Complement system

Complement is a type of protein in human and vertebrate serum and tissue fluid that is activated and has biological activity and can mediate immune and inflammatory reactions. Soluble proteins, regulatory proteins and related membrane proteins (receptors) and other complement proteins together form a multi-molecular system, so it is also called the complement system. According to different functions, the components of the complement system can be divided into three categories: first, inherent components: including C1 ~ C9. B, D, P factors, mannose-binding lectin (MBL), serine protease, etc.; second, regulatory molecules: including soluble regulatory molecules and membrane binding regulatory molecules; third, receptor components: including ClqR, CRI, CR2, CR3, C3aR, CSaR and so on. Most complement components have biological functions only after activation. After the intrinsic components of complement are activated sequentially, active enzymes can be formed. Eventually the cytolytic effect is mediated in the form of a membrane attack complex (MAC). As an important part of the body's immune regulation, the complement system is a bridge connecting innate immunity (non-specific immunity) and adaptive immunity (specific immunity). It is involved in the process of anti-infection, regulation of inflammatory response, treatment of self-antigens, regulation of immune gene expression and so on. At the same time, it plays an important role in the regulation of immune homeostasis such as immunoregulation and autophagy regulation.

Complement system and autoimmune diseases

Autoimmune disease (AID) is a type of disease caused by the immune response disorder that causes the immune system to attack self-antigens. As an important component of the immune system, complement is closely related to the pathogenesis of AID. At present, it is believed that complement defects or abnormal functions are one of the main causes of AID.

3.1 Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a typical autoimmune inflammatory connective tissue disease involving multiple organs. It is related to the binding of autoantibodies to tissues and organs such as the chorion, joints, nerves, skin, and kidneys. The mechanism of complement in the pathogenesis of SLE is still unclear. On the one hand, complement in SLE patients is strongly activated and consumed, so patients often have hypocomplementemia; on the other hand, complement defects also participate in the pathogenesis of SLE. It is currently believed that the immune complex formed by self-antigens and antibodies is the main pathogenic mechanism of SLE. In patients with SLE, a large amount of Clq and C4 are consumed, and the density of the complement receptor CR1 (CD35) on the surface of red blood cells decreases, resulting in an increase in the number of immune complexes, which are further accumulated in target organs and tissues. At the same time, the defect of apoptotic cell clearance mechanism is also closely related to the pathogenesis of SLE.

3.2 Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Patients may present with swelling, pain, and even joint mobility and deformity in multiple joints throughout the body, which is manifested as joint synovitis, which eventually causes bone and cartilage erosion. Human complement is mainly synthesized by the liver. In the acute inflammatory reaction period, the synovial tissue in the joint can also produce complement. A large number of studies have shown that complement activation is involved in the pathogenesis of RA. The study found that the complement protein in the synovial fluid of RA patients increased significantly, but due to the excessive consumption of complement components, the overall performance was a decrease in complement levels. At the same time, the complement activity in the patient's joint fluid s significantly lower than that of patients with non-inflammatory arthritis. Soluble complement activation fragments significantly increase the increase of C5a and C3a in serum and synovial fluid, which may be related to severe infection. In infected and hyperplastic synovial tissues, C5aR expression was up-regulated and soluble MAC (membrane attack complex) increased.

To be continued in Part II…

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