Complements and Their Role in Systemic Disorders

Abstract

The complement system is critical to the body's innate defense against exogenous pathogens and clearance of endogenous waste, comprising the classical, alternative, and lectin pathways. Although tightly regulated, various congenital and acquired diseases can perturb the complement system, resulting in specific complement deficiencies. Systemic rheumatic, neurological, ophthalmological, renal, and hematological disorders are some prototypical complement-mediated diseases. An adequate understanding of the mechanisms of the normal complement system and the pathophysiology of complement dysregulation is critical for providing diagnostic clues and appropriately managing these conditions. This review guides clinicians in understanding the role of complement factors in systemic diseases and what diagnostic and therapeutic options are available for complement-mediated disorders.

Keywords: acquired deficiency; complement; congenital deficiency; diagnosis; pathophysiology; systemic disease; therapeutics.

Figure 1. A schematic figure of the complement system regulation

Created by Muhammad M Javaid. C1Inh: C1 inhibitor; C4BP: C4b-binding protein; DAF: decay-accelerating factor; MCP: membrane cofactor protein; MBL: mannose-binding lectin; MASP: mannose-binding lectin-associated serine proteases. Regulators (inhibitors and inactivators) are shown in purple.