medical plans and HMOs are reluctant to even provide testing, it may be necessary to begin a letter writing campaign that includes scientific books (such as this one) and articles (referenced herein). If educating them is not persuasive enough, it is sometimes necessary to send letters from an attorney to show that you are very serious about pursuing testing and treatment. You may even want to consider contacting the news media about your dilemma.


 Cimetidine

Cimetidine (Tagamet) is a drug that is primarily used to treat ulcers and is now available as an over the counter (nonprescription) drug. In a review article on candidiasis, Dupont (51) states that this drug is relatively safe and well-tolerated and recommends that this drug be used more frequently to treat patients who have Candidiasis but do not respond adequately to antifungal drugs. Cimetidine has been used at a dose of 30 mg/kg body weight/day to stimulate in the immune system in patients with chronic mucocutaneous Candidiasis (52, 53).  This drug stimulates the white blood cells to kill the Candida. Cimetidine may reduce the rate of metabolism of many other drugs such as the antifungals, antidepressants and antiseizure medications that are absorbed into the bloodstream. Combining zinc supplementation with cimetidine has proven to be very successful in the treatment of recurrent infections in patients with immune deficiency (Int J Clin Lab Research 27:79-80, 1997). Check with your physician and pharmacist before using this drug about an appropriate pediatric dose and any drug interactions that might be associated with the use of this drug.


 Transfer Factor Therapy 

Transfer factors are molecules that may contain both protein and nucleic acids (53) produced by the white blood cells. These molecules can transfer immunity from a healthy donor to a recipient who has impaired immune function. Dr. Masi found that severe Candidiasis could be effectively treated by Candida-specific transfer factor (54).  The results of recent studies show that transfer factor can be given orally, which was surprising since many proteins are destroyed by digestive enzymes when taken orally (55).  Dr. Hugh Fudenberg, a clinical immunologist from the Neuroimmuno-Therapeutics Foundation, found that 21 of 22 children with autism treated with transfer factor from parental cells responded favorably to transfer factor therapy. Ten improved enough to be mainstreamed into regular school classrooms. (26). Dr. Fudenberg believes that either a live virus from one of the vaccines or an adverse reaction between the mother’s antibodies and the vaccine are responsible for impairing the immune system. Transfer factor from bovine colostrum is also available as a food supplement from the 4Life Company. This transfer factor is nonspecific but reports from parents have indicated significant improvements in their children with autism after use. This product is quite expensive ($400 per month).


 Bovine Colostrums 

Colostrum from cows has been used to treat a wide range of diseases including a variety of microbial (bacterial) overgrowths of the gastro-intestinal tract. A major problem with these products is that they contain an appreciable quantity of casein and ninety percent of children with autism are sensitive to casein.  Two casein-free colostrums products that are available on the market is Prime Colostrum from Alt Med available at New Beginnings Nutritionals (www.nbnus.com) and Colostrum Gold from Kirkman.  It is important to remember that some children with autism may be allergic to other milk proteins in addition to casein.  Consequently, children should be given a very small dose at first to determine if there may be an allergic reaction.  If allergic reactions occur, the colostrums should be discontinued immediately.  This product is pasteurized in the same way as milk and should be considered safe from bacteria.  It has been reported that after a relatively short treatment period with casein-free colostrums, some have seen decrease in autistic symptoms and reduced frequency of infections. 


 Pentoxifylline

Pentoxifylline is a drug that is a purine derivative and is an inhibitor of an enzyme called phosphodiesterase. Purines are one of the components of DNA, which is the genetic material for most living creatures. Pentoxifylline was given to a child with autism in Japan to treat suspected brain damage from an accident (56, 57). After this treatment, the boy showed marked improvement of his autistic symptoms. When 23 children with autism were treated with pentoxifylline (150-600 mg/day), the drug was reported to be remarkably effective in 10 of the children with some of the group no longer considered to be autistic. The drug was also very effective in treating seizures. Side effects included nausea, vomiting, low blood pressure, and headache. Since the primary use of this drug is to improve blood circulation, you may find it difficult for a physician to prescribe it to treat autism.


 IL-2 

Interleukin-2 (IL-2) is a protein called a cytokine that stimulates the proliferation and activation of T-cells, B-cells, granular lymphocytes, and macrophages. When T-helper cells are stimulated by antigens from the Candida, white blood cells called T-helper cells produce IL-2 and activate other resting T-cells. IL-2 also stimulates natural killer cells to produce gamma interferon, granulocyte macrophage stimulating factor and other factors that help to fight Candida. Gupta’s work shows that natural killer cells are deficient in children with autism. Although IL-2 is toxic at high doses, low doses of IL-2 are relatively safe. The use of low doses for several weeks would result in selective expansion of natural killer cells that will kill yeast (51). IL-2 is available as a pharmaceutical agent prepared using recombinant DNA. Most family doctors or pediatricians will probably be reluctant to use this product but a clinical immunologist might be willing to discuss the possible use of low dose IL-2 therapy.


 Allergic Phenomena, Food Sensitivity, and Altered Behavior  

A number of reports and books have documented the fact that allergies to foods, molds, and other allergens as well as the direct toxic effects of certain foods can markedly alter behavior.  When the foods and allergens are removed or enzyme-potentiated desensitization (EPD) treatment is pursued, normal behavior can restored (58-71). Doris Rapp M.D. has written several books including Is This Your Child? (58)in which she documents behavioral disorders in children caused by allergic reactions. She also has several videotapes available that dramatically demonstrate bizarre behavior after the introduction of an extract of an allergenic substance. In the book Solving the Puzzle of Your Hard-To-Raise Child by William Crook M.D. (71), many details are given on how to identify and eliminate food allergies and sensitivities. A physician named Dr. Jaeckle, trained as both a psychiatrist and allergist, has recorded individuals on videotape suffering severe psychotic reactions following exposure to mold (72).  Dr. Jaekle concludes that many cases of schizophrenia may have a significant yeast involvement. The Feingold Association, started by the late allergist Ben Feingold M.D., can provide a list of foods that commonly cause hyperactivity, which is a common problem in autism and PDD.


 Tests of Allergies 

There are numerous allergy tests that are available including those that introduce the allergenic substance into the skin (prick test) as well as many other tests that are done on blood. Many laboratories perform the blood tests for IgE and IgG antibodies against specific allergens. These tests should not be confused with tests of total IgG and total IgE that are done to assess a possible immune deficiency. It is possible for an individual to be deficient in total IgG and yet still have high levels of IgG against a specific food.


 IgG and IgE Allergy Tests available from:

The Great Plains Laboratory Phone: 913 341-8949
11813 W. 77th St. Fax: 913 341-6207
Lenexa, KS 66214  www.greatplainslaboratory.com
E-mail: GPL4U@aol.com  


 Immunotherapy with Enzyme-Potentiated Desensitization (EPD)

In autism and PDD, allergies to foods, molds, pollen and other materials may lead to behavioral disturbances in addition to the usual allergic phenomena such as sneezing, asthma, and skin rashes. EPD is a method of immunotherapy developed by Dr. Leonard McEwen (73-77). The method involves desensitization with a combination of very low dose mixed allergens with the enzyme, beta-glucuronidase. The beta-glucuronidase increases the immunizing effects of the allergens and acts directly on T-suppressor cells, apparently inducing a longer lasting desensitization than does any type of previously known immunotherapy. This therapy involves receiving injections every 2 to 3 months at first, and then decreasing over time. The frequency of injections varies with the condition being treated and the patient response, but once maintenance is reached, average patients seem to require treatment 2 to 3 times yearly. Furthermore, McEwen’s experience has been that at least 50% of patients can discontinue EPD between the 8th and 20th injection. Patients have remained in remission without immunotherapy for over 20 years. EPD also appears useful in the treatment of a large variety of conditions not previously considered responsive to immunotherapy of any kind (77).
Numerous parents of children with autism and other behavioral disorders (see chapter by Pamela Scott) have reported beneficial results with this therapy. They also report that their children often don’t do as well when the effects of the EPD begin to wear off just before the next series of EPD injections. As with every therapy, some children respond much more dramatically than others. Unfortunately, the U.S. Food and Drug Administration now limits this therapy to compassionate use only.


 Homeopathy

Homeopathy is a technique employed by both physicians and non-physicians called homeopaths and its theoretical basis is unknown.  This technique involves the preparation of dilutions with the allergy causing substances which a person takes orally to achieve desensitization in a way that is not completely understood. It appears that a small amount of a harmful substance is able to mobilize the body’s own defenses against the substance.  Although not generally approved of by mainstream medicine in this country, many alternative medicine physicians use this technique in their medical practices. This technique is recognized as valid by the World Health Organization and is part of mainstream medicine in France. When trying any new therapy, the best approach is to talk to the physician and with other’s who have experienced the particular therapy and find out how helpful the medical practitioner was. One physician, who employs homeopathy, reported that homeopathic dilutions of arabinose, the sugar derived from Candida, favorably improved behavior in children with autism but that the response only lasted a few days. For the treatment of ear infections (otitis media), homeopathic treatment also appears to be more effective than antibiotic therapy (78).


 Treatment for Allergic Symptoms of Wheat and Dairy Products

In addition to EPD, other methods that have been used for the treatment of food allergies are provocation/neutralization (P/N), and NAET. Laboratory testing such as urinary peptides and IgG antibodies to gluten and casein as well as behavioral response should be used to document the degree of effectiveness of these other non-dietary therapies. Some children seem to lose their sensitivity to these foods after extensive dietary restriction, a phenomenon common in food allergies. Many people may become sensitive to these foods again once these foods are re-introduced, especially if they are ingested on a frequent basis.


 NAET

Nambudripad’s allergy elimination technique or NAET was developed by a nurse/chiropractor; Devi Nambudripad, Ph.D. Practitioners of this technique include physicians, chiropractors, and nurses. Allergies are detected by a technique called applied kinesiology (also called muscle testing) in which the person holds a vial of a substance (to which they may be allergic) and the practitioner assesses their muscle weakness. The validity of this technique, which is difficult to understand because there is no direct physical contact between the allergic substance and the patient, has been documented with conventional blood tests for IgG and IgE food allergies (30). After determination of which foods are problematic, the practitioner treats the allergic reaction by the application of acupressure to a “meridian” or “energy field” of the body that is associated with a specific gastrointestinal function in Eastern medicine (31). Another interpretation is that NAET treatment stimulates the autonomic nervous system that regulates the gastrointestinal tract in such a way that the food allergens are more effectively processed by the digestive and immune systems. Usually the sensitivity to a particular food can be eliminated in a single treatment session but occasionally several treatments are necessary. One of the NAET practitioners (a chiropractor) successfully treated her child with autism who had an extreme gluten sensitivity with this technique. Prior to treatment, gluten caused extremely abnormal behaviors and severe head banging. After treatment, the child was able to eat wheat with no significant behavioral effects. A child with attention deficit hyperactivity (ADHD) was found to have an extremely abnormal brain electroencephalogram or EEG (a tracing of brain electrical activity), but after NAET treatment of food allergies, the EEG was completely normal.

Concerns have been raised that the NAET treatment may clear up allergic responses to wheat and dairy but not the abnormal peptides from wheat and dairy. This is a legitimate concern. I would recommend NAET treatment and/or digestive enzymes to parents who gave up on the gluten and/or casein free diet because their child has become malnourished or ill. Measurement of urine peptides and food allergies in blood samples should be done to confirm the effectiveness of this therapy since it is still unproven. NAET practitioners can be located on the Internet at www.naet.com. It is advisable to obtain recommendations before choosing a practitioner.  Success with this technique varies with the experience of the practitioner.

NAET therapy may cause significant side-effects during and after the clearing process. One parent who used NAET to clear food allergies from her highly allergic child with autism found that it took three treatments to clear her child’s food allergy to sugar. The day after being treated for sugar, her child broke out in hives over his entire body. NAET practitioners consider such reactions as a normal part of the clearing process. Following this severe reaction, the child was no longer sensitive to sugar. When the same child was being treated for wheat, the vial containing wheat caused a welt to develop on the child’s leg where it was touching. The same mother reports that extremely abnormal behavior occurred shortly after the NAET treatments including tantrums, lethargy, and extreme self-stimulatory behaviors and continued for nearly 24 hours. Blood allergy tests done before and after revealed a marked reduction in food allergies after NAET treatments. NAET treatment has also been used to reverse vaccine reactions. No scientific documentation of the success of this therapy for the treatment of vaccine reactions has been reported.

I have used this treatment for my own child who has attention deficit and impulsive behaviors. He had allergies tested by blood and skin prick methods to milk, cheeses, wheat, barley, yeast, peanut, tomato, corn, cats, and pollen. The allergies measured by muscle testing corresponded very closely to the conventional allergy tests. His milk allergy was extremely high by both muscle testing and by the blood allergy tests. He also had high levels of casomorphin and gliadorphin in his urine. His milk allergy could not be eliminated by the standard NAET treatment. The therapist then tested the various digestive organs by palpation with applied kinesiology and found that the bile duct was “sluggish.” An electrode was then applied to the area of the abdomen near the bile duct and a small electrical current was applied for about 45 minutes after which the milk allergy finally “cleared”. Unfortunately NAET therapy appears to only temporarily clear some food allergies, for example, after only a few weeks of being “cleared” of wheat, the wheat sensitivity was again detected using applied kinesiology.  My son realized that he felt much better on the diet and decided to continue on the gluten and casein free diet. Other parents and physicians have also reported to me that NAET was ineffective for wheat and dairy allergies for long-term treatment.

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1 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.


References

  1. Warren R. et al. Immunoglobulin A deficiency in a subset of autistic subjects. J. Autism Develop Dis. 27:187-192,1997.
  2. Warren R. Immune abnormalities in patients with autism.  J. Autism Develop Dis. 16, 189-197, 1986.
  3. Warren R et al Possible association of the extended MHC haplotvpe B44-SC30-DR4 with autism.  Immunogenetics 36: 203-207, 1992.
  4. Warren R et al. Association with decreased plasma levels of the complement C4B protein.  Neuropsychobiology 39: 53-57, 1995.
  5. Singh, V, Warren, RP, Odell, JD, and Cole, P. Changes in soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-I in the serum of children with autism.  Clin. Immunol. Immunopath. 61: 448-455, 1991.
  6. Yonk LJ, Warren RP, Burger RA, Cole P, Odell JD, Warren WL, White E, Singh VK: D4+ per T cell depression in autism.  Immunol Lett 25: 341-346, 1990.
  7. Abramason RK, Self S, Genco P, Smith N, Pendleton A, Valentine J, Wright HH, Cuccaro M, Powell D: The relationship between lymphocyte cell surface markers and serotonin in autistic probands (abstract).  Am J Hum Genet 47(3):A45, 1990.
  8. Wood Frei B, Dennv D, Gaffney GR, O'DonneU T: Lymphocyte subsets and the interleukin-2 system in children with autism (abstract).  Sci Proc Annu Meet Am Acad Child Adolesc Psychiatry 7: 53, 1991.
  9. Plioplys AV, Greaves A, Kazemi K, Silverman Lymphocyte function in autism and Rett syndrome.  Neuropsychobiology 7: 12-16, 1994.
  10. Stubbs EG, Crawford ML, Burger DR, Vanderbark AA: Depressed lymphocyte responsiveness in children with autism.  J Autism Child Schizophr 7:49-55, 1977.
  11. Warren RP, Margaretten NC, Pace NC, Foster A: Immune abnormalities in patients with autism.  J Autism Dev Disord 16:189-197, 1986.
  12. Singh VK, Fudenberg HH, Emerson D, Coleman M: Immunodiagnosis and immunotherapy in children with autism.  Ann NY Acad Sci 540:602-604, 1988.
  13. Ferrari P et al. Immune status in infantile autism: Correlation between the immune status, autistic symptoms and levels of serotonin.  Encephale 14: 339-344, 1988.
  14. Warren RP, Foster A, Margaretten NC: Reduced natural killer cell activity in autism. J Am Acad Child Psychol 26: 333-335, 1987.
  15. Warren PP, Singh VK, Cole P, Odell JD, Pingree CB, Warren WL, White E: Increased frequency of the null allele at the complement C4B locus in autism.  Clin Exp Immunol 83: 438-440, 1991.
  16. Warren R et al. DR-positive T cells in autism: association with decreased plasma levels of the complement C4B protein. Biological Psychiatry 31: 53-57, 1995.
  17. Weizman A, Weizman R, Szekely GA, Wijsenbeek H, Livini E: Abnormal immune response to brain tissue antigen in the syndrome of autism. Am J Psychiatry 139:1462-1465, 1982.
  18. Singh VK, Warren RP, Odell JD, Warren WL, Cole P: Antibodies to myelin basic protein in children with autistic behavior.  Brain Behav Immunity 7: 97-103, 1993.
  19. Plioplys AV, Greaves A, Kazemi K, Silverman Immunoglobulin reactivity in autism and Rett's syndrome.  Dev Brain Dysfunct 7: 12-16, 1994.
  20. Gupta S., Aggarwal and Heads C.  Dysregulated immune system in children with autism.  Beneficial effects of intravenous immune globulin on autistic characteristics. Autism Develop Dis 26:439-452, 1996.
  21. Forehand J, Nauseef W, and Johnston R. Inherited disorders of phagocyte killing. In The Metabolic Basis of Inherited Disease. Sixth Edition. Volume II. Edited by C. Scriver et al. Pgs 2779-2801,1989, McGraw Hill, NY 
  22. Wolf B and Heard G. Disorders of biotin metabolism. In “The Metabolic Basis of Inherited Disease. Volume II. Sixth edition. C. Scriver et al, eds. McGraw Hill, NY,1989, pgs 2093-2103.
  23. Butler J and Cooper M. Antibody deficiency diseases. In The Metabolic Basis of Inherited Disease. Sixth Edition. Volume II. Edited by C. Scriver et al. Pgs 2683-2696,1989, McGraw Hill, NY 
  24. Blaese M. Genetic immunodeficiency syndromes with defects in both T- and B-lymphocyte functions. The Metabolic Basis of Inherited Disease. Sixth Edition. Volume II. Edited by C. Scriver et al. Pgs 2697-2709,1989, McGraw Hill, NY 
  25. Rudduck C, Beckman L, Franzen G, Jacobsson L, Lindstrom L: Complement factor C4 in schizophrenia.  Hum Hered 35:223-226, 1985.
  26. Fudenberg H. Dialyzable lymphocyte extract in infantile onset autism: a pilot study. Biotherapy 9:144, 1996.
  27. Shah D and Larsen B. Identity of a Candida albicans toxin and its production in vaginal secretions. Med Sci Res 20:353-355, 1992.
  28. Shah D and Larsen B. Clinical isolates of yeast produce a gliotoxin-like substance. Mycopathologia 116:203-208, 1991.
  29. Mullbacher A et al. Identification of an agent in cultures of Aspergillus fumigatus displaying anti-phagocytic and immunomodulating activity in vitro. J Gen Microbiol 131:1251-1258, 1985.
  30. Kobayashi M. Gliotoxin treatment selectively spares M-CSF- plus IL-3-responsive multipotent haemopoietic progenitor cells in bone marrow. Eur J of Haematol 46:205-211, 1991.
  31. Sutton P et al. Evidence that gliotoxin enhances lymphocyte activation and induces apoptosis by effects on cyclic AMP levels. Biochem Pharmacol 50:2009-2014, 1995.
  32. Waring P et al. Gliotoxin inactivates alcohol dehydrogenase by either covalent modification or free radical damage by redox cycling. Biochem Pharmacol 49:1195-1201, 1995.
  33. Sprince H et al. Protective action of ascorbic acid and sulfur compounds against acetaldehyde toxicity: implications in alcoholism and smoking. Agents and Actions 5:164-173, 1975.
  34. Podzorski R et al. Pathogenesis of candidiasis. Immunosuppression by cell wall mannan metabolites. Arch Surgery 124: 1290-1294, 1989.
  35. Witkin, S. Defective immune responses in patients with recurrent candidiasis. Infections in Medicine. May / June pg 129-132, 1985.
  36. Iwata K and Ichita K. Cellular immunity in experimental fungal infections in mice. Mykosen Supplement 1:72-81, 1978.
  37. Fischer A, Ballet J, and Griscelli C. Specific inhibition of in vitro Candida-induced lymphocyte proliferation by polysaccharide antigens present in the serum of patients with chronic mucocutaneous candidiasis. J Clin Invest. 62: 1005-1013, 1978.
  38. Carrow E and Domer J. Immunoregulation in experimental murine Candidiasis: specific suppression induced by Candida albicans cell wall glycoprotein. Infection and Immunity 49:172-181, 1985.
  39. Truss O. Metabolic abnormalities in patients with chronic candidiasis: the acetaldehyde hypothesis. J Orthomolecular Psychiatry 13:66-93, 1984.
  40. Lumeng L. The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal-5-phosphate metabolism. J Clin Invest 62:286-293, 1978.
  41. Blum K and Payne J. Alcohol and the addictive brain. The Free Press. NY, NY, pgs 99-216, 1991.           
  42. Tsuboi K et al. Acetaldehyde-dependent changes in hemoglobin and oxygen affinity of human erythrocytes. Hemoglobin 5: 241-250,1981.
  43. Tuma D et al. The interaction of acetaldehyde with tubulin. Ann NY Acad Sci 492:277-286, 1987.
  44. Oldstone M. Molecular mimicry: Immunologic cross reactivity between dissimilar proteins (microbial and self) that share common epitopes can lead to autoimmunity. Cell 50: 819-820, 1987. 
  45. Vojdani A et al. Immunological cross reactivity between Candida albicans and human tissue. J Clin Lab Immunol 48: 1-15, 1996.
  46. Camonis J et al. Characterization, cloning, and sequence analysis of the CD 1986.
  47. Worrall S et al Relationship between alcohol intake and immunoglobulin A immunoreactivity with acetaldehyde-modified bovine serum albumin. Alcohol Clin Exp Res 20: 836-40, 1996.
  48. Pietrzak E et al. Antibodies made against a formaldehyde-protein adduct cross react with an acetaldehyde-protein adduct. Implications for the origin of antibodies in human serum which recognize acetaldehyde-protein adducts. Alcohol 30:373-8, 1995.
  49. Corey L and Petersdorf R. Prevention of Infection: Immunization and antimicrobial prophylaxis. In: Principles of Internal Medicine. Tenth edition. R Petersdorf et al, editors. McGraw Hill, New York, pgs 908-917, 1982.
  50. Dupont P. Candida albicans, the opportunist, a cellular and molecular perspective. J Amer Podiatr ,Med  Assoc 85:104-115,1995.
  51. Gill F and Portnoy J. An unusual combination of immunologic abnormalities in a patient with chronic mucocutaneous candidiasis. Annals of Allergy 63:147-148, 1989.
  52. Jorizzo J. Cimetidine as an immunomodulator: chronic mucocutaneous candidiasis as a model. Ann Intern Med 92: 192-195, 1980.
  53. Fudenberg H and Wilson G. Dialyzable transfer factor: clinical uses and studies on purification of the activity. In Clinical Immunochemistry. The American Association of Clinical Chemistry Press, Washington, DC pgs 228-250, 1978.
  54. Masi M et al. Transfer factor in chronic mucocutaneous candidiasis. Biotherapy 9: 97-103, 1996.
  55. Kirkpatrick C. Activities and characteristics of transfer factor. Biotherapy 9: 13-16, 1996.
  56. Gupta S., Rimland B. and Shilling P. (1995).  Pentoxifylline: A review and a rationale for its possible use in the treatment of autism.  J. Child Neurol 11:501-504, 1996.
  57.   Shimoide M. (1981) Effect of pentoxifylline (Trental) on infantile autism.  Clin.  Exp. Med. 58: 285-288.
  58.   Rapp D. Is This Your Child? 1991.
  59. Eggar, J., Stolla, A., McEwen, L.M. Controlled trial of hyposensitization in children with food-induced hyperkinetic syndrome. Lancet 339:1150-3, 1992.
  60. Rowe K. S., Synthetic food coloring and hyperactivity: A double-blind crossover study. Aust.  Paediatr.  J. 24: l43-47, 1988.
  61. Rowe K, S., Rose K. J. Synthetic food coloring and behavior: A dose response effect in a double-blind, placebo-controlled, repeated-measures study Journal of Pediatrics 12: 691-698, 1994.
  62. Mayron L. Allergy, learning, and behavior problems. Journal of Learning Disabilities 12: 41-51, 1979.
  63. Rapp D.  Does Diet Affect Hyperactivity? J. of Learning Disabilities, 11: 56-62, 1978.
  64. Kaplan, B. J., McNicol J., Conte, R., Moghadam, H. K. Dietary Replacement in Preschool Aged Hyperactive Boys. 83: 7-17, 1989.
  65. Hunter J. 0. Food allergy-or enterometabolic disorder The Lancet 338: 495-6, 1991.
  66. Egger J., Carter C. M., Wilson J., Turner M. W., Soothill J. F. Is migraine food allergy?  A double-blind controlled trial of oligoantigenic diet treatment. Lancet ii: 865-69, 1983.
  67. Egger J., Carter C.M., Graham P.J., Gumby D., Soothill J.F. Controlled trial of oligoantigenic treatment in the hyperkinetic syndrome, Lancet i: 540-45,1985.
  68. Crook W. G., Can What a Child Eats Make Him Dull, Stupid, or Hyperactive? Journal of Learning Disabilities, 13: 53-58, 1980.
  69. Clarke, T. The relation of allergy to character problems in children. A survey. Annals of Allergy March-April, 1950, pp. 175-87.
  70. Boris M., Mandel F. Food and additives are common causes of the attention deficit hyperactive disorder in children. Annals of Allergy 72: 462-68,1994.
  71. Crook W and Steven L. Solving the Puzzle of Your Hard-To-Raise Child. Professional Books.Jackson, TN, 1987.
  72. Yeast-related mental disturbances. Psychiatric symptoms elicited through biological (physical) mechanisms. An interview with Richard G Jaeckle M.D.. Mastering Food Allergies. 10(1): 1-4, 1995.
  73. McEwen, L.M., Starr, M.S. Enzyme potentiated hyposensitization I, The effect of pre-treatment with beta-glucuronidase, hyaluronidase, and antigen on anaphylactic sensitivity of guinea pigs and mice. Int Arch Allerg42: 152-8, 1972.
  74. McEwen, L.M. Enzyme potentiated hyposensitization II, Effect of glucose, glucosamine, N-acetylamino-sugars and gelatin on the ability of beta-glucuronidase to block the anamnestic response to antigen in mice. Ann Allerg 31:79-83, 1973.
  75. McEwen, L.M., Nicholoson, M., Kitchen, I. and White, S. Enzyme potentiated hyposensitization III, Control by sugars and diols of the immunological effect of beta-glucuronidase in mice and patients with hay fever. Ann Allerg 31:543-9, 1973.
  76. McEwen, L.M., Nicholoson, M., Kitchen, I., O'Gorman, J., White, S. Enzyme potentiated hyposensitization IV, Effect of protamine on the immunological behavior of beta-glucuronidase in mice and patients with hay fever. Ann Allerg 34:290-5, 1975.
  77. McEwen, L.M. Enzyme potentiated hyposensitization V, Five case reports of patients with acute food allergy. Ann Allerg 35:98-103, 1975.
  78. Friese KH et al. Otitis media in children: A comparison of conventional and homeopathic drugs. Head and Neck Otorhinolaryngology 44:462-466, 1996.