Should you be concerned about autoimmunity?

One of the basic functions of the immune system is to recognize and eliminate foreign antigens or intruders such as viruses and bacteria in order to protect the body from their harmful actions. The immune system creates antibodies in response to an antigen. This process provides protective immunity that is a part of the normal function of the immune system.

Autoimmunity is an over reactive response of the immune system against an antigen. The combination of three factors could lead to development of an autoimmune disease: a genetic predisposition, target organ(s) and an environmental trigger(s) that cause the immune system to overreact and attack its own healthy tissue.

Genetic predisposition

Autoimmune diseases and their related genes can run in the families, however, genetically predisposed individuals do not always develop autoimmune diseases and if they do, the same genes do not always cause the same disease.

The immune system maintains a balance between too little and over reactive response to an intruder. A too low response of the immune system leads to potential danger that is caused by an antigen.  Further more, an over reactive response can potentially lead to damage of the healthy tissues. Genetic predisposition to over react exists in all individuals with autoimmune disease and may be similar in many different autoimmune diseases.

However, autoimmunity does not necessarily lead to tissue damage. Autoantibodies, such as rheumatoid factor or antinuclear antibodies occur in more than 5% of people without ever resulting in rheumatoid arthritis or systemic lupus erythenatosus, which are characterized by presence of such antibody over reactivity. Autoimmune disease occurs when the organism allows immune response against its own healthy organs causing damage or destruction.

Another risk factor for autoimmunity could be a defect in restoration of immune system to the previous stable condition. After the immune response to the antigen the immune system fails to use its down regulation mechanisms to restore its balance. The process of calming down of the immune reaction is  controlled and mediated by multiple inhibitory pathways. A major component of autoimmune disease in some individuals may be a defect in the suppression of immune activation.

Target organs

Autoimmune disease requires not just over reactivity of the immune system, but also target organ vulnerability. The attack can target any area of the body, however the disease is most likely to affect the weakest organ. In the organ specific autoimmune diseases antibodies act against the antigens in a particular organ or tissue. Type 1 diabetes mellitus, multiple sclerosis, autoimmune thyroiditis, pernicious anemia, hepatitis and vitiligo are examples of organ specific autoimmune diseases.

Autoimmunity can damage nearly every tissue or cell type of the body. Often the over reacting immune system may attack not only one organ but have several targets as it occurs in lupus, rheumatoid arthritis, scleroderma, Sjorgen’s syndrome, psoriasis, inflammatory bowel disease and polygrandular disorders. These diseases involve a diverse array of clinical symptoms that potentially involve multiple organ systems.

The genetic factors that cause over reactivity of the immune system and specific organ vulnerability are different. This fact could be the reason why individuals with similar pathways of over reactivity develop different autoimmune diseases. For example, one family member may have immune cells that react against thyroid, while another may suffer an autoimmune attack on the joints. Even among identical twins, the chances of developing the same autoimmune disease can vary.

Many of the autoimmune diseases share the same antibodies, feature tissue or organ destruction caused by the same immune cells or have common genes affected. The same susceptibility genes can contribute to development of different autoimmune diseases. For example, inflammatory bowel disease and psoriasis are associated with the same gene. The difference why the disease develops in one way or another may lie in the genes which are responsible for the target organ susceptibility or in the genes that modulate disease severity.

Environmental factors

Environmental factors are also important triggers of autoimmunity. Drug and chemical exposure, diet, and lack of sunlight have all been identified as risk factors for particular diseases. Presence of gluten and/or excess of iodine in the diet may trigger autoimmune thyroiditis in genetically predisposed individuals.

Antigen exposure or infection such as bacterial, viral and parasitic infections can initiate and exacerbate autoimmune disease. Certain infections participate in the development of particular autoimmune diseases.  The associations between lupus and Epstein-Barr virus (EBV) infection, pediatric autoimmune neuropsychiatric disorders and streptococcal infection, hepatitis C virus (HCV) and autoimmune thyroid diseases are well documented. However, for some autoimmune diseases there is a combination of more than one trigger possible.

Cigarette smoking and thyroid diseaseCigarette smoking has been linked to the development of multiple autoimmune diseases such as rheumatoid arthritis, systemic lupus, multiple sclerosis, Graves’ disease and primary biliary cirrhosis. The combination of interactions between cigarette smoking, genetic and immunologic factors affect the action of the immune system and is a well known trigger of autoimmune diseases.

In medium- or high-latitude countries a lack of sunshine causes low level of  vitamin D in the general population. A number of autoimmune diseases, including multiple sclerosis, type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis, are associated with vitamin D deficiency. However, the lack of vitamin D could be one of many risk factors.

There are more studies suggesting that a combination of a multiple factors initiate autoimmunity. The numerous other environmental triggers and genetic risk factors appear to interact and combine to trigger the thyroid autoimmune diseases and multiple sclerosis. In systemic lupus, factors such as UV light and drugs, including estrogen, may trigger the disease.

 

Hormones and autoimmunity

Hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Hormone balance is altered among patients with autoimmune disease, and this variation of imbalance contributes to immune disregulation.

The enhanced immunoreactivity in females provides better protection against infections, but at the same time may lead to enhanced auto reactivity and thereby contribute to the induction of autoimmunity. Hormonal imbalances in young women and hormonal changes around menopause can contribute to the thyroid autoimmunity and Hashimoto’s disease.

Autoimmune diseases are approximately three times more common in women than in men. Some thyroid, rheumatic, and hepatic autoimmune diseases have high female to male ratios, whereas others have low. Autoimmune diseases represent the fifth leading cause of death by disease among females of reproductive age.

Not all autoimmune diseases are more common in women. Some of them, such as ankylosing spondylitis, have a much higher incidence in men. Predisposition to autoimmunity can be sex determined or hormonally modulated. Thus the higher incidence of disease in women may not always reflect the influence of female hormones on the immune system. The evidence also shows that the effects of sex hormones differ in different diseases. While there is a significant evidence that estrogen can exacerbate systemic lupus, estrogen seems to protect against rheumatoid arthritis.

New studies conducted by Prof. Alessio Fasano introduced a new model that explains the autoimmunity from a new prospective and suggests that autoimmune disease can be not only stopped and reversed but also prevented.

According to the Prof. Fasano, there is a third components of autoimmunity that if present allows the environmental triggers to turn certain genes on and cause the disease. Read  more

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References:

The autoimmune connection: Essential information for women on diagnosis, treatment, and getting on with your life by Rita Baron-Faust, Jill P. Buyon, McGraw-Hill Professional, 2004, p. 7-12

The autoimmune diseases by Ian R. Mackay, Academic Press, 2006, p.26-28

Cigarette smoking and autoimmune disease: what can we learn from epidemiology? Costenbader K.H, Karlson E.W. Lupus. 2006;15(11):737-45

Autoimmune diseases associated with drugs, chemicals and environmental factors. D’Cruz D. Toxicol Lett. 2000 Mar 15;112-113:421-32

Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Pierrot-Deseilligny C, Souberbielle JC. Brain. 2010 Jul;133(Pt 7):1869-88