Q&A: Complement Deficiencies

The complement system is a major component of innate immunity and a "complement" (from which its name is derived) to antibody-triggered responses. It consists of nearly 60 plasma and membrane proteins that form three distinct but overlapping activating pathways, as well as a common terminal lytic cascade and a network of regulators and receptors.

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In this article:
Complement deficiencies
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

Complement deficiencies

Deficiencies in complement proteins may be inherited or acquired (secondary).

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.

MCQ exam: clinical scenario

A patient with recurrent infections with encapsulated bacteria is found to have a primary complement deficiency.

Which two primary complement deficiencies most commonly predispose to infection by encapsulated bacteria?

a) C1 and C2
b) C4 and C9
c) C3 and C5
d) C6 and C7
e) C8 and C9

MCQ exam: answer

The correct answer is C.
C3 and C5 deficiencies are the primary complement deficiencies implicated here.

MCQ exam: explanation

The complement system consists of a group of circulating proteins that have immunologic effects when they are activated. Complement activation serves first to opsonize pathogens for phagocytosis; second, to attract inflammatory cells; and third, to kill the pathogen by creating pores in its membrane. Because these functions are closely tied to the actions of antibodies, defects in the complement system result in recurrent infections with extracellular bacteria, including encapsulated bacteria.

Primary deficiencies of C3 or C5 predispose the host to infection by encapsulated bacteria . Deficiencies of the later complement components (i.e., C5b, C6, C7, C8, and C9) cause vulnerability principally to Neisseria gonorrhoeae and Neisseria meningitidis. Secondary (i.e., acquired) complement defects are seldom clinically important.

Reference(s)
1). UpToDate: Overview and clinical assessment of the complement system. Available online: https://www.uptodate.com/contents/overview-and-clinical-assessment-of-the-complement-system
2). UpToDate: Acquired deficiencies of the complement system. Available online: https://www.uptodate.com/contents/acquired-deficiencies-of-the-complement-system