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Inherited disorders of the complement system

M Kathryn Liszewski, PhD
John P Atkinson, MD
Section Editors
Jordan S Orange, MD, PhD
Peter H Schur, MD
Deputy Editor
Anna M Feldweg, MD


Inherited deficiencies of complement components are rare disorders that predispose to bacterial infections and/or systemic lupus erythematosus (SLE). They are associated with predictable defects in complement-dependent function, as the affected individual loses not only the activity of the deficient protein, but also the functions of the proteins that follow in the cascade.

Inherited complement deficiencies are classified into two general categories: 1) integral component defects and 2) regulatory component defects [1]. Inherited disorders of the complement system will be reviewed here. Acquired disorders and the general evaluation of the complement system are discussed separately. (See "Acquired deficiencies of the complement system" and "Overview and clinical assessment of the complement system" and "Complement pathways".)


Deficiencies in an integral component of the activating cascades — Inherited disorders of complement components present predominantly with recurrent bacterial infections and/or systemic lupus erythematosus (SLE) [2-4].

Infections – Patients with deficiency of a complement pathway protein are susceptible to recurrent sinopulmonary bacterial infections, bacteremia, and/or meningitis. The pathogens most commonly implicated are encapsulated bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis. (See "Approach to the child with recurrent infections" and "Approach to the adult with recurrent infections".)

Autoimmunity – The most common autoimmune disorder by far among patients with a total complement deficiency is SLE [5-17]. SLE commonly develops in individuals deficient in an early component of the classical pathway (ie, C1q, C1r, C1s, C4, and C2). (See "Systemic lupus erythematosus (SLE) in children: Clinical manifestations and diagnosis" and "Overview of the clinical manifestations of systemic lupus erythematosus in adults".)

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Literature review current through: Sep 2017. | This topic last updated: Aug 29, 2017.
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