Complement deficiencies

What is a complement deficiency?

Complement is a group of more than 30 proteins found in blood and tissues throughout the body. They play an important role in immune system function by enhancing the inflammatory response and pathogen elimination. A deficiency in any one of these complement proteins can cause a wide range of symptoms, stemming from:

• Ineffective opsonisation
• Lytic activity defects

Complement deficiencies are considered to be rare disorders and compromise between 1–10% of all cases of primary immunodeficiency. Complement deficiency is also known as hypocomplementaemia.

What causes a complement deficiency?

Complement deficiencies are inherited. Most are autosomal recessive traits with the exception of a deficiency of the C1 inhibitor, which is autosomal dominant, and properdin deficiency, which is X-linked.

What are the results of a complement protein deficiency?

Complement deficiencies affect various organs.

• Recurrent infections. Depending on the kind of complement deficiency, patients can present with viral infections including herpes simplex and influenza A, as well as pneumonia, ear infections, colds, meningococcal disease and sepsis.
• Autoimmune diseases. The most common autoimmune disease associated with this disorder is systemic lupus erythematosus.
• Renal diseases. These can include glomerulonephritis and atypical haemolytic uraemic syndrome.
• Angioedema
• Vasculitis
• Age-related macular degeneration
• Antiphospholipid-antibody syndrome (APS)
• Paroxysmal nocturnal haemoglobinuria

What are the risk factors for complement deficiencies?

The risk factors for complement deficiencies include:

• Family history
• Race. Caucasians are at greater risk for properdin and C2 deficiencies, while those of African descent are at greater risk for C6 deficiencies and those of Asian descent for C8 and C9 deficiencies.
• Age. Some forms of complement deficiency will present within the first months to first years of life; others will present in later childhood or adolescence.
• Sex. Most complement deficiencies affect both sexes equally, but properdin deficiency, for instance, is X-linked and presents only in males.

How is a complement deficiency diagnosed?

Complement deficiencies are commonly diagnosed with the following tests:

• Total serum class haemolytic complement (CH-50) test
• Alternative haemolytic complement (AP-50) test
• Screening for immune complex diseases
• Antinuclear serology to test for lupus
• Urinalysis
• Complete blood count (CBC)

How is a complement deficiency treated?

There are no specific treatments available as yet for complement deficiencies.

Treatment can include:

• Prevention and treatment of infections (including the use of antibiotics)
• Use of fresh, frozen plasma to bolster immunity
• Immunisation against Neisseria meningitidis for boys with properdin deficiency
• Immunosuppressive therapy