Complement deficiencies

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Overview

Classification

Immunodeficiency Affecting Cellular and Humoral Immunity

Combined Immunodeficiency

Predominantly Antibody Deficiency

Diseases of Immune Dysregulation

Congenital Defects of Phagocytes

Defects in Intrinsic and Innate Immunity

Auto-inflammatory Disorders

Complement Deficiencies

Phenocopies of Primary Immunodeficiency

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[2], Anmol Pitliya, M.B.B.S. M.D.[3]

Overview

The complement system is a biochemical cascade which helps clear pathogens from an organism. It belongs to the innate immune system. Complement deficiencies can be inherited or acquired (as a result of complement-consuming disease state). Complement deficiency states may predispose affected individuals to angioedema, collagen vascular disease, or infection due to encapsulated organisms, especially Neisseria meningitidis.[1]

Classification

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complement Deficiencies
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Susceptibility to Infections
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIGH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LOW
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disseminated Nisserial Infections
 
 
 
 
 
Recurrent Pyogenic Infections
 
 
 
 
 
 
SLE like syndrome
 
 
 
Atypical hemolytic uremic syndrome
 
 
Others
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Absent CH50 & AH50 hemolytic activity, defective bacterial activity
 
 
 
Normal CH50, Absent AH50 hemolytic activity
 
 
 
 
 
C3LOF,C3,AR
 
 
 
 
 
 
 
C1q def: C1QA, C1QB, C1QC
 
 
 
 
C3GOF, C3, AD
 
 
 
C1 inhibitor SERPING1, AD
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C5 def:,C5
 
 
 
 
Properdin def:, PFC, XL
 
 
 
MASP2 def:, MASP2, AR
 
 
 
 
 
 
 
C1r def:
 
 
 
 
FactorB, GOF, CFB, AD
 
 
 
Membrane attack complex inhibitor def:, CD59
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C6 def:, C6
 
 
 
 
Factor D def:, CFD, AR
 
 
 
Fincolin3 def:, FCN3, AR
 
 
 
 
 
 
 
C1s def:
 
 
 
 
Factor H def:, CFH, AD or AR
 
 
 
CD55 def:, (CHAPLE disease), AR
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C7 def:, C7+vasculitis
 
 
 
 
 
 
 
 
 
Factor B, CFB, LOF, AR
 
 
 
 
 
 
 
C2 def:
 
 
 
 
Factor H related protein def:, CFHR1-5, AR, AD
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C8 def:, C8A, C8B, C8G
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C4 def:, C4A, C4B, AR
 
 
 
 
Factor I def:, AR
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C9 def:, C9 mild susceptibility
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thrombomodulin def:, THBD, AD
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Membrane cofactor protein def:, CD46, AD
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Disseminated Nisserial Infections

C5 Deficiency

C6 Deficiency

  • C6 is structurally similar to other terminal complement components, C5b, C7, C8, and C9, all of which participate in the formation of the membrane attack complex (MAC).[6]
  • C6 deficiency is a genetic disorder presenting as an increased susceptibility to invasive Neisseria meningitidis infections.[7]
  • Complete C6 deficiency presents with recurrent Neisseria meningitidis infection and it should be distinguished from subtotal C6 deficiency in which the complement protein is functionally active and there is no association with Neisserial infections.[8]

C7 Deficiency

  • C7 is part of the membrane attack complex (MAC) and the deficiency of this protein leads to the failure of membrane attack complex (MAC) formation.
  • Patients with C7 deficiency present with recurrent meningococcal infection.[9]
  • It can also rarely present with severe and aggressive pyoderma gangrenum.[10]
  • Patients can also suffer from recurrent otitis media, tonsilitis and chronic mucopurulent rhinitis with subsequent pansinusitis complicated by nasal polyposis.[11]
  • Antibiotics prophylaxis can be used to decrease the number of ear nose and throat (ENT) infections.

References

  1. Michael Corvini, Christopher Randolph & Steven I. Aronin (2004). "Complement C7 deficiency presenting as recurrent aseptic meningitis". Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 93 (2): 200–205. doi:10.1016/S1081-1206(10)61476-7. PMID 15328683. Unknown parameter |month= ignored (help)
  2. Miller, Michael E.; Nilsson, Ulf R. (1970). "A Familial Deficiency of the Phagocytosis-Enhancing Activity of Serum Related to a Dysfunction of the Fifth Component of Complement (C5)". New England Journal of Medicine. 282 (7): 354–358. doi:10.1056/NEJM197002122820702. ISSN 0028-4793.
  3. A. Orren (2000). "Molecular mechanisms of complement component C6 deficiency; a hypervariable exon 6 region responsible for three of six reported defects". Clinical and experimental immunology. 119 (2): 255–258. PMID 10632659. Unknown parameter |month= ignored (help)
  4. R. Snyderman, D. T. Durack, G. A. McCarty, F. E. Ward & L. Meadows (1979). "Deficiency of the fifth component of complement in human subjects. Clinical, genetic and immunologic studies in a large kindred". The American journal of medicine. 67 (4): 638–645. PMID 495634. Unknown parameter |month= ignored (help)
  5. O. Sanal, M. Loos, F. Ersoy, G. Kanra, G. Secmeer & I. Tezcan (1992). "Complement component deficiencies and infection: C5, C8 and C3 deficiencies in three families". European journal of pediatrics. 151 (9): 676–679. PMID 1396929. Unknown parameter |month= ignored (help)
  6. Z. Zhu, T. P. Atkinson, K. T. Hovanky, S. B. Boppana, Y. L. Dai, P. Densen, R. C. Go, J. S. Jablecki & J. E. Volanakis (2000). "High prevalence of complement component C6 deficiency among African-Americans in the south-eastern USA". Clinical and experimental immunology. 119 (2): 305–310. PMID 10632667. Unknown parameter |month= ignored (help)
  7. M. R. Moya-Quiles, M. V. Bernardo-Pisa, P. Martinez, L. Gimeno, A. Bosch, G. Salgado, H. Martinez-Banaclocha, J. Eguia, J. A. Campillo, M. Muro, J. B. Vidal-Bugallo, M. R. Alvarez-Lopez & A. M. Garcia-Alonso (2013). "Complement component C6 deficiency in a Spanish family: implications for clinical and molecular diagnosis". Gene. 521 (1): 204–206. doi:10.1016/j.gene.2013.03.027. PMID 23537992. Unknown parameter |month= ignored (help)
  8. A. Orren (2000). "Molecular mechanisms of complement component C6 deficiency; a hypervariable exon 6 region responsible for three of six reported defects". Clinical and experimental immunology. 119 (2): 255–258. PMID 10632659. Unknown parameter |month= ignored (help)
  9. L. J. Egan, A. Orren, J. Doherty, R. Wurzner & C. F. McCarthy (1994). "Hereditary deficiency of the seventh component of complement and recurrent meningococcal infection: investigations of an Irish family using a novel haemolytic screening assay for complement activity and C7 M/N allotyping". Epidemiology and infection. 113 (2): 275–281. PMID 7523157. Unknown parameter |month= ignored (help)
  10. L. J. Egan, A. Orren, J. Doherty, R. Wurzner & C. F. McCarthy (1994). "Hereditary deficiency of the seventh component of complement and recurrent meningococcal infection: investigations of an Irish family using a novel haemolytic screening assay for complement activity and C7 M/N allotyping". Epidemiology and infection. 113 (2): 275–281. PMID 7523157. Unknown parameter |month= ignored (help)
  11. A. Srotova, J. Litzman, S. Rumlarova, M. Drahosova, D. Bartonkova, I. Krcmova, A. Roberts, S. Jolles & P. Kralickova. "[Recurrent meningitis and inherited complement deficiency]". Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne. 65 (4): 238–242. PMID 28078901.