Patient Education
What is complement?
Complements are a group of proteins in the blood that help to fight infection. The complement system includes at least 30 proteins of which the common ones are C1, C2, C3, C4, C5, C6, C7, C8, C9, Factor B, Factor D & C1 inhibitor.
How do complements fight infections?
Each complement protein has a different role to fight infection, but they act in a cascade, one protein activating the next like a domino effect. These complements are activated either by the interaction of antibodies with the germs (classical) or by binding of mannose-binding lectin to the sugars on the bacterial surface (lectin pathway) or by another pathway (alternative pathway). C3 coats the bacteria so that they can be easily killed by the neutrophils. C5 to C9 punch holes in the bacteria causing them to rupture and die. C3 and C5 increase blood supply at the site of infection and thus increase the number of neutrophils at the infection site. C1 inhibitor helps to regulate the complement cascade and prevents it from activating uncontrollably.
What are complement deficiencies?
Deficiency in any protein of the complement system can lead to recurrent infections. Complement deficiencies are part of primary immunodeficiencies. Common complement deficiencies are deficiency of C3, deficiency of C2, deficiency of C5, and deficiency of C1 inhibitor.
What are the symptoms of complement deficiencies?
Patients with C3 deficiencies are prone to get recurrent bacterial infections. They are also more prone to get autoimmune diseases such as systemic lupus erythematosus (SLE) or juvenile rheumatoid arthritis. Patients with a deficiency of C5, C6, C7, C8, or C9 are prone to infection by a particular bacterium? Neisseria meningitides (it causes meningitis). Patients with a deficiency of C1 inhibitor are prone to get hereditary angioedema. (Hereditary angioedema is a condition that causes swelling of skin or in the airways leading to breathing problems).
How is the diagnosis of complement deficiency made?
CH50 is the commonest test done to check the integrity of complement cascade. Testing of individual components (their quantity and their ability to function properly) is done in special laboratories. CH50 is absent in defect in one complement component. The function of the complement can be tested by the AP50 test.
Do complement deficiencies run in families?
Most complement deficiencies occur due to defects in both copies of a gene (autosomal recessive). Thus parents are usually unaffected but each-one has one defective gene. Only if the child gets both defective genes, then he/she will get the disease. Thus the chance of a child being affected where both parents have a defective gene is 25%.
In the case of properdin deficiency, since the genetic defect is present on the x-chromosome, it affects only the boys. C1 inhibitor deficiency requires only one copy of the gene to be abnormal (autosomal dominant). Thus a child of a parent who has hereditary angioedema has a 50% chance of getting the disease.
What is the treatment of complement deficiency?
Treatment of infections promptly and immunization with meningococcal vaccine (in patients with C5-C9 deficiency) is useful. Androgens such as danazol or oxandrolone can be useful to treat patients with hereditary angioedema. C1 inhibitor can also be administered to terminate an attack.
1. Dunkelberger, J.R, Song, WC, 2010 Complement and its role in innate and adaptive immune responses. Cell. Res 20, 34-50.
2. JE Figueroa, Densen ,Infectious diseases associated with complement deficiencies. Clin Microbiol Rev. 1991 Jul; 4(3): 359–395.
3. Hirsch RL, Griffin DE, Winkelstein JA Host modification of Sindbis virus sialic acid content influences alternative complement pathway activation and virus clearance. J Immunol. 1981 Nov;127(5):1740-3.
4. Saifuddin et al. Interaction of MBL with primary isolates of HIV 1. J.gen Viro,81, 949-955, 2000.
5. Grumach .Are complement deficiency really rare. overview on prevalence, importance and modern approach. Molecular Immunology 2014.
6. Angela R. Bryan & Eveline Y. Wu Complement Deficiencies in Systemic Lupus Erythematosus. Curr Allergy Asthma Rep (2014) 14:448.
7. Skattum et al, 2011.Complement deficiency states and associated infections, Mol Immuno 48, 1643-1655.
8. Fijen CA et al,1999. Properdin Deficiency: molecular basis and disease association. Mol. Immunology 36; 863-867.
9. Schejbel et al 2009 Properdin Deficiency in recurrent otitis media and pneumonia. Clin Immnu 131:456-463.
10. Fukumori et al 1989, A high incidence in C9 deficiency among healthy blood donors in Japan. Immuno 1:85-89.
11. Nagata et al 1989, Inherited deficiency of ninth component of complement: an increased risk of meningococcal meningitis. J ped 114,260-264.
12. Stengaard-Pedersen 2003. Inherited deficiency of MBL associated serine protease 2. N Eng J Med 349, 554-560.
13. Munthe-Fog et al 2009. Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency. New Engl J.Med 360:2637-2644.
14. Truedsson et al 2007. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 40.560-566.
15. Sjoholm et al 2006. Complement deficiencies and diseases; an update. Mol. Immunol 129, 123-131.
16. Jonsson et al 2007. Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency. Rheumatology ( Oxford)46,1133-1139.