Multiple sclerosis genetics

Many people in life have some genetic diseases. Because these genetic diseases may develop into offspring, and then be transmitted to offspring's children, and then to each other, they have a great impact on the family and life. So when encountering multiple sclerosis, everyone will consider whether it is hereditary and the diagnosis of the disease.

Pathogenesis

1. Viral infection and autoimmune response The molecular mimicry theory believes that the virus that infects the patient may have common antigens with CNS myelin proteins or oligodendrocytes, that is, the viral amino acid sequence is identical or very similar to the amino acid sequence of a certain polypeptide of nerve myelin components such as MBP. It is speculated that after viral infection, T cells in the body are activated and produce antiviral antibodies, which can cross-react with nerve myelin polypeptide fragments, leading to demyelinating lesions.

Johnson proposed that the autoimmune response of the nervous system caused by viral infection is related to the abnormal expression of autoantigens by CNS cells. He discovered that several different viruses (measles, rubella, varicella) can induce an autoimmune response by T cells against alkaline myelin proteins. This means that the T cells recognize both the virus and recognizable structures on the myelin sheath. Once this autoimmune response is triggered by a virus in childhood, it can be reactivated by any common virus later, and this is more pronounced in higher latitudes. This molecular similarity (the virus shares the same antigens with CNS myelin or oligodendrocytes) is theoretically attractive for the pathogenesis of several diseases, such as rheumatic fever and Guillain-Barré syndrome.

The classic experiment that supports that MS is an autoimmune disease is to immunize Lewis rats with myelin antigens such as myelin basic protein (MBP), which can cause experimental autoimmune encephalomyelitis (EAE), an experimental animal model of MS. Moreover, the transfer of sensitized cell lines that recognize MBP polypeptide fragments from EAE rats into normal rats can also cause EAE, proving that MS is a T cell-mediated autoimmune disease.

The tissue damage and neurological symptoms of MS are thought to be caused by an immune response directed against myelin antigens. Viral infection or other stimuli can promote the entry of T cells and antibodies into the CNS by destroying the blood-brain barrier, leading to increased expression of cell adhesion molecules, matrix metalloproteinases and proinflammatory cytokines, which together attract other immune cells, decompose the extracellular matrix to facilitate the migration of immune cells and activate autoimmune responses to self-antigens, such as MBP, myelin-associated glycoprotein (MAG), oligodendrocyte glycoprotein (MOG) and lipid-containing protein (PLP), αB-crystallin (αB-crystallin), phosphodiesterase and S-100. These target antigens trigger autoimmune responses that may involve cytokines, macrophages, and complement by binding to antigen-presenting cells. In particular, helper T cell type 1 (Th1) cytokines such as IL-2 and IFN-γ may be associated with the onset of MS. Immune attack can cause demyelination, slowing nerve conduction and leading to neurological symptoms.