多发性硬化症,免疫性疾病 z-bo 2020-10-29 377

　　About half of multiple sclerosis patients carry HLA-DR15 gene mutations. Recently, a research report entitled "HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis" was published in the international journal Cell In the study, scientists from the University of Zurich and other institutions have revealed how this genetic susceptibility (HLA-DR15 gene mutation) can be combined with environmental factors to promote the occurrence of patients’ autoimmune diseases—multiple sclerosis, the researchers said , The decisive factor is the formation of a series of immune cells, although these cells can effectively resist pathogens such as Epstein-Barr virus that attack brain tissue.

　　Multiple sclerosis is an autoimmune disease that damages the brain and spinal cord tissue of the body, and also severely affects the quality of life of patients. It affects the health of approximately 2.5 million people worldwide, most of which are young people. The cause of multiple sclerosis is a complex interaction between genetic factors and environmental factors such as smoking or infection. In nearly 50 years, researchers have discovered that a mutation in a gene called HLA-DR15 is closely related to the occurrence of multiple sclerosis (MS). This gene mutation is mainly related to up to 60% of the risk of disease. If the gene Carriers (approximately a quarter of healthy people carry the HLA-DR15 gene) are also infected with the Epstein-Barr virus, and they will develop a disease called Pfeiffer (also known as glandular fever or infectious mononucleosis) The risk of multiple sclerosis will increase 15 times.

　　Researcher Professor Roland Martin said that there is currently definite evidence that the interaction between HLA-DR15 and infectious factors such as Epstein-Barr virus is of great significance in promoting the occurrence of multiple sclerosis, but until now, researchers have still not The specific molecular mechanism behind it is not clear. In this study, the researchers found through research that the immune cells of HLA-DR15 gene carriers can effectively recognize specific pathogens such as Epstein-Barr virus, but this "adaptability" may induce an immune response that attacks the patient's own brain tissue.

　　The product of the HLA-DR15 gene can control how the adaptive immune system shapes the components of the immune catalog, thereby promoting the body to effectively recognize and attack pathogens. One of the sites of the HLA-DR15 molecule is on the surface of white blood cells. When located on the surface of white blood cells, It can present protein fragments from bacteria, viruses and body cells to T lymphocytes in immune cells. Then the T lymphocytes that can control the body’s immune response can learn to recognize foreign proteins and the body’s own tissues. This training of immune cells first occurs in the thymus and secondly in the blood. Because of the possibility of pathogens being more likely than T lymphocytes Much more, so each T lymphocyte must respond to many different antigens and pathogens.

　　In this study, the researchers first investigated which HLA-DR15 fragments would be captured and presented to immune cells. To this end, they used two new types of antibodies that can identify patients with multiple sclerosis with a high level of specificity Two HLA-DR15 mutations occurred in the body, and it was found that the HLA-DR15 molecule in the thymus mainly presents its own fragments, which researchers did not know before. The T lymphocytes trained in this way will then migrate to the body’s blood. If the HLA-DR15 mutation carrier is infected with the Epstein-Barr virus, the T lymphocytes can recognize the Epstein-Barr virus fragment in the blood, compared to the HLA-DR15 fragment In other words, the virus fragment has a stronger activation effect. Therefore, T lymphocytes can not only control the cells infected by the virus, but also migrate to the brain and interact with the patient's own proteins, inducing the patient's autoimmune response. Nearly 100% of patients with multiple sclerosis will be infected by Epstein-Barr virus, which is the biggest environmental factor that induces multiple sclerosis. Researchers also found that in patients with multiple sclerosis, the intestinal flora Akkermansia muciniphila fragments The reaction level will increase abnormally.

　　Researcher Martin concluded that the most important genetic risk factor for multiple sclerosis may shape the catalog of T lymphocytes, so that they can respond better to specific infectious factors such as Epstein-Barr virus and intestinal flora. However, as the experimental results show, this type of T lymphocytes also react to proteins found in the brain through a cross-reaction method. Therefore, the disadvantage of this immune adaptation is that the affected population may be The immune response to attack one's own brain tissue becomes susceptible, which increases the risk of multiple sclerosis. The results of this article clarify for the first time how the combination of genetic susceptibility and specific environmental factors can induce people to develop autoimmune diseases. In addition, the researchers also revealed that the tracking mechanism may play a key role in the occurrence of many other autoimmune diseases. In addition to improving researchers' understanding of the causes behind the disease, relevant research results are also expected to help scientists develop new therapies for the treatment of autoimmune diseases such as multiple sclerosis.