[Clinical aspects of the complement system].

Abstract

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.

• Authors: Hiroshi Tsukamoto, Takahiko Horiuchi
• Journal: Rinsho byori. The Japanese journal of clinical pathology (Rinsho Byori) Vol. 54 Issue 7 Pg. 757-62 (Jul 2006) ISSN: 0047-1860 [Print] Japan
• PMID: 16913667 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• FCN3 protein, human
• Glycoproteins
• Lectins
• Complement System Proteins

Topics

• Animals
• Complement Pathway, Mannose-Binding Lectin (immunology)
• Complement System Proteins (deficiency, immunology)
• Glycoproteins
• Hemolytic-Uremic Syndrome (immunology)
• Humans
• Lectins
• Lupus Erythematosus, Systemic (immunology)