What role do chronic bacterial and viral infections play in autoimmunity? What role do environmental toxins play? The role of the glutathione and nitric oxide synthase (NOS) systems and development of autoimmunity.
Main points of this issue:
- Evidence shows that chronic bacterial or viral infections play a role in the development of autoimmune disease
- Various viruses, such as coxsackie virus, herpes simplex 1 virus, Epstein-Barr virus, and adenoviruses have been associated with the development of autoimmune disease
- Protozoan infections have been linked to intestinal permeability
- Exposure to persistent organic pollutants (POPs) has been linked to the development of autoimmune diabetes (type I diabetes)
- Bisphenol A (BPA) is one of the most well-known and toxic POPs
- BPA is common in plastic food and bevarage containers
- BPA acts as a potent estrogen in the body and has been linked to several immune-mediated diseases, cancer and infections
- Environmental compounds activate the immune system only after glutathione levels are depleted
- Failure of the glatathione system causes immune activation
- Immune activation triggers inducible nitric oxide synthase (iNOS) which promotes autoimmunity.
The origins of autoimmune disease are multifactorial
“The origins of autoimmune disease are multifactorial. Environmental factors and a genetic predisposition result in tissue injury caused by autoreactive T cells or antibodies.”1
We know that there are a number of physiologic dysfunctions and overzealous immune responses that are involved in the development of autoimmune disease. We looked at some of these dysfunctions in the last issue, including intestinal permeability and gluten sensitivity. In this issue, we focus on other mediators and modulating factors involved in the development of autoimmunity, including chronic bacterial, viral or parasitic infection and environmental exposures, such as BPA and other persistent organic pollutants. We will also look at the role glutathione plays in protecting us from autoimmunity, and how the glutathione recycling system and the nitric oxide system are so important in preventing autoimmune disease.
It is important to keep in mind that the development of autoimmune disease does not occur overnight. The manifestations of the disease occur much later than the initiating factors that lead to the development of autoimmunity. During this time, patients are often asymptomatic and unaware that they are laying the groundwork for the development of autoimmunity (immune response to self-tissue).
“Autoimmune diseases tend to have long, asymptomatic prodromal periods and the initiating events leading to loss of self tolerance occur long before the disease becomes clinically manifest.”2
What are Some of the Mediators/Modulating Factors that Contribute to Autoimmunity?
Chronic Infection and Chronic Inflammation
There is more and more evidence of the role that chronic bacterial or viral infections play in the development of autoimmune disease.
“Emerging evidence has suggested the involvement of environmental factors such as infections and xenobiotics, and some dietary proteins and their antibodies in the pathogenesis of many autoimmune diseases”.3
“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”.4
Coxsackie Virus and Autoimmune Diabetes (Type 1 Diabetes)
“Three way molecular mimicry exists between a peptide of carboxypeptidase H (an enzyme expressed within islet cell granules and an autoantigen), and peptides of coxsackie virus coat protein.”
“The major peptide determinant of GAD recognized by patients with diabetes has a significant sequence similarity to a 15 amino acid sequence within a protein of coxsackie B virus. Antibodies to this protein cross react with GAD 65 and vice versa, suggesting that molecular mimicry might be responsible for the disease.”5
Herpes Simplex Virus 1 and Epstein-Barr Virus
“Another islet cell antigen, ICA 512 has similarities with peptides in human herpes virus 1 (herpes simplex virus 1) and 4 (Epstein-Barr virus)”.6
Celiac Disease and Adenovirus Antibodies
“89% of untreated celiac patients had antibodies to adenovirus 12, and these antibodies were also raised in treated children with celiac disease (31%) compared with controls (0-13%)”
“It is possible that infection with adenovirus sensitizes the genetically predisposed host to A-gliadin by molecular mimicry, with resultant gluten sensitive enteropathy, using the hit and run mechanism.”7
Protozoan Infection and Intestinal Permeability
Certain protozoan infections, such as giardia and Blastocystis hominis, have been linked with the development of intestinal permeability:
“39 patients with protozoan infections were compared to 10 healthy controls. Intestinal permeability was found to be increased in patients with protozoan infections compared with the control patients. Specifically, intestinal permeability was increased in the Giardia and Blastocystis groups, although not in the Entamoeba coli group. The increase in intestinal permeability in patients with Blastocystis hominis suggests that it can be a pathogenic protozoal infection and have systemic consequences.”8
What are Some of the Mediators/ Modulating Factors that Contribute to Autoimmunity?
Drugs and Environmental Compounds
“Autoimmune reaction or autoimmune disease may be induced by drugs and chemical xenobiotics, which have the potential to form complexes with or otherwise alter self-proteins such that they become immunogenic (targets of immune attack).”9
Persistent Organic Pollutants (POPs) and Autoimmune Disease
“Persistent organic pollutants (POPs) include hundreds of different chemical compounds with common properties, such as long-term persistence, widespread diffusion in the environment and bioaccumulation through the food chain.”10
“Exposure to relatively high levels of POPs during pancreatic development in utero or in early infancy may lead to the development of type 1 diabetes among children.”11
Bisphenol A (BPA) and Autoimmune Disease
One of the most well-known and toxic of these POPs is bisphenol A (BPA). BPA is commonly used by the food industry in plastic food and bevarage containers and in the lining of canned foods.
“The precise mechanism underlying the immunomodulatory effects of Endocrine Disrupting Chemicals (EDCs), especially BPA, has not been clarified, and multiple mechanisms are considered.”12
“Some of these studies were prompted by concern that xenoestrogens may contribute to development of autoimmune disease.”13
“BPA is not only an estrogen mimic but also may exhibit a mechanism of action similar to that of the sex hormone at the receptor. Therefore, considerable attention has focused on this environmental estrogen-like chemical, which may affect reproductive organs.”14
“The ubiquitous estrogenic chemical bisphenol A (BPA) is the base chemical used to make polycarbonate plastic food and beverage containers, the resin lining of cans, and dental sealants; it also is found in ‘carbonless’ paper used for receipts as well as a wide range of other common household products.”15
“It appears to be undeniable that at least part of the immune system, especially Th1 responses, may be modulated by either prenatal or postnatal exposure to the environmental estrogen-like chemical, BPA.”16
“The effects of BPA on cells confirm that BPA acts as a potent estrogen via this recently discovered estrogen response pathway.”17
“BPA and estradiol are also equipotent at inhibiting adiponectin release from human adipocytes, further implicating BPA at current human exposure levels in insulin resistance and the metabolic syndrome.”18
“The decrease of T reg cells would predispose to immune dysfunction in aged individuals, explaining their higher risk of immune-mediated diseases, cancer, and infections. Our data also suggest the possibility that BPA might cause these diseases.”19
“Thus, avoiding exposure to or promoting the excretion of BPA and other EDCs would help in preventing diseases and adverse health effects.”20
Environmental Compounds and Glutathione Depletion
The other thing we know is that an environmental compound activates the immune system only after glutathione levels are depleted in the body. Glutathione, which is produced by the liver, is considered the bodys most important antioxidant. Glutathione is the main antioxidant that protects cellular mitochondria. Glutathione “takes the bullet” from the free radical to protect the mitochondria. If this system fails and you dont have this system to take the bullet, then you get immune activation.
“Environmental exposures start depleting glutathione which leads to immune activation which activates iNOS and promotion of autoimmunity. These results suggest that TBT (an environmental pollutant), selectively induces apoptosis and T helper polarity via generation of hydrogen peroxide because of low GSH (glutathione) levels.”21
A healthy glutathione system is a prerequisite in order to prevent autoimmunity. We all have this glutathione system that allows us to not respond to, or end up responding to, an environmental hapten (chemical) exposure. If this system fails, then you get immune activation. Immune activation then triggers inducible nitric oxide synthase (iNOS) which causes tissue destruction and promotes autoimmunity. We will discuss these systems in more depth in the next segment.
Content provided by Datis Kharrazian, D.C., Autoimmune Regulation of the Nitric Oxide and Glutathione Systems, 11/4/10
In part 5 of this 6-part series, we answer the following questions:
- How do we modulate the autoimmune response?
- What role do the glutathione and nitric oxide synthase (NOS) systems play in preventing and modulating AI disease?
- What role does vitamin D play?
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