Role In Disease – Aurin Biotech

The Complement System’s Role in Disease

Self-attack by the body’s own Complement system plays a role in a broad spectrum of diseases.

The Complement system works in every tissue of our body, providing an instant response to trauma and foreign invaders. However, if the severity of the response is not tightly regulated damage to healthy tissue can occur.

Once initiated, the proteins in the Complement cascade cannot discriminate between self and non-self or between healthy and damaged tissue. While Complement may not be the underlying causal factor in disease, its pathological activation or inadequate regulation is associated with tissue damage in many conditions.

Conditions associated with aberrant complement activation (along with selected references):

Adult respiratory distress syndrome (ARDS) (Robbins et al., 1987)
Age-related macular degeneration (AMD)
Allotransplantation (Pruitt and Bollinger, 1991)
Alzheimer’s disease (AD) (Rogers et al., 1992)
Arthus reaction (Szalai et al., 2000; Higgins et al., 1997)
Asthma (Regal et al., 1993)
Atherosclerosis
Atypical hemolytic uremic syndrome (aHUS)
Bullous pemphigoid (Liu et al., 1995)
Burn injuries (Gallinaro et al., 1992)
Crohn’s disease (Ahrenstedt et al., 1990)
Experimental allergic encephalomyelitis (EAE) (Davoust et al., 1999)
Experimental allergic neuritis (EAN) (Vriesendorp et al., 1995)
Forssman shock (Higgins et al., 1997)
Glomerulonephritis (Couser et al., 1985; Fujita et al., 1993; Iida et al. 1987; Quigg et al., 1998; Sheerin et al., 1997)
Haemolytic anemia (Schreiber and Frank, 1972)
Hemodialysis (Amadori et al., 1983)
Hereditary angioedema (Gadek et al., 1980)
Ischemia / reperfusion injuries (Kilgore et al., 1994; Weiser et al., 1996)
Immune complex-induced vasculitis (Cochrane, 1984)
Multiple sclerosis (Williams et al., 1994)
Multiple system organ failure (Heideman and Hugli, 1984)
Myasthenia gravis (Piddlesden et al., 1996)
Parkinson’s disease (PD)
Paroxysmal nocturnal hemoglobinuria (PNH)
Pick’s disease
Post-cardiopulmonary bypass inflammation (Pekna et al., 1993)
Psoriasis (Rosenberg et al., 1990)
Rheumatoid arthritis (Wang et al., 1995)
Septic shock (Hack et al., 1992)
Stroke (Huang et al., 1999)
Systemic lupus erythematosus (SLE) (Buyon et al., 1992)
Traumatic brain injury (TBI)
Vascular leak syndrome (Hack et al., 1994)
Xenotransplantation (Dalmasso, 1992)

Several excellent review articles have been published that discuss the complement system and its role in disease.

A. Sahu and J.D. Lambris. Complement inhibitors: a resurgent concept in anti-inflammatory therapeutics. Immunopharmacology 49 2000 133–148. (View PubMed Abstract, Access full-text PDF)
Daniel Ricklin and John D Lambris. Complement-targeted therapeutics. Nature Biotechnology 25 2007, 1265 – 1275. doi:10.1038/nbt1342. (View URL, Access full-text PDF)
Ehrnthaller C, Ignatius A, Gebhard F, Huber-Lang M. New insights of an old defense system: structure, function, and clinical relevance of the complement system. Mol Med. 2011 Mar-Apr;17(3-4):317–329. (View URL, Access full-text PDF)

References & Further Reading

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