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Complement Deficiencies in Systemic Lupus Erythematosus

  • Autoimmunity (TK Tarrant, Section Editor)
  • Published:
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Abstract

The complement system is a major, multifunctional part of innate immunity and serves as a bridge between the innate and adaptive immune systems. It consists of more than 30 distinct proteins that interact with one another in a specific sequence. There are three pathways of complement activation: the classical, the lectin, and the alternative pathways. The three pathways are initiated by distinct mechanisms, but they all generate the same core set of effector molecules. Inherited complete deficiencies in complement components are generally very rare and predispose to infections and autoimmune disease. One of the better described associations is between deficiencies in early classical pathway components and the development of systemic lupus erythematosus. The goal of this review will be to discuss the associations between and the causal mechanisms of complement deficiencies and systemic lupus erythematosus.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Frank MM. Complement disorders and hereditary angioedema. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S262–71. This paper provides a more detailed review of the complement activation pathways and their regulators as well as a brief discussion of deficiencies in the complement system.

    Article  PubMed  Google Scholar 

  2. Walport MJ. Complement. First of two parts. N Engl J Med. 2001;344(14):1058–66.

    Article  CAS  PubMed  Google Scholar 

  3. Rus H, Cudrici C, Niculescu F. The role of the complement system in innate immunity. Immunol Res. 2005;33(2):103–12.

    Article  CAS  PubMed  Google Scholar 

  4. Carroll MC. The role of complement in B cell activation and tolerance. Adv Immunol. 2000;74:61–88.

    Article  CAS  PubMed  Google Scholar 

  5. Ballanti E et al. Complement and autoimmunity. Immunol Res. 2013;56(2–3):477–91. This paper provides recent, thorough discussion of the complement system and its role in the pathogenesis of a spectrum of autoimmune diseases.

    Article  CAS  PubMed  Google Scholar 

  6. Chen M, Daha MR, Kallenberg CG. The complement system in systemic autoimmune disease. J Autoimmun. 2010;34(3):J276–86.

    Article  CAS  PubMed  Google Scholar 

  7. Walport MJ. Complement and systemic lupus erythematosus. Arthritis Res. 2002;4 Suppl 3:S279–93.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity. 2007;40(8):560–6.

    Article  CAS  PubMed  Google Scholar 

  9. Wen L, Atkinson JP, Giclas PC. Clinical and laboratory evaluation of complement deficiency. J Allergy Clin Immunol. 2004;113(4):585–93. quiz 594.

    Article  CAS  PubMed  Google Scholar 

  10. Frank MM. Complement deficiencies. Pediatr Clin N Am. 2000;47(6):1339–54.

    Article  CAS  Google Scholar 

  11. Pettigrew HD, Teuber SS, Gershwin ME. Clinical significance of complement deficiencies. Ann N Y Acad Sci. 2009;1173:108–23. This paper provides a more comprehensive overview of the diversity of clinical manifestations of deficiencies in the complement system.

    Article  CAS  PubMed  Google Scholar 

  12. Lewis MJ, Botto M. Complement deficiencies in humans and animals: links to autoimmunity. Autoimmunity. 2006;39(5):367–78.

    Article  CAS  PubMed  Google Scholar 

  13. Walport MJ. Complement. Second of two parts. N Engl J Med. 2001;344(15):1140–4.

    Article  CAS  PubMed  Google Scholar 

  14. Inai S et al. Inherited deficiencies of the late-acting complement components other than C9 found among healthy blood donors. Int Arch Allergy Appl Immunol. 1989;90(3):274–9.

    Article  CAS  PubMed  Google Scholar 

  15. Deapen D et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum. 1992;35(3):311–8.

    Article  CAS  PubMed  Google Scholar 

  16. Sturfelt G, Truedsson L. Complement and its breakdown products in SLE. Rheumatology (Oxford). 2005;44(10):1227–32.

    Article  CAS  Google Scholar 

  17. Botto M, Walport MJ. C1q, autoimmunity and apoptosis. Immunobiology. 2002;205(4–5):395–406.

    Article  CAS  PubMed  Google Scholar 

  18. Sontheimer RD, Racila E, Racila DM. C1q: its functions within the innate and adaptive immune responses and its role in lupus autoimmunity. J Invest Dermatol. 2005;125(1):14–23.

    Article  CAS  PubMed  Google Scholar 

  19. Prodeus AP et al. A critical role for complement in maintenance of self-tolerance. Immunity. 1998;9(5):721–31.

    Article  CAS  PubMed  Google Scholar 

  20. Gullstrand B et al. Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells. Clin Exp Immunol. 2009;156(2):303–11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Lood C et al. C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis Rheum. 2009;60(10):3081–90.

    Article  CAS  PubMed  Google Scholar 

  22. Fraser DA et al. C1q and MBL, components of the innate immune system, influence monocyte cytokine expression. J Leukoc Biol. 2006;80(1):107–16.

    Article  CAS  PubMed  Google Scholar 

  23. Botto M et al. Complement in human diseases: lessons from complement deficiencies. Mol Immunol. 2009;46(14):2774–83.

    Article  CAS  PubMed  Google Scholar 

  24. Manderson AP, Botto M, Walport MJ. The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol. 2004;22:431–56.

    Article  CAS  PubMed  Google Scholar 

  25. Vassallo G et al. Clinical variability and characteristic autoantibody profile in primary C1q complement deficiency. Rheumatology (Oxford). 2007;46(10):1612–4.

    Article  CAS  Google Scholar 

  26. Boteva L et al. Genetically determined partial complement C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations. Am J Hum Genet. 2012;90(3):445–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Jonsson G et al. Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency. Rheumatology (Oxford). 2007;46(7):1133–9.

    Article  CAS  Google Scholar 

  28. Palarasah Y et al. Novel assays to assess the functional capacity of the classical, the alternative and the lectin pathways of the complement system. Clin Exp Immunol. 2011;164(3):388–95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Ohlenschlaeger T et al. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med. 2004;351(3):260–7.

    Article  CAS  PubMed  Google Scholar 

  30. Steinsson K, Erlendsson K, Valdimarsson H. Successful plasma infusion treatment of a patient with C2 deficiency and systemic lupus erythematosus: clinical experience over forty-five months. Arthritis Rheum. 1989;32(7):906–13.

    CAS  PubMed  Google Scholar 

  31. Erlendsson K et al. Reciprocal changes in complement activity and immune-complex levels during plasma infusion in a C2-deficient SLE patient. Lupus. 1993;2(3):161–5.

    Article  CAS  PubMed  Google Scholar 

  32. Hudson-Peacock MJ et al. Systemic lupus erythematosus complicating complement type 2 deficiency: successful treatment with fresh frozen plasma. Br J Dermatol. 1997;136(3):388–92.

    Article  CAS  PubMed  Google Scholar 

  33. Mehta P et al. SLE with C1q deficiency treated with fresh frozen plasma: a 10-year experience. Rheumatology (Oxford). 2010;49(4):823–4.

    Article  Google Scholar 

  34. Martini PG et al. Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases. BMC Immunol. 2010;11:43. This paper provides proof of concept that recombinant complement proteins may be successfully produced and may restore functional activity in the setting of complement deficiency.

    Article  PubMed Central  PubMed  Google Scholar 

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Conflict of Interest

Angela Bryan and Eveline Wu declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Pediatric Rheumatology Division, Duke University Children’s Health Center, 2301 Erwin Road, Durham, NC, 27710, USA

    Angela R. Bryan

  2. Division of Pediatric Allergy/Immunology and Rheumatology, University of North Carolina at Chapel Hill, 250 Bell Tower Drive CB# 7231, Chapel Hill, NC, 27599, USA

    Eveline Y. Wu

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  1. Angela R. Bryan
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  2. Eveline Y. Wu
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Correspondence to Eveline Y. Wu.

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This article is part of the Topical Collection on Autoimmunity

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Bryan, A.R., Wu, E.Y. Complement Deficiencies in Systemic Lupus Erythematosus. Curr Allergy Asthma Rep 14, 448 (2014). https://doi.org/10.1007/s11882-014-0448-2

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  • DOI: https://doi.org/10.1007/s11882-014-0448-2

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