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Acquired deficiencies 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


Deficiencies in complement proteins may be inherited or acquired (secondary). Secondary causes of complement deficiency will be presented in this topic review. Inherited disorders of the complement system, as well as a description of the complement pathways and the clinical evaluation of complement, are presented separately. (See "Inherited disorders of the complement system" and "Complement pathways" and "Overview and clinical assessment of the complement system".)


Acquired deficiencies in complement proteins are more common than inherited complement disorders. Reductions in complement secondary to acquired disease processes are usually only partial and affect several complement components at once. As an example, approximately 50 percent of patients with systemic lupus erythematosus (SLE) will have reductions in C4 and C3, reflecting classical pathway activation.

These acquired complement deficiencies are most commonly encountered in diseases featuring autoantibodies. In many diseases, such as milder forms of SLE, augmented hepatic synthesis of components may be sufficient to maintain the levels in the normal range. The management of most disorders of the complement system featuring excessive activation focuses on the treatment of the underlying disorders.

Challenges in interpretation — One problem clinicians may encounter when managing disorders featuring acquired deficiencies of complement components is that the predisease levels of proteins, such as C3, are rarely known. For example, the "normal" laboratory range of C3 in the population is from 80 to 160 mg/dL. A 17-year-old female with new-onset SLE may present with a C3 value of 92 mg/dL. Although this is considered in the "normal range," if her post-treatment C3 value rises to 125 mg/dL in six weeks, then her predisease value was at least this or higher. Even at 125 mg/dL, a C3 turnover study or assessment of complement split products might show mildly accelerated consumption. Measuring C4, which commonly parallels changes in C3 levels, is more complicated because of C4 copy number, which is discussed elsewhere. Thus, complement levels need to be interpreted in the context of the clinical setting. (See "Inherited disorders of the complement system", section on 'C4 deficiency'.)


Acquired deficiencies in complement proteins may result from several mechanisms:

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Literature review current through: Nov 2017. | This topic last updated: Oct 05, 2017.
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