Autoimmune Disease: not so Rare Disease!
Autoimmune Disease: not so Rare Disease!
  • Professor You-Me Kim
  • 승인 2014.12.03 07:29
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Our immune system protects our body from an infinite array of invading pathogens using antibodies and specialized immune cells. The immune system is designed to kill and remove harmful microbes such as bacteria, viruses, and fungi without hurting our own cells and tissues. This feat is possible because of the immune system’s unique ability to distinguish our own ‘self’ molecules from the ones derived from dangerous microbes that are ‘non-self’. In other words, the immune system is programmed to be ‘tolerant’ to self. However, B cells and T cells, which are the most important immune cell types of our body, lack the intrinsic ability to discriminate the self from the non-self. Instead, during development in bone marrow and thymus, individual B cells and T cells that display reactivity to self molecules are forced to die or are ‘deleted’, and are not released to peripheral tissues, thereby preventing their attack of our own body. This is the most crucial mechanism for establishing the self-tolerance. Unfortunately, this process is imperfect and, as a result, all of us have potentially self-reactive immune cells circulating in our blood. Most of the time, however, these self-reactive immune cells are kept under check by various safety mechanisms. Autoimmune disease occurs when self-reactive or ‘autoreactive’ B and T cells escape the suppression and become activated. Activated autoreactive B cells and T cells secrete autoantibodies, which are antibodies binding to self molecules or ‘autoantigens’, destroy our own cells and tissues, and sometimes cause fatal organ failures. 
So far, about a hundred different types of autoimmune diseases are identified, many of which share common symptoms, making a precise diagnosis difficult. In general, autoimmune diseases can be classified into the ‘organ-specific’ disorders and the ‘systemic’ disorders. The organ-specific autoimmune diseases develop due to the unrestrained activation of immune cells responding to autoantigens that are found in a specific organ of the body and include common diseases such as type I diabetes, multiple sclerosis, psoriasis, and irritable bowel syndrome. Type I diabetes and multiple sclerosis are induced by destruction of insulin-secreting pancreatic cells and neuronal cell damage in the brain and spinal cord by T cells, respectively. Psoriasis is a skin condition that manifests redness and irritation as well as thick, flaky patches due to inflammation of the skin, whereas irritable bowel syndrome patients suffer from inflammation of the small intestine and colon. The various organ specific autoimmune diseases often occur together in many combinations. In systemic autoimmune diseases that affect multiple tissues and organs of the body, autoantibodies and autoreactive T cells recognize autoantigens that are ubiquitously present in our body. Examples include rheumatoid arthritis caused by inflammation of joints and surrounding tissues and systemic lupus erythematosus, which affects the skin, joints, kidneys, brain, and other organs
Although individual autoimmune diseases are not very common, they collectively affect more than 5% of the population and their incidence is rising. In the USA, it is estimated that up to 50 million people are suffering from autoimmune disorders. The disease incidence rate depends on age and sex. Roughly, 75 percent of those affected by autoimmune disease are women and, in some disorders such as systemic lupus erythematosus, females have up to 9 times higher a chance of getting the disease. Levels of female hormones such as estrogen and genes on the X-chromosome have been shown to contribute to the sex bias. Autoimmune diseases often run in families, suggesting the important role of genetic background. However, a single gene mutation rarely explains the development of the autoimmune diseases. Rather, multiple genes collectively contribute to the susceptibility of individual diseases. Other factors that affect autoimmune disorders are mental or physical stress, diet, infection, and environmental factors such as pollutants and pesticides.
Autoimmune diseases are not transmissible to other people except for some autoantibody-mediated disorders.  In such diseases, transmission of autoantibodies across the placenta during pregnancy can lead to disease in the fetus or newborn babies. The symptoms of the disease in the infants usually disappear rapidly as the maternal autoantibodies become degraded, however in some cases the autoantibodies can cause severe organ damage before they are removed. If such a case is predicted, speeding up the autoantibody clearance by exchange of the infant’s blood is recommended.
Most autoimmune diseases are chronic and symptoms usually fluctuate between periods of remission (little/no symptoms) and flare-ups (worsening symptoms). Currently, there are no cures or prevention for autoimmune diseases. So, treatment mainly focuses on relieving the symptoms and relies on drugs promoting general immune suppression such as steroids and NSAIDs, non-steroidal anti-inflammatory drugs. It is not still clear what causes the failure of natural self-tolerance mechanisms of our immune system and triggers autoimmune diseases. However, thanks to the recent advances in understanding the cellular and molecular mechanisms of various autoimmune diseases, new therapeutic options have become available. They include biologic drugs such as monoclonal antibodies against TNF-α, a small protein secreted by immune cells and cause inflammation. Currently, 3 out of the top 10 best-selling drugs target TNF-α for the treatment of rheumatoid arthritis and irritable bowel syndromes. The gross sale of the three drugs totaled 15 billion dollars last year in the USA alone, implying that development of novel and efficacious drugs for autoimmune diseases can not only help patients but also create enormous wealth.
In POSTECH, immunologists strive to solve the mysteries of autoimmune diseases and to find new therapies. POSTECH hosts the Academy of Immunology and Microbiology, the only Institute for Basic Science center in the nation focusing on immunology. POSTECH also boasts the only germ-free animal facility in Korea, which houses laboratory mice that have no commensal bacteria living in or on them. The impact of commensal microbiota on the host immune system is one of the hottest research fields at the moment, and the relationship between commensal microbes and autoimmune diseases is certainly a promising avenue of study.