What are complement deficiencies?

Updated: Apr 28, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Michael A Kaliner, MD  more...
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Answer

The complement system is part of the innate immune system. The complement system plays an important part in defense against pyogenic organisms. It promotes the inflammatory response, eliminates pathogens, and enhances the immune response. Deficiencies in the complement cascade can lead to overwhelming infection and sepsis.

In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). These findings underscore the duality of the complement system. It has a protective effect when functioning in moderation against pathogens; at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check.

Complement deficiencies are said to comprise between 1 and 10% of all primary immunodeficiencies. [1] The genetic deficiency of early components of the classical pathway (C1q, C1r/s, C2, C4) tend to be linked with autoimmune diseases [2] , whereas C5 to C9 may have enhanced susceptibility to meningococcal disease. Some new clinical entities are linked with partial complement defects.

Cases of complement deficiency have helped defined the role of complement in host defense. [4] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. Knowledge about the complement system is expanding. New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. This article outlines some of the disease states associated with complement deficiencies and their clinical implications. [5]

Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. [6] Genetic deficiency of C1q, C1r/s, C2, C4, and C3 is associated with autoimmune diseases, whereas deficiency of C5, C6, C7, C8, C9 increase susceptibility to infections.


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