Complement deficiency

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Complement deficiency
Complement pathway.svg
Complement pathway (normal)
Classification and external resources
Specialty hematology
ICD-10 D84.1
ICD-9-CM 279.8
OMIM 217000 120820, 120900, 610102
DiseasesDB

1847 1869 , 1873 , 7384

, 34381
eMedicine med/419 ped/447

Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins.[1] Because there are redundancies in the immune system, many complement disorders are never diagnosed, some studies estimated that less than 10% are identified.[2]Hypocomplementemia may be used more generally to refer to decreased complement levels[3] while secondary complement disorder is to low complement levels that are not directly due to a genetic cause but secondary to another medical condition.[4]

Types[edit]

  • Disorders of the proteins that act to inhibit the complement system (such as C1-inhibitor) can lead to an overactive response, causing conditions such as hereditary angioedema[5]
  • Disorders of the proteins that act to activate the complement system (such as C3) can lead to an underactive response, causing greater susceptibility to infections.[6]

Signs/symptoms[edit]

The following symptoms (signs) are consistent with complement deficiency in general:[7][8][9]

Causes[edit]

The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are autosomal recessive, while properdin deficiency could be X-linked inheritance, and finally MBL deficiency can be both [10]

Complications[edit]

Neisseria, a possible complication

Vaccinations for encapsulated organisms is crucial for preventing infections in complement deficiencies.[medical citation needed] Among the possible complications are the following:

Mechanism[edit]

C4 role in Schizophrenia

The mechanism of complement deficiency consists of:

  • C2 -in regards to complement component 2 deficiency, about 5 different mutations in the C2 gene are responsible for it.In turn immune function decreases and infection opportunities rise. One of the most common mutations deletes 28 DNA nucleotides from C2 gene. Therefore no C2 protein is made which would help make convertase C3. Ultimately this delays/decreases immune response.[16]
  • C3 -in terms of complement deficiency in C3 it has been found that 17 mutations in C3 gene cause problems with complement component 3. This rare condition's mutations creates prevent cells, consequently the immune system ability to protect decreases.[17]
  • C4 -C4 deficiency has a very high percent association with systemic lupus erythematosus [18] C4 role in Alzheimer's disease is from Kolev et al, brain inflammation may have a role in Alzheimer's disease pathogenesis.Aβ42 can cause activation of C4,whats more Aβ can activate C4 in plasma (deficient of C1q)[19] A recent study indicates that a variation of C4 has a role in schizophrenia.[20]

Diagnosis[edit]

Complement tests
C4 (C) FB (A) C3 CH50 Conditions
 · PSG, C3 NeF AA
 ·  · HA, C4D
 ·  ·  · TCPD
 · /↓ SLE
inflammation

Among the diagnostic tests that can be done in determining if an individual has complement deficiencies is:[7][18]

Treatment[edit]

In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).[7][10]

Pneumococcus and haemophilus infections prevention can be taken via immunization for those with complement deficiency.[10] Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.[4]

Epidemiology[edit]

In terms of the epidemiology of complement deficiency one finds that C2 deficiency for example, is prevalent in 120,000 people in Western countries,[10] it occurs in about 1 in 10,000 persons.[21]

See also[edit]

References[edit]

  1. ^ Winkelstein, Jerry A. (2004). "The Complement System". In Gorbach, Sherwood L.; Bartlett, John G.; Blacklow, Neil R. Infectious Diseases. Lippincott Williams & Wilkins. pp. 8–13. ISBN 978-0-7817-3371-7. 
  2. ^ Sjöholm, A.G.; Jönsson, G.; Braconier, J.H.; Sturfelt, G.; Truedsson, L. (2006). "Complement deficiency and disease: An update". Molecular Immunology. 43 (1–2): 78–85. doi:10.1016/j.molimm.2005.06.025. PMID 16026838.  – via ScienceDirect (Subscription may be required or content may be available in libraries.)
  3. ^ (ed.), Larry W. Moreland (2004). Rheumatology and immunology therapy : a to Z essentials ([1st ed.]. ed.). Berlin: Springer. p. 425. ISBN 9783540206255. Retrieved 30 August 2016. 
  4. ^ a b Complement-Related Disorders at eMedicine
  5. ^ Davis, Alvin E.; Mejia, Pedro; Lu, Fengxin (1 October 2008). "BIOLOGICAL ACTIVITIES OF C1 INHIBITOR". Molecular immunology. 45 (16): 4057–4063. doi:10.1016/j.molimm.2008.06.028. ISSN 0161-5890. PMC 2626406Freely accessible. PMID 18674818. 
  6. ^ Ram, S.; Lewis, L. A.; Rice, P. A. (7 October 2010). "Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy". Clinical Microbiology Reviews. 23 (4): 740–780. doi:10.1128/CMR.00048-09. ISSN 0893-8512. PMC 2952982Freely accessible. PMID 20930072. 
  7. ^ a b c "Complement Deficiency Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Medscape. Retrieved 21 September 2016. 
  8. ^ Barone, [edited by] Michael Crocetti, Michael A.; Barone, Michael A.; Oski, Frank A. (2004). Oski's Essential pediatrics (2. ed.). Philadelphia: Lippincott Williams & Wilkins. p. 670. ISBN 9780781737708. Retrieved 21 September 2016. 
  9. ^ Pettigrew, H. David; Teuber, Suzanne S.; Gershwin, M. Eric (September 2009). "Clinical Significance of Complement Deficiencies". Annals of the New York Academy of Sciences. 1173 (1): 108–123. doi:10.1111/j.1749-6632.2009.04633.x. ISSN 1749-6632. Retrieved 21 September 2016. 
  10. ^ a b c d e http://patient.info/doctor/complement-deficiencies Patient.info
  11. ^ editors, Asghar Aghamohammadi, Nima Rezaei,; Rezaei, Nima (2012). Clinical cases in primary immunodeficiency diseases a problem-solving approach. Berlin: Springer. p. 334. ISBN 9783642317859. Retrieved 21 September 2016. 
  12. ^ "OMIM Entry - # 312060 - PROPERDIN DEFICIENCY, X-LINKED; CFPD". omim.org. Retrieved 21 September 2016. 
  13. ^ Gower, Richard G; Busse, Paula J; Aygören-Pürsün, Emel; Barakat, Amin J; Caballero, Teresa; Davis-Lorton, Mark; Farkas, Henriette; Hurewitz, David S; Jacobs, Joshua S; Johnston, Douglas T; Lumry, William; Maurer, Marcus (15 February 2011). "Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies". The World Allergy Organization Journal. 4 (Suppl 2): S9–S21. doi:10.1097/1939-4551-4-S2-S9. ISSN 1939-4551. PMC 3666183Freely accessible. PMID 23283143. 
  14. ^ "Systemic Lupus Erythematosus. Lupus treatment; information | Patient". Patient. Retrieved 21 September 2016. 
  15. ^ "Membranoproliferative Glomerulonephritis: Background, Pathophysiology, Etiology". Medscape. Retrieved 21 September 2016. 
  16. ^ Reference, Genetics Home. "C2 gene". Genetics Home Reference. Retrieved 21 September 2016. 
  17. ^ Reference, Genetics Home. "C3 gene". Genetics Home Reference. Retrieved 21 September 2016. 
  18. ^ a b "Complement Deficiencies Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 21 September 2016. 
  19. ^ Kolev, Martin V; Ruseva, Marieta M; Harris, Claire L; Morgan, B. Paul; Donev, Rossen M (1 March 2009). "Implication of Complement System and its Regulators in Alzheimer’s Disease". Current Neuropharmacology. 7 (1): 1–8. doi:10.2174/157015909787602805. ISSN 1570-159X. PMC 2724661Freely accessible. PMID 19721814. 
  20. ^ http://www.medscape.com/viewarticle/858062
  21. ^ http://www.omim.org/entry/217000

Further reading[edit]