Scientists discover the inflammatory disease of their own and deeply analyze the cause of the disease

February 25, 2020 / BIOON / -- more than 20 years ago, three generations of American families were transferred to the National Institutes of health for treatment due to an unknown disease Their age was 10-82 years old, and their symptoms included unexplained high fever (up to 41 times per month), which lasted for 2-7 days They also present with painful lymphadenopathy, splenomegaly and hepatomegaly, abdominal pain, mouth ulcers, joint pain and other symptoms These symptoms appeared shortly after they were born, which seemed like an inflammatory reaction However, clinicians could not trace these symptoms back to the infection Now researchers have found that the disease symptoms of these patients are typical of their own inflammatory diseases, and patients will have fever and inflammation for no reason Due to the regular occurrence of inflammation in patients, these diseases are also known as "periodic fever syndrome" In addition to pain and weakness, some diseases will damage important organs, such as the heart and lungs Photo source: Fars news agency what causes self inflammatory diseases? Autoimmune diseases are usually caused by the abnormal activation of innate immune system, which is the first defense line for the body to resist pathogen invasion; innate immune system is a natural response, which can quickly attack against foreign invaders, and its multiple functions are to release cytokines These immune messengers alert the body and recruit other cells to participate Fighting, increasing blood circulation and causing fever are essential However, in autoimmune diseases, invasive microorganisms do not cause fever and inflammatory symptoms On the contrary, genetic changes (gene mutations) can cause the innate immune system to be activated, leading to uncontrollable inflammation, which seems to have no reason Autoinflammation usually starts in childhood, usually from the birth of an individual and lasts for a lifetime; this genetic mutation can be passed from parents to children, resulting in multiple cases in a family Different from autoimmune diseases, such as multiple sclerosis, the latter is caused by the defect of adaptive immune system (another branch of immune response); at present, there are many different autoimmune diseases, usually caused by different inherited mutations How to treat inflammatory disease? Autoinflammatory diseases cannot be cured The treatment can usually relieve the symptoms of the disease when the patient has a disease attack, and the patient will often use large doses of corticosteroids, which is a wide range of methods, which can be used to inhibit the function of the host immune system Self inflammatory diseases are also rare, which makes it difficult for scientists to develop effective therapies for travel Since autoimmune diseases are usually associated with the production of excess cytokines, researchers sometimes use so-called biological antibodies to remove these excess cytokines, including some tumor necrosis factor (TNF) or interleukin-1 However, biological agents are very expensive, which can also produce obvious side effects; in the case of patients do not know the cause of inflammatory diseases, the treatment of patients is a process of repeated trials, and drugs that are effective for one person may not be effective for another person Is genetic testing helpful? Looking for gene mutations that cause autoimmune diseases may help researchers develop new genetic diagnosis techniques However, some people with autoimmune diseases may not have changes in some known pathogenic genes Therefore, researchers want to start to look for other genetic causes of autoimmune diseases Photo source: pasmov.com how do we find out the underlying mechanism? When NIH researchers were trying to find out the cause of the above-mentioned family diseases in the United States, another theory emerged in Australia Later, researchers focused on the role of TNF, a major cytokine, which can control many aspects of the body's inflammatory response, and the function of its partner ripk1; generally, the body has many checks and balances mechanisms to ensure these molecules Under strict control The researchers then identified a key mutation in the gene that encodes ripk1, which causes an amino acid change, but that's enough to make its partner TNF an "elite killer"; this may be the reason why inflammatory diseases can't be effectively controlled behind the family diseases in the United States The researchers named this disease CRIA syndrome, or ripk, which is not easy to split 1 The induced CRIA syndrome (cleavage resistant ripk1 induced autoinflammatory syndrome) What does this mean? Understanding the molecular mechanism behind CRIA's promotion of inflammation may help researchers to further clarify the underlying causes of disease and develop effective treatment methods In this case of American families, the use of factors that inhibit wrong ripk1 as a treatment may be an effective choice Today, the discovery of CRIA syndrome confirms that ripk1 may play a key role in the regulation of human body inflammation, so it may also play a role in more common human diseases, such as colitis, rheumatoid arthritis and cattle hide fresh Reference materials: [1] what to know about tumor nexus factor [2] silk, J., Rickard, J & gerlic, M the wide role of rip kings in Nigeria and information NAT Immunol 16689 – 697 (2015) Doi: 10.1038/ni.3206 [3] autoinflammatory disease: the ray immune condition with waves of never by John silk and Najoua Lalaoui， The Conversation