[Clinical aspects of the complement system].
The complement system consists of more than 30 proteins and has 3 types of activation pathways: classical, lectin and alternative pathways. The complement system not only has a role in innate immunity but also works as an antibody-dependent effecter to eliminate pathogens. It is useful to measure serum levels of CH50, C3 and C4 in patients with immune-mediated diseases. While increased levels of CH50 are associated with non-specific inflammation, decreased levels of CH50 in combination with normal or decreased levels of C3 and C4 are associated with specific immune-mediated diseases. Recent studies have demonstrated that the defect in the clearance of immune complexes and apoptotic cells is associated with autoimmune disease. Mice deficient in Clq show a lupus-like phenotype with the appearance of antinuclear antibodies and glomerulonephritis due to a defect in the clearance of immune complexes and apoptotic cells. This at least explains the paradox that, in humans, deficiency in an early complement component is a major risk factor for SLE. It is demonstrated that mutations in factor H, membrane cofactor protein (MCP) and factor I gene are associated with atypical hemolytic uremic syndrome. Since the complement system is a central mediator of inflammation, it is recognized as a promising therapeutic target. Anti-C5 monoclonal antibody was developed to block the final stage of complement activation. Pexelizumab is a single chain, short-acting anti-C5 antibody and is used for reperfusion after myocardial infarction, or for coronary artery bypass graft surgery with cardiopulmonary bypass. Eculizumab is a long-acting anti-C5 antibody used for paroxysmal nocturnal hemoglobinuria, rheumatoid arthritis, membranous glomerulonephritis with promising results.
Tsukamoto
Hiroshi
H
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka.
Horiuchi
Takahiko
T
D000818:Animals; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency / Q000276:immunology*; D006023:Glycoproteins; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology; D006801:Humans; D037102:Lectins; D008180:Lupus Erythematosus, Systemic / Q000276:immunology
C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins; D003165:Complement System Proteins