by Aristo Vojdani, PhD
According to the Autoimmune Disease Society, 53 million Americans suffer from some form of autoimmune disease or associated disorder. A 2005 National Institutes of Health (NIH) report1 estimates that 23.5 million Americans suffer from autoimmune disease alone; by now this number may have increased to 30 million. An estimated 10% of the world population experiences some form of autoimmune disease, and another 10% is in the process of developing one of these disorders. Over the past four decades, rates of autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, and lupus have tripled in Western countries. There is a significant need for biomarkers for the early detection of autoimmune disorders, so clinicians will be forewarned and guide their patients in preventive measures.
Predictive Antibodies in Autoimmunity
Researchers have identified more than 80 autoimmune conditions and suspect at least 40 more disorders of having an autoimmune basis. These conditions are chronic and many can be life-threatening.
The predictive function of antibodies. Research was conducted by the author several decades ago under an NIH grant to establish a test for measuring antibodies predictive of type 1 diabetes. We found that children developed antibodies against one or more components of islet cell antigens at least five to ten years before the onset of the disease. From this we learned that detection of tissue-specific antibodies could be used as an early biomarker of autoimmune disease.
Increasing predictive accuracy. A research protocol developed by A. L. Notkins, MD, an NIH immunologist, evaluated patients for diabetes risk by measuring antibodies against insulin, GAD-65 (glutamic acid decarboxylase), and islet cell antigens (protein tyrosine phosphatase).2 He found that measuring antibodies against just one antigen, such as insulin, the probability of predicting the disease was only 12%. When measuring antibodies against two antigens such as GAD-65 and PTP, the predictive accuracy increases to 50%. By measuring antibodies against all three of these antigens, predictive ability approaches 75%. The insight from this study is that the more tissue-specific antibodies we measure and the more antigens we identify, the better we can predict the risk of the disease.
This research provided further evidence of the "early warning" function of antibodies, concluding, "…predictive autoantibodies appear in the blood years before people show symptoms of various disorders. Tests that detected these molecules could warn of the need to take preventive action."2
The potentiating effect of antigens. Several articles published in scientific journals have reported that children with type 1 diabetes develop the disease much faster if put on baby formula containing cow's milk.3,4 While this does not constitute evidence that milk causes type 1 diabetes, the consensus in the literature is that the presence of dairy antigens potentiates the disease. If we remove that antigen from the diet, and immune potentiation does not occur, perhaps the development of autoimmune disease in that child will be delayed or avoided.
Correlation of antibodies and autoimmune reactivity. In patients with celiac disease (CD) or non-celiac gluten sensitivity (NCGS), it has been established that the probability of having one (or several) other autoimmune diseases is 30 times higher than in those who do not have these conditions. The incidence of gluten ataxia, for example, which manifests in disorders such as autism, is increased up to 30-fold in patients with celiac disease.5
In order to implement preventive measures, it is extremely important to identify antibody reactivity before significant tissue damage has occurred. If we detect autoimmunity at an early stage, we can help millions of people reverse the course of this disease.
Cross-Reactivity in Foods
The concept of cross-reactivity enables us to address factors beyond gluten sensitivity with targeted therapies. Cross-reactivity explains how immune sensitization to an antigen such as alpha-gliadin can trigger an immune attack against tissues and organs.
Immune sensitization and cross-reactivity. Gliadin is a prime example of an antigen that cross-reacts with other foods, as well as with human tissue antigens, causing symptoms of celiac disease beyond the gut.6 Food cross-reactivity is a sinister phenomenon that occurs as a result of the similarity in the sequence of amino acids in food proteins and in tissues and organs. Surprisingly, cross-reactivity can occur in a duplicate sequence involving as few as ten or so amino acids out of possibly hundreds.
Limitations of the gluten-free diet. It is widely reported in journal articles that patients with celiac disease frequently have abnormal villous atrophy,7 indicating complete destruction of certain gut tissues.Many clinicians have the impression that removing gluten from the diet will make a significant difference, reversing villous atrophy. However, research has found that when CD patients were put on a gluten-free diet, after six months only 8% of these patients had reversal of villous atrophy. An additional 65% of patients showed 50% improvement. The remaining 27% experienced no improvement in their clinical condition.8
Evaluating food cross-reactivity. We conducted a study to evaluate cross-reactivity between alpha-gliadin and extracts of numerous foods, including grains such as corn, millet, oats, and rice; dairy products; and other foods that are often recommended to patients on a gluten-free diet.9 The author tested this premise using two different sets of highly specific, purified antibodies made against alpha-gliadin 33-mer peptide, the major antigen causing celiac disease. One set of these antibodies consisted of polyclonal antibodies that were affinity purified, indicating that approximately 99% reacted with alpha-gliadin. All other reactive components had been removed to ensure that the antibodies were only reacting to the amino acid sequences of alpha-gliadin. In addition, highly specific monoclonal antibodies prepared against alpha-gliadin were utilized.
We tested the reactions of both the polyclonal and monoclonal antibodies against alpha-gliadin in conjunction with 24 different food antigens and found significant immune reactivity when these antibodies were applied to dairy products and their components such as cow's milk, casein, whey, butyrophilin (a protein in milk found to cause an MS-like syndrome in an animal model), and milk chocolate. When various grains were tested, we found that both polyclonal and monoclonal antibodies prepared against alpha-gliadin reacted significantly with corn, millet, rice, and oats.
We concluded that for patients who do not show improvement in digestion or other symptoms on a gluten-free diet, attention should be given to various cross-reactive foods, such as dairy products, grains, and yeast. This intervention is ideally used in a phased approach. If patients do not initially improve on a gluten-free diet, they should be advised to remove cross-reactive foods. If they still do not improve after the elimination of dairy products, grains, and other reactive foods, it is important to check for other food intolerances. In some cases, symptoms may be associated with factors beyond cross-reactivity. Based on my communications with many clinicians, indications are that the majority of patients who had been diagnosed with non-celiac gluten sensitivity (NCGS) showed significant improvement in their symptomatologies after a gluten-free diet that also eliminated cross-reactive foods.
Testing for food cross-reactivity. Based on our research on cross-reactivity, the following lab panel was developed, which is available through Cyrex Laboratories (see www.CyrexLabs.com).
Array 4. Gluten-Associated Cross-Reactive Foods and Food Sensitivity
Rye, Barley, Spelt, Polish Wheat Sorghum IgG + IgA Combined
IgG + IgA Combined
Cow's Milk IgG + IgA Combined Millet IgG + IgA Combined
Alpha-Casein & Beta-Casein Hemp IgG + IgA Combined
IgG + IgA Combined
Casomorphin IgG + IgA Combined Amaranth IgG + IgA Combined
Milk Butyrophilin IgG + IgA Combined Quinoa IgG + IgA Combined
Whey Protein IgG + IgA Combined Tapioca IgG + IgA Combined
Chocolate (Milk) IgG + IgA Combined Teff IgG + IgA Combined
Oats IgG + IgA Combined Soy IgG + IgA Combined
Yeast IgG + IgA Combined Egg IgG + IgA Combined
Coffee IgG + IgA Combined Corn IgG + IgA Combined
Sesame IgG + IgA Combined Rice IgG + IgA Combined
Buckwheat IgG + IgA Combined Potato IgG + IgA Combined
This testing provides the opportunity to identify not only cross-reactive foods, but also additional reactive foods which are often recommended as substitutes or "safe" foods but which can be problematic to some gluten-sensitive patients (both celiac patients and non-celiac gluten-sensitive patients).
Dairy products. Research indicates that approximately 50% of all patients who have CD or NCGS are also dairy sensitive.10 Dairy sensitivity can generate symptoms similar to those of gluten sensitivity and can be another major factor in autoimmune disorders. Milk, for example, cross-reacts with islet cell antigens, which are involved in type 1 diabetes.
Coffee. Many people find it difficult to give up coffee. In one of our earlier experiments we had found that gliadin antibodies cross-reacted with instant coffee. Therefore, for this study we purchased coffee from Brazil, Colombia, Turkey, Israel, and Hawaii, and espresso from different coffeehouses.9 We were surprised to find that pure coffee did not cross-react with gluten. In repeat experiments we found that these antibodies did not react with pure coffee, but they did react with instant coffee. However, we do not know whether reactivity with instant coffee was a result of the manufacturing process or due to contaminants such as gluten or dairy at the manufacturing site.
Alcoholic beverages. Many patients are interested to know whether they can have whiskey or beer on a gluten-free diet. Our research has shown that distilled alcoholic beverages do not contain gluten or cross-reactive antigens. However, beer contains hundreds of gluten peptides. An Italian research team performed an elegant study evaluating various beers and found more than 150 different gliadin peptides in a single beer.11 Our own research included the evaluation of beers that claimed to be gluten-free, and we found some contamination. In short, distilled alcoholic beverages are gluten-free, but beer is not. This finding is in no way an endorsement of the consumption of distilled alcoholic beverages.
Wheat grass juice. It is important not to confound the issue of wheat germ and agglutinin with wheat grass. Approximately 2% of the dry protein of the wheat kernel consists of wheat germ agglutinin. In contrast, wheat grass juice is made from the green sprouts of the grain. We purchased wheat grass juice from three different sources and found that one of them was cross-reactive and two of them were not. Wheat grass in a pure form is not cross-reactive with alpha-gliadin. However, if one or two kernels of wheat are crushed into the juice during preparation, that can react with the antibodies. Only when the juice is contaminated does it cause immune reactivity with alpha-gliadin antibody.
Oats. The reactivity of oats depends on the variety of the grain. Some have an epitope (amino acid sequence in the DNA) that cross-reacts with alpha-gliadin, and other variants do not. How can we determine whether every food that we purchase contains gluten or not? In the past, the supposition was that reactivity was the result of contamination during manufacturing.
Research by an Italian group has shown that certain varieties of oats contain components of alpha-gliadin and others do not.12 This study indicated that reactivity is not just a matter of contamination, but occurs because of cross-breeding. Some varieties of oats carry a cross-reactive epitope that resembles the epitope of alpha-gliadin. Therefore, antibodies against alpha-gliadin cross-react with certain cultivars of oats, but not with others. Since there is currently no way to screen every variety of oats on the market for alpha-gliadin-type epitopes, the best approach for patients with CD or NCGS would be to consider oats cross-reactive and eliminate them from their diet.
Cross-Reactivity with Tissue
In our research, antibodies found to cross-react against alpha-gliadin also reacted significantly with a number of human tissues, including asialoganglioside, hepatocytes in the liver, glutamic acid decarboxylase (GAD-65) in the pancreas, adrenal 21 hydroxylase in adrenal glands, and various neuronal antigens (such as synapsin, myelin basic protein, and cerebellar).
Autism and cross-reactivity. The author performed a study eight years ago comparing antibody levels in children with autism with those of healthy controls, measuring antibodies against 12 different neural cell antigens including cerebellar antigen.13 Close to 25% of children with autism had antibodies against cerebellar and other neural antigens, while only 2% of children serving as controls had these antibodies. In another study, we demonstrated that alpha-gliadin cross-reacts with cerebellar due to a specific sequence of eight amino acids in cerebellar and in alpha-gliadin that are identical.6 This is the key mechanism of action in gluten ataxia and other forms of cerebellar degeneration. Although we do not know whether all the autistic children had cerebellar ataxia, we do know that if antibodies made against alpha-gliadin manage to cross the blood-brain barrier, the children may be at risk of developing ataxia in the future.
Predictive Antibodies in Autoimmunity
Researchers have identified more than 80 autoimmune conditions and suspect at least 40 more disorders of having an autoimmune basis. These conditions are chronic and many can be life-threatening.
The predictive function of antibodies. Research was conducted by the author several decades ago under an NIH grant to establish a test for measuring antibodies predictive of type 1 diabetes. We found that children developed antibodies against one or more components of islet cell antigens at least five to ten years before the onset of the disease. From this we learned that detection of tissue-specific antibodies could be used as an early biomarker of autoimmune disease.
Increasing predictive accuracy. A research protocol developed by A. L. Notkins, MD, an NIH immunologist, evaluated patients for diabetes risk by measuring antibodies against insulin, GAD-65 (glutamic acid decarboxylase), and islet cell antigens (protein tyrosine phosphatase).2 He found that measuring antibodies against just one antigen, such as insulin, the probability of predicting the disease was only 12%. When measuring antibodies against two antigens such as GAD-65 and PTP, the predictive accuracy increases to 50%. By measuring antibodies against all three of these antigens, predictive ability approaches 75%. The insight from this study is that the more tissue-specific antibodies we measure and the more antigens we identify, the better we can predict the risk of the disease.
This research provided further evidence of the "early warning" function of antibodies, concluding, "…predictive autoantibodies appear in the blood years before people show symptoms of various disorders. Tests that detected these molecules could warn of the need to take preventive action."2
The potentiating effect of antigens. Several articles published in scientific journals have reported that children with type 1 diabetes develop the disease much faster if put on baby formula containing cow's milk.3,4 While this does not constitute evidence that milk causes type 1 diabetes, the consensus in the literature is that the presence of dairy antigens potentiates the disease. If we remove that antigen from the diet, and immune potentiation does not occur, perhaps the development of autoimmune disease in that child will be delayed or avoided.
Correlation of antibodies and autoimmune reactivity. In patients with celiac disease (CD) or non-celiac gluten sensitivity (NCGS), it has been established that the probability of having one (or several) other autoimmune diseases is 30 times higher than in those who do not have these conditions. The incidence of gluten ataxia, for example, which manifests in disorders such as autism, is increased up to 30-fold in patients with celiac disease.5
In order to implement preventive measures, it is extremely important to identify antibody reactivity before significant tissue damage has occurred. If we detect autoimmunity at an early stage, we can help millions of people reverse the course of this disease.
Cross-Reactivity in Foods
The concept of cross-reactivity enables us to address factors beyond gluten sensitivity with targeted therapies. Cross-reactivity explains how immune sensitization to an antigen such as alpha-gliadin can trigger an immune attack against tissues and organs.
Immune sensitization and cross-reactivity. Gliadin is a prime example of an antigen that cross-reacts with other foods, as well as with human tissue antigens, causing symptoms of celiac disease beyond the gut.6 Food cross-reactivity is a sinister phenomenon that occurs as a result of the similarity in the sequence of amino acids in food proteins and in tissues and organs. Surprisingly, cross-reactivity can occur in a duplicate sequence involving as few as ten or so amino acids out of possibly hundreds.
Limitations of the gluten-free diet. It is widely reported in journal articles that patients with celiac disease frequently have abnormal villous atrophy,7 indicating complete destruction of certain gut tissues.Many clinicians have the impression that removing gluten from the diet will make a significant difference, reversing villous atrophy. However, research has found that when CD patients were put on a gluten-free diet, after six months only 8% of these patients had reversal of villous atrophy. An additional 65% of patients showed 50% improvement. The remaining 27% experienced no improvement in their clinical condition.8
Evaluating food cross-reactivity. We conducted a study to evaluate cross-reactivity between alpha-gliadin and extracts of numerous foods, including grains such as corn, millet, oats, and rice; dairy products; and other foods that are often recommended to patients on a gluten-free diet.9 The author tested this premise using two different sets of highly specific, purified antibodies made against alpha-gliadin 33-mer peptide, the major antigen causing celiac disease. One set of these antibodies consisted of polyclonal antibodies that were affinity purified, indicating that approximately 99% reacted with alpha-gliadin. All other reactive components had been removed to ensure that the antibodies were only reacting to the amino acid sequences of alpha-gliadin. In addition, highly specific monoclonal antibodies prepared against alpha-gliadin were utilized.
We tested the reactions of both the polyclonal and monoclonal antibodies against alpha-gliadin in conjunction with 24 different food antigens and found significant immune reactivity when these antibodies were applied to dairy products and their components such as cow's milk, casein, whey, butyrophilin (a protein in milk found to cause an MS-like syndrome in an animal model), and milk chocolate. When various grains were tested, we found that both polyclonal and monoclonal antibodies prepared against alpha-gliadin reacted significantly with corn, millet, rice, and oats.
We concluded that for patients who do not show improvement in digestion or other symptoms on a gluten-free diet, attention should be given to various cross-reactive foods, such as dairy products, grains, and yeast. This intervention is ideally used in a phased approach. If patients do not initially improve on a gluten-free diet, they should be advised to remove cross-reactive foods. If they still do not improve after the elimination of dairy products, grains, and other reactive foods, it is important to check for other food intolerances. In some cases, symptoms may be associated with factors beyond cross-reactivity. Based on my communications with many clinicians, indications are that the majority of patients who had been diagnosed with non-celiac gluten sensitivity (NCGS) showed significant improvement in their symptomatologies after a gluten-free diet that also eliminated cross-reactive foods.
Testing for food cross-reactivity. Based on our research on cross-reactivity, the following lab panel was developed, which is available through Cyrex Laboratories (see www.CyrexLabs.com).
Array 4. Gluten-Associated Cross-Reactive Foods and Food Sensitivity
Rye, Barley, Spelt, Polish Wheat Sorghum IgG + IgA Combined
IgG + IgA Combined
Cow's Milk IgG + IgA Combined Millet IgG + IgA Combined
Alpha-Casein & Beta-Casein Hemp IgG + IgA Combined
IgG + IgA Combined
Casomorphin IgG + IgA Combined Amaranth IgG + IgA Combined
Milk Butyrophilin IgG + IgA Combined Quinoa IgG + IgA Combined
Whey Protein IgG + IgA Combined Tapioca IgG + IgA Combined
Chocolate (Milk) IgG + IgA Combined Teff IgG + IgA Combined
Oats IgG + IgA Combined Soy IgG + IgA Combined
Yeast IgG + IgA Combined Egg IgG + IgA Combined
Coffee IgG + IgA Combined Corn IgG + IgA Combined
Sesame IgG + IgA Combined Rice IgG + IgA Combined
Buckwheat IgG + IgA Combined Potato IgG + IgA Combined
This testing provides the opportunity to identify not only cross-reactive foods, but also additional reactive foods which are often recommended as substitutes or "safe" foods but which can be problematic to some gluten-sensitive patients (both celiac patients and non-celiac gluten-sensitive patients).
Dairy products. Research indicates that approximately 50% of all patients who have CD or NCGS are also dairy sensitive.10 Dairy sensitivity can generate symptoms similar to those of gluten sensitivity and can be another major factor in autoimmune disorders. Milk, for example, cross-reacts with islet cell antigens, which are involved in type 1 diabetes.
Coffee. Many people find it difficult to give up coffee. In one of our earlier experiments we had found that gliadin antibodies cross-reacted with instant coffee. Therefore, for this study we purchased coffee from Brazil, Colombia, Turkey, Israel, and Hawaii, and espresso from different coffeehouses.9 We were surprised to find that pure coffee did not cross-react with gluten. In repeat experiments we found that these antibodies did not react with pure coffee, but they did react with instant coffee. However, we do not know whether reactivity with instant coffee was a result of the manufacturing process or due to contaminants such as gluten or dairy at the manufacturing site.
Alcoholic beverages. Many patients are interested to know whether they can have whiskey or beer on a gluten-free diet. Our research has shown that distilled alcoholic beverages do not contain gluten or cross-reactive antigens. However, beer contains hundreds of gluten peptides. An Italian research team performed an elegant study evaluating various beers and found more than 150 different gliadin peptides in a single beer.11 Our own research included the evaluation of beers that claimed to be gluten-free, and we found some contamination. In short, distilled alcoholic beverages are gluten-free, but beer is not. This finding is in no way an endorsement of the consumption of distilled alcoholic beverages.
Wheat grass juice. It is important not to confound the issue of wheat germ and agglutinin with wheat grass. Approximately 2% of the dry protein of the wheat kernel consists of wheat germ agglutinin. In contrast, wheat grass juice is made from the green sprouts of the grain. We purchased wheat grass juice from three different sources and found that one of them was cross-reactive and two of them were not. Wheat grass in a pure form is not cross-reactive with alpha-gliadin. However, if one or two kernels of wheat are crushed into the juice during preparation, that can react with the antibodies. Only when the juice is contaminated does it cause immune reactivity with alpha-gliadin antibody.
Oats. The reactivity of oats depends on the variety of the grain. Some have an epitope (amino acid sequence in the DNA) that cross-reacts with alpha-gliadin, and other variants do not. How can we determine whether every food that we purchase contains gluten or not? In the past, the supposition was that reactivity was the result of contamination during manufacturing.
Research by an Italian group has shown that certain varieties of oats contain components of alpha-gliadin and others do not.12 This study indicated that reactivity is not just a matter of contamination, but occurs because of cross-breeding. Some varieties of oats carry a cross-reactive epitope that resembles the epitope of alpha-gliadin. Therefore, antibodies against alpha-gliadin cross-react with certain cultivars of oats, but not with others. Since there is currently no way to screen every variety of oats on the market for alpha-gliadin-type epitopes, the best approach for patients with CD or NCGS would be to consider oats cross-reactive and eliminate them from their diet.
Cross-Reactivity with Tissue
In our research, antibodies found to cross-react against alpha-gliadin also reacted significantly with a number of human tissues, including asialoganglioside, hepatocytes in the liver, glutamic acid decarboxylase (GAD-65) in the pancreas, adrenal 21 hydroxylase in adrenal glands, and various neuronal antigens (such as synapsin, myelin basic protein, and cerebellar).
Autism and cross-reactivity. The author performed a study eight years ago comparing antibody levels in children with autism with those of healthy controls, measuring antibodies against 12 different neural cell antigens including cerebellar antigen.13 Close to 25% of children with autism had antibodies against cerebellar and other neural antigens, while only 2% of children serving as controls had these antibodies. In another study, we demonstrated that alpha-gliadin cross-reacts with cerebellar due to a specific sequence of eight amino acids in cerebellar and in alpha-gliadin that are identical.6 This is the key mechanism of action in gluten ataxia and other forms of cerebellar degeneration. Although we do not know whether all the autistic children had cerebellar ataxia, we do know that if antibodies made against alpha-gliadin manage to cross the blood-brain barrier, the children may be at risk of developing ataxia in the future.
Intestinal hyperpermeability. Increased intestinal permeability (leaky gut) is a major gateway to environmentally induced autoimmune disorders. This malfunction occurs, for example, in gluten-sensitive individuals when gluten and other cross-reactive or immunoreactive foods are consumed. In the gut, inflammation opens the tight junctions, allowing unwanted antigens into the bloodstream, including food proteins, fragments of normal gut flora, intestinal pathogens, and toxic chemicals such as alcohol or bisphenol A from plastics. The passage of reactive food proteins and other substances through the gut lining can have an immediate effect on dendritic cells and other immune cells located just below the gut lining. At that point, inflammatory cytokine production increases. The continuous stimulation of this process due to ongoing consumption of reactive foods is a major factor in the development of autoimmunity.
To evaluate the presence and severity of leaky gut, we measure antibodies against components of the tight junctions (actomyosin and occludin/zonulin) and lipopolysaccharides (endotoxins released due to an imbalance in the gut flora, intestinal dysbiosis, which causes the tight junctions to open). These endotoxins are oversized proteins, so their presence is a clear indication of hyperpermeability in the gut.14 Evaluations for hyperpermeability are provided in Cyrex Array 2, which tests for actomyosin IgA; occluding/zonulin IgA, IgG, and IgM; and lipopolysaccharides IgA, IgG, and IgM.
Breaching the blood-brain barrier. If inflammation becomes chronic, inflammatory cytokines and other factors can also open the blood-brain barrier (BBB). As a result, unwanted molecules (including dietary proteins and peptides, toxic chemicals, and even infectious agents or their antigens) gain access to the nervous system, causing damage to neural tissue and the release of neural antigens. These substances can sensitize the immune system, triggering reactivity against both these foreign materials and brain tissue. Over time the effects of this chronic inflammation can produce autoimmune symptoms that resemble multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neuroautoimmune disorders.
When the blood-brain barrier is intact, the only molecules that can penetrate are the size of glucose, exceptionally small molecules measuring approximately 160 daltons. In contrast, antigens are measured in kilodaltons, 10 to 10,000 times larger than glucose. The presence of gut-associated antigens in the blood is an indication of intestinal hyperpermeability. When the blood-brain barrier is opened under stress or neuroinflammatory conditions, these exceptionally large antigens can penetrate the nervous system along with immune cells. As a result, autoimmune reactivity to various triggers can occur within brain tissue or the nervous system in general, over a period of exposure from months to years.
Phases of Autoimmune Disorders
Autoimmunity is classified in three stages: stage 1, or silent autoimmunity, reflects the presence of antibodies; stage 2, or autoimmune reactivity, is characterized by the presence of antibodies with some associated symptomatology; and stage 3, or autoimmune disease, is differentiated by not only the presence of antibodies and symptoms, but also the loss of functionality.
Silent autoimmunity. Initially, autoimmune reactivity is classified as stage 1, characterized by elevated antibodies but no obvious symptoms or loss of function. Although this condition is referred to as silent, the ongoing production of antibodies targeted against tissues and organs can eventually induce some loss of function and the presentation of symptomatologies. It is therefore a predictor of future autoimmune disorders.
Autoimmune reactivity. As these conditions progress, elevated antibodies cause loss of function and discernible symptoms. Defined as stage 2, autoimmune reactivity has not yet resulted in the severe tissue destruction associated with the disease. Antigen-presenting cells and autoreactive T cells such as T-helper 1 and 17 attack and release various tissue antigens, stimulating B cells to produce antibodies. As tissue antigens are released, lymphocytes continue to react and B cells continue to produce antibodies. This process may continue over a period of three, five, or even ten years before tissue damage is detectable.
Autoimmune disease. When autoimmune reactivity persists, the disease becomes more advanced, with accompanying tissue damage and pathology. Damage occurs through the cumulative effects of autoreactive T-helpers 1 and 17, in tandem with antibodies and circulating immune complexes. This immune activity can cause significant damage, resulting in tissue dysfunction, which is detectable by imaging studies such as MRI. Once detectable damage occurs to various tissues such as brain, joints, thyroid, or pancreas, it is very difficult to reverse.
The development and progression of these disorders vary greatly from individual to individual. In fact, in some people this process may continue for years without major damage, while in others serious damage is detected within two to three years. In my opinion, autoimmunity should be detected at the earliest stage possible. If we wait five or ten years until full-blown autoimmune disease has developed, unfortunately, by that time the only choice clinicians have is to put the patient on immunosuppressive medication, corticosteroids, or monoclonal antibodies, which involve significant side effects. Conversely, the earlier we detect these conditions, the better we can help our patients. Currently the most effective intervention for these disorders is prevention through early detection of predictive antibodies.15
Triggers of Autoimmune Reactivity
For the clinician, it is not enough to simply detect and identify antibodies targeted against certain tissues or organs. It is also vital that we identify the mechanism of action triggering the development of tissue antibodies.
Gluten or cross-reactive foods. In conditions such as ataxia, for example, the immune system is reacting to the body's own cerebellar peptide because the patient is gluten sensitive and is producing antibodies against alpha-gliadin. Alpha-gliadin and cerebellar have a similar antigenic structure. If alpha-gliadin is cross-reacting with cerebellar, the solution is to remove gluten and cross-reactive foods from the diet, hence eliminating the source of autoimmune reactivity from the patient's environment.
Viral activation. Autoimmunity can also be triggered by reactivity to a dormant or sequestered virus. Epstein-Barr virus (EBV) provides a good example. Frequently, after viral infection, remnants of the virus remain in the body. When immune function is compromised due to injury, illness, or stress, the virus can be activated, and memory B cells reactive to EBV become activated to produce antibodies against EBV. Because the Epstein-Barr virus and neuronal cells have similar antigenic structures, if the antibodies cross the BBB, they will attack the nervous system, resulting in neurological symptoms such as multiple sclerosis. In these cases, by detecting and treating for EBV, it can be possible to prevent the progression of a condition such as MS.
Toxic chemicals. If toxins such as bisphenol A, heavy metals, or solvents bind to tissue, that tissue is then recognized as foreign material by the immune system. This is a common mechanism that triggers autoimmune reactivity against various tissue antigens. Chemicals that are lipophilic bind to fat tissue in the brain or to the myelin sheath, triggering autoimmune reactivity against neuronal tissue.
If this type of reactivity continues for more than five years, typically the result will be the loss of functionality in that tissue and the development of full-blown autoimmune disease.
Array 5: Multiple Autoimmune Reactivity Screen
The Multiple Autoimmune Reactivity Screen (MARS) measures 24 predictive antibodies, some of which can appear up to ten years before the clinical onset of disease. This panel includes antigens in the heart, liver, nervous system, gut, and joints, as well as endocrine tissue, thyroid, adrenal glands, and islet cells. The test can be used to detect not only full-blown autoimmune diseases but also the very early stages of autoimmunity. This is important because once a disease is fully developed, the efficacy of intervention is already extremely limited, but if reactive antibodies are detected early enough, then preemptive measures can be taken while organs and tissues are still functional.
Multiple Autoimmune Reactivity Screen (MARS)
Parietal Cell + ATPase IgG + IgA Fibulin IgG + IgA
Intrinsic Factor IgG + IgA Collagen Complex IgG + IgA
ASCA + ANCA IgG + IgA Arthritic Peptide IgG + IgA
Tropomyosin IgG + IgA Osteocyte IgG + IgA
Thyroglobulin IgG + IgA Cytochrome P450 (Hepatocyte) IgG + IgA
Thyroid Peroxidase (TPO) IgG + IgA Insulin + Islet Cell Antigen IgG + IgA
21 Hydroxylase (Adrenal Cortex) Glutamic Acid Decarboxylase 65
IgG + IgA (GAD 65) IgG + IgA
Myocardial Peptide IgG + IgA Myelin Basic Protein IgG + IgA
Alpha-Myosin IgG + IgA Asialoganglioside IgG + IgA
Phospholipid IgG + IgA Alpha + Beta Tubulin IgG + IgA
Platelet Glycoprotein IgG + IgA Cerebellar IgG + IgA
Ovary/Testis IgG + IgA Synapsin IgG + IgA
Individuals with one autoimmune disorder frequently develop additional autoimmune conditions; the genetic basis for this vulnerability has been described in the research literature.16,17 The detection of risk for additional autoimmune disorders in the future can be established by a simple blood test.
Multiple antigens indicating genetic risk. This screen economically and efficiently assesses the potential for possible tissue damage to multiple organs of the body. Autoimmune antibodies tend to be predictive; test results will indicate the involvement of various tissue antigens, and will correlate with risks for multiple potential autoimmune diseases in a given individual.
Multiple antigens due to leaky gut. When testing indicates significant levels of autoantibodies against five, six, or even ten different tissue antigens, it is vital to determine whether that patient is experiencing a problem with intestinal permeability. If leaky gut is present, we must first resolve this condition or we will not be able to reverse the course of autoimmune disease. We must evaluate the gut and blood-brain barriers, try to repair them, and explore potential environmental triggers. It is essential that we look deeper: is it the diet? Infectious agents? Toxic environmental chemicals? Unless we identify underlying exposures and triggers and remove them from the patient's environment, we will not be able to significantly help our patients.
Array 6: Diabetes Autoimmune Reactivity Screen
To date, two environmental triggers of type 1 diabetes have been identified. One is the coxsackievirus, which has almost 20% similarity with amino acid sequences in islet of Langerhans cells, as demonstrated in the research of J. Tian.18 When the coxsackievirus attacks islet cells, the immune system reacts against both the virus and islet cell antigens. This results in antibody production against GAD-65, islet cell antigens, or tyrosine phosphatase, and different chains of insulin. Subsequently, islet cells are gradually destroyed over a period of time, typically ranging from two to ten years, depending on the individual. The second environmental trigger that cross-reacts with islet cell antigens is milk and its associated antigens.3,19
Testing. Clinically these tests are intended for the early detection of autoimmune processes in type 1 diabetes, impaired blood sugar metabolism, and metabolic syndrome. It is noteworthy that some patients with type 2 diabetes also have type 1 diabetes. In these conditions, reactive T-helper 1 and T-helper 17 cells attack the islets of Langerhans, causing the release of insulin, glutamic acid decarboxylase (GAD-65), and protein tyrosine phosphatase (PTP). Therefore, in testing for autoimmune type 1 diabetes and for some cases of type 2 diabetes, the emphasis is on these three primary predictive antibodies: insulin, GAD-65, and PTP.
Tracking treatment effectiveness. This panel of testing can also be used to assess the effectiveness of treatment protocols in the management of autoimmune diabetes, and these tests are recommended for patients who have type 1 diabetes, a family history of type 1 diabetes, metabolic syndrome, or severe atypical manifestation of type 2 diabetes. GAD-65 antibodies are also found in many patients with other neuroautoimmune disorders, such as stiff-person syndrome or cerebellar ataxia. When there is the suspicion of gluten reactivity, dairy sensitivity, viral infection, and/or cerebellar ataxia, testing for insulin, GAD-65, and islet cell antigens can be beneficial for the patient. These tests are part of the Array 6 panel, Diabetes Autoimmune Reactivity Screen, offered by Cyrex Labs.
Conclusion
The prevalence of autoimmune disease is on the rise. Over the past four decades, many autoimmune disorders have increased three- and four-fold. These changes are not due to improved diagnostic criteria or increased recognition of autoimmunity. Rather, this crisis is due to factors in our environment, in particular, toxic chemicals. Due to exposure to these chemicals and the binding of chemicals or metabolites to human tissue, cellular defenses designed to protect the body attack the body's own tissues instead.
The empowering solution is to use predictive biomarkers to detect autoimmunity at the earliest stage possible, interrupting the progression of silent autoimmunity and autoimmune reactivity. "By making early intervention possible, predictive autoantibodies have the potential to alleviate much misery and to help provide extra years of healthy life."2 Then we can begin the process of cleaning up our bodies and our environment in order to reestablish immune homeostasis.
Researchers and clinicians should ask why the human body now reacts to its own antigens, which results in the production of potentially harmful autoantigens. The cause may be due to environmental factors such as bacterial or viral infections, or haptenic toxic chemicals binding to human tissue, causing modification of self-antigens and the subsequent production of autoantibodies. The final answer then for the prevention of autoimmune disease is to remove offending food antigens such as gluten from the diet of sensitive individuals; to pay attention to and maintain the balance of the gut microbiota; and to be wary of the viruses, pathogenic bacteria, and toxic chemicals that are responsible for the formation of neoantigens in our bodies.
"If we can detect autoimmune antibodies at an early stage, we can help millions of people reverse the course of autoimmune reactivity. By identifying disease triggers and removing them from the environment of the patient, I am confident that we can help millions of patients in America and worldwide stop or even reverse the course of their autoimmune reactivity."15
To evaluate the presence and severity of leaky gut, we measure antibodies against components of the tight junctions (actomyosin and occludin/zonulin) and lipopolysaccharides (endotoxins released due to an imbalance in the gut flora, intestinal dysbiosis, which causes the tight junctions to open). These endotoxins are oversized proteins, so their presence is a clear indication of hyperpermeability in the gut.14 Evaluations for hyperpermeability are provided in Cyrex Array 2, which tests for actomyosin IgA; occluding/zonulin IgA, IgG, and IgM; and lipopolysaccharides IgA, IgG, and IgM.
Breaching the blood-brain barrier. If inflammation becomes chronic, inflammatory cytokines and other factors can also open the blood-brain barrier (BBB). As a result, unwanted molecules (including dietary proteins and peptides, toxic chemicals, and even infectious agents or their antigens) gain access to the nervous system, causing damage to neural tissue and the release of neural antigens. These substances can sensitize the immune system, triggering reactivity against both these foreign materials and brain tissue. Over time the effects of this chronic inflammation can produce autoimmune symptoms that resemble multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neuroautoimmune disorders.
When the blood-brain barrier is intact, the only molecules that can penetrate are the size of glucose, exceptionally small molecules measuring approximately 160 daltons. In contrast, antigens are measured in kilodaltons, 10 to 10,000 times larger than glucose. The presence of gut-associated antigens in the blood is an indication of intestinal hyperpermeability. When the blood-brain barrier is opened under stress or neuroinflammatory conditions, these exceptionally large antigens can penetrate the nervous system along with immune cells. As a result, autoimmune reactivity to various triggers can occur within brain tissue or the nervous system in general, over a period of exposure from months to years.
Phases of Autoimmune Disorders
Autoimmunity is classified in three stages: stage 1, or silent autoimmunity, reflects the presence of antibodies; stage 2, or autoimmune reactivity, is characterized by the presence of antibodies with some associated symptomatology; and stage 3, or autoimmune disease, is differentiated by not only the presence of antibodies and symptoms, but also the loss of functionality.
Silent autoimmunity. Initially, autoimmune reactivity is classified as stage 1, characterized by elevated antibodies but no obvious symptoms or loss of function. Although this condition is referred to as silent, the ongoing production of antibodies targeted against tissues and organs can eventually induce some loss of function and the presentation of symptomatologies. It is therefore a predictor of future autoimmune disorders.
Autoimmune reactivity. As these conditions progress, elevated antibodies cause loss of function and discernible symptoms. Defined as stage 2, autoimmune reactivity has not yet resulted in the severe tissue destruction associated with the disease. Antigen-presenting cells and autoreactive T cells such as T-helper 1 and 17 attack and release various tissue antigens, stimulating B cells to produce antibodies. As tissue antigens are released, lymphocytes continue to react and B cells continue to produce antibodies. This process may continue over a period of three, five, or even ten years before tissue damage is detectable.
Autoimmune disease. When autoimmune reactivity persists, the disease becomes more advanced, with accompanying tissue damage and pathology. Damage occurs through the cumulative effects of autoreactive T-helpers 1 and 17, in tandem with antibodies and circulating immune complexes. This immune activity can cause significant damage, resulting in tissue dysfunction, which is detectable by imaging studies such as MRI. Once detectable damage occurs to various tissues such as brain, joints, thyroid, or pancreas, it is very difficult to reverse.
The development and progression of these disorders vary greatly from individual to individual. In fact, in some people this process may continue for years without major damage, while in others serious damage is detected within two to three years. In my opinion, autoimmunity should be detected at the earliest stage possible. If we wait five or ten years until full-blown autoimmune disease has developed, unfortunately, by that time the only choice clinicians have is to put the patient on immunosuppressive medication, corticosteroids, or monoclonal antibodies, which involve significant side effects. Conversely, the earlier we detect these conditions, the better we can help our patients. Currently the most effective intervention for these disorders is prevention through early detection of predictive antibodies.15
Triggers of Autoimmune Reactivity
For the clinician, it is not enough to simply detect and identify antibodies targeted against certain tissues or organs. It is also vital that we identify the mechanism of action triggering the development of tissue antibodies.
Gluten or cross-reactive foods. In conditions such as ataxia, for example, the immune system is reacting to the body's own cerebellar peptide because the patient is gluten sensitive and is producing antibodies against alpha-gliadin. Alpha-gliadin and cerebellar have a similar antigenic structure. If alpha-gliadin is cross-reacting with cerebellar, the solution is to remove gluten and cross-reactive foods from the diet, hence eliminating the source of autoimmune reactivity from the patient's environment.
Viral activation. Autoimmunity can also be triggered by reactivity to a dormant or sequestered virus. Epstein-Barr virus (EBV) provides a good example. Frequently, after viral infection, remnants of the virus remain in the body. When immune function is compromised due to injury, illness, or stress, the virus can be activated, and memory B cells reactive to EBV become activated to produce antibodies against EBV. Because the Epstein-Barr virus and neuronal cells have similar antigenic structures, if the antibodies cross the BBB, they will attack the nervous system, resulting in neurological symptoms such as multiple sclerosis. In these cases, by detecting and treating for EBV, it can be possible to prevent the progression of a condition such as MS.
Toxic chemicals. If toxins such as bisphenol A, heavy metals, or solvents bind to tissue, that tissue is then recognized as foreign material by the immune system. This is a common mechanism that triggers autoimmune reactivity against various tissue antigens. Chemicals that are lipophilic bind to fat tissue in the brain or to the myelin sheath, triggering autoimmune reactivity against neuronal tissue.
If this type of reactivity continues for more than five years, typically the result will be the loss of functionality in that tissue and the development of full-blown autoimmune disease.
Array 5: Multiple Autoimmune Reactivity Screen
The Multiple Autoimmune Reactivity Screen (MARS) measures 24 predictive antibodies, some of which can appear up to ten years before the clinical onset of disease. This panel includes antigens in the heart, liver, nervous system, gut, and joints, as well as endocrine tissue, thyroid, adrenal glands, and islet cells. The test can be used to detect not only full-blown autoimmune diseases but also the very early stages of autoimmunity. This is important because once a disease is fully developed, the efficacy of intervention is already extremely limited, but if reactive antibodies are detected early enough, then preemptive measures can be taken while organs and tissues are still functional.
Multiple Autoimmune Reactivity Screen (MARS)
Parietal Cell + ATPase IgG + IgA Fibulin IgG + IgA
Intrinsic Factor IgG + IgA Collagen Complex IgG + IgA
ASCA + ANCA IgG + IgA Arthritic Peptide IgG + IgA
Tropomyosin IgG + IgA Osteocyte IgG + IgA
Thyroglobulin IgG + IgA Cytochrome P450 (Hepatocyte) IgG + IgA
Thyroid Peroxidase (TPO) IgG + IgA Insulin + Islet Cell Antigen IgG + IgA
21 Hydroxylase (Adrenal Cortex) Glutamic Acid Decarboxylase 65
IgG + IgA (GAD 65) IgG + IgA
Myocardial Peptide IgG + IgA Myelin Basic Protein IgG + IgA
Alpha-Myosin IgG + IgA Asialoganglioside IgG + IgA
Phospholipid IgG + IgA Alpha + Beta Tubulin IgG + IgA
Platelet Glycoprotein IgG + IgA Cerebellar IgG + IgA
Ovary/Testis IgG + IgA Synapsin IgG + IgA
Individuals with one autoimmune disorder frequently develop additional autoimmune conditions; the genetic basis for this vulnerability has been described in the research literature.16,17 The detection of risk for additional autoimmune disorders in the future can be established by a simple blood test.
Multiple antigens indicating genetic risk. This screen economically and efficiently assesses the potential for possible tissue damage to multiple organs of the body. Autoimmune antibodies tend to be predictive; test results will indicate the involvement of various tissue antigens, and will correlate with risks for multiple potential autoimmune diseases in a given individual.
Multiple antigens due to leaky gut. When testing indicates significant levels of autoantibodies against five, six, or even ten different tissue antigens, it is vital to determine whether that patient is experiencing a problem with intestinal permeability. If leaky gut is present, we must first resolve this condition or we will not be able to reverse the course of autoimmune disease. We must evaluate the gut and blood-brain barriers, try to repair them, and explore potential environmental triggers. It is essential that we look deeper: is it the diet? Infectious agents? Toxic environmental chemicals? Unless we identify underlying exposures and triggers and remove them from the patient's environment, we will not be able to significantly help our patients.
Array 6: Diabetes Autoimmune Reactivity Screen
To date, two environmental triggers of type 1 diabetes have been identified. One is the coxsackievirus, which has almost 20% similarity with amino acid sequences in islet of Langerhans cells, as demonstrated in the research of J. Tian.18 When the coxsackievirus attacks islet cells, the immune system reacts against both the virus and islet cell antigens. This results in antibody production against GAD-65, islet cell antigens, or tyrosine phosphatase, and different chains of insulin. Subsequently, islet cells are gradually destroyed over a period of time, typically ranging from two to ten years, depending on the individual. The second environmental trigger that cross-reacts with islet cell antigens is milk and its associated antigens.3,19
Testing. Clinically these tests are intended for the early detection of autoimmune processes in type 1 diabetes, impaired blood sugar metabolism, and metabolic syndrome. It is noteworthy that some patients with type 2 diabetes also have type 1 diabetes. In these conditions, reactive T-helper 1 and T-helper 17 cells attack the islets of Langerhans, causing the release of insulin, glutamic acid decarboxylase (GAD-65), and protein tyrosine phosphatase (PTP). Therefore, in testing for autoimmune type 1 diabetes and for some cases of type 2 diabetes, the emphasis is on these three primary predictive antibodies: insulin, GAD-65, and PTP.
Tracking treatment effectiveness. This panel of testing can also be used to assess the effectiveness of treatment protocols in the management of autoimmune diabetes, and these tests are recommended for patients who have type 1 diabetes, a family history of type 1 diabetes, metabolic syndrome, or severe atypical manifestation of type 2 diabetes. GAD-65 antibodies are also found in many patients with other neuroautoimmune disorders, such as stiff-person syndrome or cerebellar ataxia. When there is the suspicion of gluten reactivity, dairy sensitivity, viral infection, and/or cerebellar ataxia, testing for insulin, GAD-65, and islet cell antigens can be beneficial for the patient. These tests are part of the Array 6 panel, Diabetes Autoimmune Reactivity Screen, offered by Cyrex Labs.
Conclusion
The prevalence of autoimmune disease is on the rise. Over the past four decades, many autoimmune disorders have increased three- and four-fold. These changes are not due to improved diagnostic criteria or increased recognition of autoimmunity. Rather, this crisis is due to factors in our environment, in particular, toxic chemicals. Due to exposure to these chemicals and the binding of chemicals or metabolites to human tissue, cellular defenses designed to protect the body attack the body's own tissues instead.
The empowering solution is to use predictive biomarkers to detect autoimmunity at the earliest stage possible, interrupting the progression of silent autoimmunity and autoimmune reactivity. "By making early intervention possible, predictive autoantibodies have the potential to alleviate much misery and to help provide extra years of healthy life."2 Then we can begin the process of cleaning up our bodies and our environment in order to reestablish immune homeostasis.
Researchers and clinicians should ask why the human body now reacts to its own antigens, which results in the production of potentially harmful autoantigens. The cause may be due to environmental factors such as bacterial or viral infections, or haptenic toxic chemicals binding to human tissue, causing modification of self-antigens and the subsequent production of autoantibodies. The final answer then for the prevention of autoimmune disease is to remove offending food antigens such as gluten from the diet of sensitive individuals; to pay attention to and maintain the balance of the gut microbiota; and to be wary of the viruses, pathogenic bacteria, and toxic chemicals that are responsible for the formation of neoantigens in our bodies.
"If we can detect autoimmune antibodies at an early stage, we can help millions of people reverse the course of autoimmune reactivity. By identifying disease triggers and removing them from the environment of the patient, I am confident that we can help millions of patients in America and worldwide stop or even reverse the course of their autoimmune reactivity."15
Aristo Vojdani, PhD
Aristo Vojdani is presently a professor of neuroimmunology at the Carrick Institute for Graduate Studies and is a past associate professor at the Charles Drew/UCLA School of Medicine and Science. He obtained his MSc and PhD in the field of microbiology and clinical immunology with postdoctoral studies in tumor immunology at UCLA. His ongoing research, spanning a 45-year career, focuses on the role of environmental triggers such as toxic chemicals, infections, and dietary proteins and peptides, in complex diseases. Professor Vojdani's research and focus on predictive antibodies has resulted in the development of numerous antibody arrays for the detection of many autoimmune disorders. Of particular note are the arrays for autoimmune diseases that originate from the gut and manifest as attacks on the body's own tissues or organs, including the brain. An owner of 15 US patents for laboratory assessments, Professor Vojdani has published more than 130 articles in scientific journals. He is the CEO and Technical Director of Immunosciences Lab., Inc. in Los Angeles, California, and is the Chief Scientific Advisor for Cyrex Labs LLC, in Phoenix, Arizona. He sits on the editorial board of five scientific journals. In 2006, he was given the prestigious Herbert J. Rinkel Award by the American Academy of Environmental Medicine (AAEM) for excellence in teaching the techniques of environmental medicine. In 2009, he received the Linus Pauling, PhD Award by the American College for Advancement in Medicine, and in 2012 he was given the F. R. Carrick Research Institute's extremely distinguished Lifetime Achievement Award.
Aristo Vojdani is presently a professor of neuroimmunology at the Carrick Institute for Graduate Studies and is a past associate professor at the Charles Drew/UCLA School of Medicine and Science. He obtained his MSc and PhD in the field of microbiology and clinical immunology with postdoctoral studies in tumor immunology at UCLA. His ongoing research, spanning a 45-year career, focuses on the role of environmental triggers such as toxic chemicals, infections, and dietary proteins and peptides, in complex diseases. Professor Vojdani's research and focus on predictive antibodies has resulted in the development of numerous antibody arrays for the detection of many autoimmune disorders. Of particular note are the arrays for autoimmune diseases that originate from the gut and manifest as attacks on the body's own tissues or organs, including the brain. An owner of 15 US patents for laboratory assessments, Professor Vojdani has published more than 130 articles in scientific journals. He is the CEO and Technical Director of Immunosciences Lab., Inc. in Los Angeles, California, and is the Chief Scientific Advisor for Cyrex Labs LLC, in Phoenix, Arizona. He sits on the editorial board of five scientific journals. In 2006, he was given the prestigious Herbert J. Rinkel Award by the American Academy of Environmental Medicine (AAEM) for excellence in teaching the techniques of environmental medicine. In 2009, he received the Linus Pauling, PhD Award by the American College for Advancement in Medicine, and in 2012 he was given the F. R. Carrick Research Institute's extremely distinguished Lifetime Achievement Award.
Cyrex Laboratories
Cyrex™ is a clinical immunology laboratory specializing in autoimmunity. The lab offers multi-tissue antibody testing for the early detection and monitoring of today's complex autoimmune conditions. Cyrex develops innovative arrays through continuous collaboration with leading experts in medical research and clinical practice. For additional information, see www.CyrexLabs.com.
Cyrex™ is a clinical immunology laboratory specializing in autoimmunity. The lab offers multi-tissue antibody testing for the early detection and monitoring of today's complex autoimmune conditions. Cyrex develops innovative arrays through continuous collaboration with leading experts in medical research and clinical practice. For additional information, see www.CyrexLabs.com.
Cyrex
5040 N. 15th Avenue, Suite 107
Phoenix, Arizona 85015
602-759-1245; Fax 602-759-8331
5040 N. 15th Avenue, Suite 107
Phoenix, Arizona 85015
602-759-1245; Fax 602-759-8331
Editorial
Nancy Faass, MSW, MPH, is a writer in San Francisco who has worked on more than 40 books; she also provides articles, white papers, and writing for the Web via www.HealthWritersGroup.com. Thanks to Jerry Stine, NC, for technical support on this article; see www.Lifespan-Institute.com.
Nancy Faass, MSW, MPH, is a writer in San Francisco who has worked on more than 40 books; she also provides articles, white papers, and writing for the Web via www.HealthWritersGroup.com. Thanks to Jerry Stine, NC, for technical support on this article; see www.Lifespan-Institute.com.
References
1 National Institutes of Health, The Autoimmune Diseases Coordinating Committee. Progress in autoimmune diseases research. Report to Congress. Published March 2005.
2 Notkins AL. New predictors of disease. Sci Am. 2007 296(3):72-79.
3 Virtanen M, et al. Cow 's milk consumption, HLA-DQB1 genotype, and type 1 diabetes. A nested case-control study of siblings of children with diabetes. Diabetes. 2000 49:912-917.
4 Karjalainen J, et al. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. NEJM. 1992 327(5):302-307.
5 Vojdani A, et al. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci. 2004 7(3):151-161.
6 Vojdani A, et al. The immunology of gluten sensitivity beyond the intestinal tract. Eur J Inflmm. 2008 6(2):49-57.
7 Ludvigsson JF, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013 62:43-52.
8 Lanzini A, et al. Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet. Aliment Pharmacol Thera. 2009 29(12):1299-1308. doi:10.1111/j.1365-2036.2009.03992.x
9 Vojdani A, Tarash I. Cross-reaction between gliadin and different food and tissue antigens. FNS. 201344:20-32.
10 Kristjansson G, et al. Mucosal reactivity to cow's milk protein in coeliac disease." Clin Exp Immunol. 2007 147(3):449-455. doi:10.1111/j.1365-2249.2007.03298.x
11 Comino I, et al. Immunological determination of gliadin 33-mer equivalent peptides in beers as a specific and practical analytical method to assess safety for celiac patients. J Sci Food Agric. 2013 93(4):933-943. doi: 10.1002/jsfa.5830
12 Comino I, et al. Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease." Gut. 2011 60(7):915-922. doi:10.1136/gut.2010.225268
13 Vojdani A, et al. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus Group A. J Neuroimmunol. 2002 129:168-177.
14 Vojdani A. For the assessment of intestinal permeability, size matters. Alter Ther Health Med. 2013 19(1):12-24.
15 Vojdani A. Antibodies as predictors of autoimmune diseases and cancer. Expert Opinion on Medical Diagnostics. 2008 2(6):593-605.
16 Devraj B, et al. Molecular basis for recognition of an arthritic peptide and a foreign epitope on distinct MHC molecules by a single TCR. J Immunol. 2006 164:5788-5796.
17 Betterle C, et al. Update on autoimmune polyendocrine syndromes (APS). Acta Bio Medica. 2003 74:9-33.
18 Tian J, et al. T cell cross-reactivity between coxsackie virus and glutamate decarboxylase is associated with a murine susceptibility allele. J Exp Med. 1994 180(5):1979-1984.
19 Cavallo MG, et al. Cell-mediated immune response to beta casein in recent-onset insulin-dependent diabetes: implications for disease pathogenesis. Lancet. 1996 348:926-928.
1 National Institutes of Health, The Autoimmune Diseases Coordinating Committee. Progress in autoimmune diseases research. Report to Congress. Published March 2005.
2 Notkins AL. New predictors of disease. Sci Am. 2007 296(3):72-79.
3 Virtanen M, et al. Cow 's milk consumption, HLA-DQB1 genotype, and type 1 diabetes. A nested case-control study of siblings of children with diabetes. Diabetes. 2000 49:912-917.
4 Karjalainen J, et al. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. NEJM. 1992 327(5):302-307.
5 Vojdani A, et al. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci. 2004 7(3):151-161.
6 Vojdani A, et al. The immunology of gluten sensitivity beyond the intestinal tract. Eur J Inflmm. 2008 6(2):49-57.
7 Ludvigsson JF, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013 62:43-52.
8 Lanzini A, et al. Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet. Aliment Pharmacol Thera. 2009 29(12):1299-1308. doi:10.1111/j.1365-2036.2009.03992.x
9 Vojdani A, Tarash I. Cross-reaction between gliadin and different food and tissue antigens. FNS. 201344:20-32.
10 Kristjansson G, et al. Mucosal reactivity to cow's milk protein in coeliac disease." Clin Exp Immunol. 2007 147(3):449-455. doi:10.1111/j.1365-2249.2007.03298.x
11 Comino I, et al. Immunological determination of gliadin 33-mer equivalent peptides in beers as a specific and practical analytical method to assess safety for celiac patients. J Sci Food Agric. 2013 93(4):933-943. doi: 10.1002/jsfa.5830
12 Comino I, et al. Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease." Gut. 2011 60(7):915-922. doi:10.1136/gut.2010.225268
13 Vojdani A, et al. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus Group A. J Neuroimmunol. 2002 129:168-177.
14 Vojdani A. For the assessment of intestinal permeability, size matters. Alter Ther Health Med. 2013 19(1):12-24.
15 Vojdani A. Antibodies as predictors of autoimmune diseases and cancer. Expert Opinion on Medical Diagnostics. 2008 2(6):593-605.
16 Devraj B, et al. Molecular basis for recognition of an arthritic peptide and a foreign epitope on distinct MHC molecules by a single TCR. J Immunol. 2006 164:5788-5796.
17 Betterle C, et al. Update on autoimmune polyendocrine syndromes (APS). Acta Bio Medica. 2003 74:9-33.
18 Tian J, et al. T cell cross-reactivity between coxsackie virus and glutamate decarboxylase is associated with a murine susceptibility allele. J Exp Med. 1994 180(5):1979-1984.
19 Cavallo MG, et al. Cell-mediated immune response to beta casein in recent-onset insulin-dependent diabetes: implications for disease pathogenesis. Lancet. 1996 348:926-928.
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