Complement deficiencies
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Immunodeficiency Main Page |
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
- C5 deficiency is the basis of lack of phagocytosis-enhancing activity of serum. [2]
- C5 deficiency leads to the failure to form the membrane attack complex (MAC) which is responsible for the lytic action of the complement.[3]
- It is associated with recurrent disseminated gonococcal infection.[4]
- Patients present with recurrent meningitis and meningococcemia, as well as recurrent purulent otitis media.[5]
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 complement protein leads to the loss of complement lytic function.[9]
- Patients with C7 deficiency present with recurrent meningococcal infection.[10]
- It can also rarely present with severe and aggressive pyoderma gangrenum.[11]
- Patients can also suffer from recurrent otitis media, tonsilitis and chronic mucopurulent rhinitis with subsequent pansinusitis complicated by nasal polyposis.[12]
- Antibiotics prophylaxis can be used to decrease the number of ear nose and throat (ENT) infections.
C8 Deficiency
- C8 deficiency results in the failure of membrane attack complex (MAC) assembly.[13]
- Patients suffer from recurrent neisserial infections, predominantly with meningococcus infection of rare serotypes.[14]
- It can present with juvenile chronic arthritis.[15]
- Prophylaxis with conjugate polysaccharide vaccines is recommended and antibiotic prophylaxis should be considered in individual cases.[16]
References
- ↑ 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) - ↑ 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.
- ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ Sung Hoon Sim, Jung Yeon Heo, Eui-Chong Kim & Kang-Won Choe (2013). "A case of meningococcal sepsis and meningitis with complement 7 deficiency in a military trainee". Infection & chemotherapy. 45 (1): 94–98. doi:10.3947/ic.2013.45.1.94. PMID 24265955. Unknown parameter
|month=ignored (help) - ↑ 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) - ↑ 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) - ↑ 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.
- ↑ L. Saucedo, L. Ackermann, A. E. Platonov, A. Gewurz, R. M. Rakita & P. Densen (1995). "Delineation of additional genetic bases for C8 beta deficiency. Prevalence of null alleles and predominance of C-->T transition in their genesis". Journal of immunology (Baltimore, Md. : 1950). 155 (10): 5022–5028. PMID 7594510. Unknown parameter
|month=ignored (help) - ↑ S. C. Ross & P. Densen (1984). "Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency". Medicine. 63 (5): 243–273. PMID 6433145. Unknown parameter
|month=ignored (help) - ↑ N. M. Wulffraat, E. A. Sanders, C. A. Fijen, A. Hannema, W. Kuis & B. J. Zegers (1994). "Deficiency of the beta subunit of the eighth component of complement presenting as arthritis and exanthem". Arthritis and rheumatism. 37 (11): 1704–1706. PMID 7980680. Unknown parameter
|month=ignored (help) - ↑ 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.