Complement Deficiencies

  • Kathleen Sullivan
  • Martha M. Eibl
  • Melinda Erdős
  • László Maródi
  • Hermann M. Wolf
  • Maryam Mahmoudi
  • Nima Rezaei
Chapter

Abstract

Although the complement system was first described at the turn of the twentieth century, it was not until 1960 that the first patient with a genetically determined complement deficiency was identified. Since then, deficiencies have been described for nearly all of the components of the complement system. Individuals with genetically determined complement deficiencies have a variety of clinical presentations. Most patients present with an increased susceptibility to infections, others with a variety of rheumatic diseases, still others with angioedema, and in rare instances, patients may even be asymptomatic. The elucidation of the pathophysiological basis for the different clinical presentations of complement-deficient individuals has contributed to a better understanding of the physiological role of complement in normal individuals.

Keywords

Correct Answer Hemolytic Uremic Syndrome Complement Component Meningococcal Disease Neisseria Meningitidis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Figueroa JE, Densen P (1991) Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 4(3):359–395PubMedGoogle Scholar
  2. 2.
    Hyatt AC, Altenburger KM, Johnston RB Jr, Winkelstein JA (1981) Increased susceptibility to severe pyogenic infections in patients with an inherited deficiency of the second component of complement. J Pediatr 98(3):417–419PubMedCrossRefGoogle Scholar
  3. 3.
    Truedsson L, Bengtsson AA, Sturfelt G (2007) Complement deficiencies and systemic lupus erythematosus. Autoimmunity 40(8):560–566PubMedCrossRefGoogle Scholar
  4. 4.
    Hartmann D, Fremeaux-Bacchi V, Weiss L, Meyer A, Blouin J, Hauptmann G, Kazatchkine M, Uring-Lambert B (1997) Combined heterozygous deficiency of the classical complement pathway proteins C2 and C4. J Clin Immunol 17(2):176–184PubMedCrossRefGoogle Scholar
  5. 5.
    Steinsson K, Erlendsson K, Valdimarsson H (1989) Successful plasma infusion treatment of a patient with C2 deficiency and systemic lupus erythematosus: clinical experience over forty-five months. Arthritis Rheum 32(7):906–913PubMedGoogle Scholar
  6. 6.
    Johnson CA, Densen P, Hurford RK Jr, Colten HR, Wetsel RA (1993) Type I human complement C2 deficiency. A 28-base pair gene deletion causes skipping of exon 6 during RNA splicing. J Biol Chem 268(3):2268PubMedGoogle Scholar
  7. 7.
    Sullivan KE, Winkelstein JA (1994) Prenatal diagnosis of heterozygous deficiency of the ­second component of complement. Clin Diagn Lab Immunol 1(5):606–607PubMedGoogle Scholar
  8. 8.
    Singer L, Colten HR, Wetsel RA (1994) Complement C3 deficiency: human, animal, and experimental models. Pathobiology 62(1):14–28PubMedCrossRefGoogle Scholar
  9. 9.
    Ghannam A, Pernollet M, Fauquert JL, Monnier N, Ponard D, Villiers MB, Peguet-Navarro J, Tridon A, Lunardi J, Gerlier D, Drouet C (2008) Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells. J Immunol 181(7):5158–5166PubMedGoogle Scholar
  10. 10.
    Petri M, Watson R, Winkelstein JA, McLean RH (1993) Clinical expression of systemic lupus erythematosus in patients with C4A deficiency. Medicine (Baltimore) 72(4):236–244Google Scholar
  11. 11.
    Welch TR, Brickman C, Bishof N, Maringhini S, Rutkowski M, Frenzke M, Kantor N (1998) The phenotype of SLE associated with complete deficiency of complement isotype C4A. J Clin Immunol 18(1):48–51PubMedCrossRefGoogle Scholar
  12. 12.
    Sullivan KE, Kim NA, Goldman D, Petri MA (1999) C4A deficiency due to a 2 bp insertion is increased in patients with systemic lupus erythematosus. J Rheumatol 26(10):2144–2147PubMedGoogle Scholar
  13. 13.
    Fukumori Y, Horiuchi T (1998) Terminal complement component deficiencies in Japan. Exp Clin Immunogenet 15(4):244–248PubMedCrossRefGoogle Scholar
  14. 14.
    Platonov AE, Beloborodov VB, Vershinina IV (1993) Meningococcal disease in patients with late complement component deficiency: studies in the U.S.S.R. Medicine (Baltimore) 72(6):374–392Google Scholar
  15. 15.
    Platonov AE, Vershinina IV, Kuijper EJ, Borrow R, Kayhty H (2003) Long term effects of vaccination of patients deficient in a late complement component with a tetravalent meningococcal polysaccharide vaccine. Vaccine 21(27–30):4437–4447PubMedCrossRefGoogle Scholar
  16. 16.
    Figueroa J, Andreoni J, Densen P (1993) Complement deficiency states and meningococcal disease. Immunol Res 12(3):295–311PubMedCrossRefGoogle Scholar
  17. 17.
    Boyer JT, Gall EP, Norman ME, Nilsson UR, Zimmerman TS (1975) Hereditary deficiency of the seventh component of complement. J Clin Invest 56(4):905–913PubMedCrossRefGoogle Scholar
  18. 18.
    Tedesco F (2008) Inherited complement deficiencies and bacterial infections. Vaccine 26(Suppl 8):I3–I8PubMedCrossRefGoogle Scholar
  19. 19.
    Ross SC, Densen P (1984) Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 63(5):243–273Google Scholar
  20. 20.
    Fernie BA, Hobart MJ (1998) Complement C7 deficiency: seven further molecular defects and their associated marker haplotypes. Hum Genet 103(4):513–519PubMedCrossRefGoogle Scholar
  21. 21.
    van Campagne Lookeren M, Wiesmann C, Brown EJ (2007) Macrophage complement receptors and pathogen clearance. Cell Microbiol 9(9):2095–2102CrossRefGoogle Scholar
  22. 22.
    Genel F, Atlihan F, Gulez N, Sjoholm AG, Skattum L, Truedsson L (2006) Properdin deficiency in a boy with fulminant meningococcal septic shock. Acta Paediatr 95(11):1498–1500PubMedCrossRefGoogle Scholar
  23. 23.
    Rijkers GT, Sanders LA, Zegers BJ (1993) Anti-capsular polysaccharide antibody deficiency states. Immunodeficiency 5(1):1–21PubMedGoogle Scholar
  24. 24.
    Castagliuolo PP, Nisini R, Quinti I, Fattorossi A, D’Amelio R (1986) Immunoglobulin deficiencies and meningococcal disease. Ann Allergy 57(1):68–70PubMedGoogle Scholar
  25. 25.
    Bork K, Wulff K, Hardt J, Witzke G, Staubach P (2009) Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol 124(1):129–134PubMedCrossRefGoogle Scholar
  26. 26.
    Zuraw BL (2008) Clinical practice. Hereditary angioedema. N Engl J Med 359(10):1027–1036PubMedCrossRefGoogle Scholar
  27. 27.
    Cicardi M, Castelli R, Zingale LC, Agostoni A (1997) Side effects of long-term prophylaxis with attenuated androgens in hereditary angioedema: comparison of treated and untreated patients. J Allergy Clin Immunol 99(2):194–196PubMedCrossRefGoogle Scholar
  28. 28.
    Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G, Del-Favero J, Plaisance S, Claes B, Lambrechts D, Zoja C, Remuzzi G, Conway EM (2009) Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med 361(4):345–357PubMedCrossRefGoogle Scholar
  29. 29.
    Richards A, Kavanagh D, Atkinson JP (2007) Inherited complement regulatory protein deficiency predisposes to human disease in acute injury and chronic inflammatory states the examples of vascular damage in atypical hemolytic uremic syndrome and debris accumulation in age-related macular degeneration. Adv Immunol 96:141–177PubMedCrossRefGoogle Scholar
  30. 30.
    Fakhouri F, de Jorge EG, Brune F, Azam P, Cook HT, Pickering MC (2010) Treatment with human complement factor H rapidly reverses renal complement deposition in factor H-deficient mice. Kidney Int 78(3):279–286PubMedCrossRefGoogle Scholar
  31. 31.
    Zimmerhackl LB, Besbas N, Jungraithmayr T, van de Kar N, Karch H, Karpman D, Landau D, Loirat C, Proesmans W, Prufer F, Rizzoni G, Taylor MC (2006) Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome. Semin Thromb Hemost 32(2):113–120PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Kathleen Sullivan
    • 1
  • Martha M. Eibl
    • 2
  • Melinda Erdős
    • 3
  • László Maródi
    • 3
  • Hermann M. Wolf
    • 2
  • Maryam Mahmoudi
    • 4
  • Nima Rezaei
    • 5
    • 6
    • 7
  1. 1.Division of Allergy and ImmunologyChildren’s Hospital of Philadelphia, University of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Department of PediatricsImmunological Outpatient Clinic, Biomedical Research InstituteViennaAustria
  3. 3.Department of Infectious and Pediatric ImmunologyMedical and Health Science Center, University of DebrecenDebrecenHungary
  4. 4.Department of Nutrition and Biochemistry, School of Public HealthTehran University of Medical SciencesTehranIran
  5. 5.Department of ImmunologyResearch Center for Immunodeficiencies, Children’s Medical Center HospitalTehranIran
  6. 6.Molecular Immunology Research CenterTehranIran
  7. 7.Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran

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