Skip to main content
SpringerLink
Log in

Complement C3 Deficiency

  • Reference work entry
  • First Online:
Encyclopedia of Medical Immunology

  • 8 Accesses

Definition

Genetic C3 deficiency is a rare primary immunodeficiency disorder in cases of complete loss of C3 production with both affected alleles; it may be associated with inflammatory disorders in monoallelic defects. Secondary C3consumptions are associated with renal diseases.

Introduction

Complement is a crucial network for both innate and adaptive immune responses. The third component of complement (C3) plays a pivotal role in the complement pathway; it is one of the sources of these biologically active fragments that induce pro-inflammatory responses and mark the particles for clearance by cell lysis or phagocytosis and for activation and control of adaptive immunity (Ricklin et al. 2010).

Given the importance of C3 in the immune response, it is not surprising that its deficiency has been associated with clinical phenotypes. Complete C3 deficiency is a rare disorder with severe recurrent bacterial infections and immune complex-mediated diseases, particularly glomerulonephritis....

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 449.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alper CA, Colten HR, Rosen FS, Rabson AR, Macnab GM, Gear JS. Homozygous deficiency of C3 in a patient with repeated infections. Lancet. 1972;2(7788):1179–81.

    Article  CAS  Google Scholar 

  • Appel GB, Cook HT, Hageman G, Jennette JC, Kashgarian M, Kirschfink M, Lambris JD, Lanning L, Lutz HU, Meri S, Rose NR, Salant DJ, Sethi S, Smith RJ, Smoyer W, Tully HF, Tully SP, Walker P, Welsh M, Würzner R, Zipfel PF. Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. J Am Soc Nephrol. 2005;16(5):1392–403.

    Article  Google Scholar 

  • Borzy MS1, Gewurz A, Wolff L, Houghton D, Lovrien E. Inherited C3 deficiency with recurrent infections and glomerulonephritis. Am J Dis Child. 1988;142(1):79–83.

    CAS  Google Scholar 

  • Botto M, Fong KY, So AK, Rudge A, Walport MJ. Molecular basis of hereditary C3 deficiency. J Clin Invest. 1990;86(4):1158–63.

    Article  CAS  Google Scholar 

  • Botto M, Fong KY, So AK, Barlow R, Routier R, Morley BJ, Walport MJ. Homozygous hereditary C3 deficiency due to a partial gene deletion. Proc Natl Acad Sci U S A. 1992;89(11):4957–61.

    Article  CAS  Google Scholar 

  • Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, Pinto S, Goodship TH, Alberti M, Ribes D, Valoti E, Remuzzi G, Noris M, European Working Party on Complement Genetics in Renal Diseases. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol. 2013;24(3):475–86.

    Article  CAS  Google Scholar 

  • Da Silva Reis E, Baracho GV, Sousa Lima A, Farah CS, Isaac L. Homozygous hereditary C3 deficiency due to a premature stop codon. J Clin Immunol. 2002;22(6):321–30.

    Article  Google Scholar 

  • Fong KY, Botto M, Walport MJ, So AK. Genomic organization of human complement component C3. Genomics. 1990;7(4):579–86.

    Article  CAS  Google Scholar 

  • Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey M-A, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschênes G, Lebranchu Y, Zuber J, Loirat C. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554–62.

    Article  CAS  Google Scholar 

  • Ghannam A, Pernollet M, Fauquert J-L, Monnier N, Ponard D, Villiers M-B, Péguet-Navarro J, Tridon A, Lunardi J, Gerlier D, Drouet C. Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells. J Immunol. 2008;181(7):5158–66.

    Article  CAS  Google Scholar 

  • Ghannam A, Fauquert J-L, Thomas C, Kemper C, Drouet C. Human complement C3 deficiency: Th1 induction requires T cell-derived complement C3a and CD46 activation. Mol Immunol. 2014;58(1):98–107.

    Article  CAS  Google Scholar 

  • Goldberg M, Fremeaux-Bacchi V, Koch P, Fishelson Z, Katz Y. A novel mutation in the C3 gene and recurrent invasive pneumococcal infection: a clue for vaccine development. Mol Immunol. 2011;48(15–16):1926–31.

    Article  CAS  Google Scholar 

  • Grumach AS, Vilela MM, Gonzalez CH, Starobinas N, Pereira AB, Dias-da-Silva W, Carneiro-Sampaio MM. Inherited C3 deficiency of the complement system. Braz J Med Biol Res. 1988;21(2):247–57.

    CAS  Google Scholar 

  • Grumach AS, Kirschfink M. Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach. Mol Immunol. 2014;61(2):110–7.

    Article  CAS  Google Scholar 

  • Heurich M, Martínez-Barricarte R, Francis NJ, Roberts DL, Rodríguez de Córdoba S, Morgan BP. Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc Natl Acad Sci U S A. 2011;108(21):8761–6.

    Article  Google Scholar 

  • Hsieh KH, Lin CY, Lee TC. Complete absence of the third component of complement in a patient with repeated infections. Clin Immunol Immunopathol. 1981;20(3):305–12.

    Article  CAS  Google Scholar 

  • Huang JL, Lin CY. A hereditary C3 deficiency due to aberrant splicing of exon 10. Clin Immunol Immunopathol. 1994;73(2):267–73.

    Article  CAS  Google Scholar 

  • Jiménez-Reinoso A, López-Lera A, Marin AVM, López-Rela J, Martínez-Naves E, de Córdoba SR, Román-Ortiz E, López-Trascasa M, Regueiro JR. Differential impairment of dendritic, B and T cell differentiation in congenital primary (C3-deficient) as opposed to secondary (factor I-deficient) human plasma C3 deficiencies. Mol Immunol. 2015;67(1):147–8 [abstract].

    Google Scholar 

  • Katz Y, Wetsel RA, Schlesinger M, Fishelson Z. Compound heterozygous complement C3 deficiency. Immunology. 1995;84(1):5–7.

    CAS  Google Scholar 

  • Kida M, Fujioka H, Kosaka Y, Hayashi K, Sakiyama Y, Ariga T. The first confirmed case with C3 deficiency caused by compound heterozygous mutations in the C3 gene; a new aspect of pathogenesis for C3 deficiency. Blood Cells Mol Dis. 2008;40(3):410–3.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Matsuyama W, Nakagawa M, Takashima H, Muranaga F, Sano Y, Osame M. Identification of a novel mutation (Tyr1081Ter) in sisters with hereditary component C3 deficiency and SLE-like symptoms. Hum Mutat. 2001;17(1):79.

    Article  CAS  Google Scholar 

  • Matsumoto T, Fan X, Ishikawa E, Ito M, Amano K, Toyoda H, Komada Y, Ohishi K, Katayama N, Yoshida Y, Matsumoto M, Fujimura Y, Ikejiri M, Wada H, Miyata T. Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation. Int J Hematol. 2014;100(5):437–42.

    Article  CAS  Google Scholar 

  • Mullins RF, Russell SR, Anderson DH, Hageman GS. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J. 2000;14(7):835–46.

    Article  CAS  Google Scholar 

  • Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5(10):1844–59.

    Article  CAS  Google Scholar 

  • Okura Y, Yamada M, Takezaki S, Nawate M, Takahashi Y, Kida M, Kawamura N, Ariga T. Novel compound heterozygous mutations in the C3 gene: hereditary C3 deficiency. Pediatr Int. 2011;53(2):e16–9.

    Article  Google Scholar 

  • Reis ES, Falcão DA, Isaac L. Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H. Scand J Immunol. 2006;68(4):445–55.

    Google Scholar 

  • Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785–97.

    Article  CAS  Google Scholar 

  • Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY. Reference distributions for complement proteins C3 and C4: a practical, simple and clinically relevant approach in a large cohort. J Clin Lab Anal. 2004;18(1):1–8.

    Article  CAS  Google Scholar 

  • Santos-Valente E, Reisli I, Artaç H, Ott R, Sanal Ö, Boztug K. A novel mutation in the complement component 3 gene in a patient with selective IgA deficiency. J Clin Immunol. 2013;33(1):127–33.

    Article  Google Scholar 

  • Schramm EC, Clark SJ, Triebwasser MP, Raychaudhuri S, Seddon JM, Atkinson JP. Genetic variants in the complement system predisposing to age-related macular degeneration: a review. Mol Immunol. 2014;61(2):118–25.

    Article  CAS  Google Scholar 

  • Schramm EC, Roumenina LT, Rybkine T, Chauvet S, Vieira-Martins P, Hue C, Maga T, Valoti E, Wilson V, Jokiranta S, Smith RJ, Noris M, Goodship T, Atkinson JP, Fremeaux-Bacchi V. Functional mapping of the interactions between complement C3 and regulatory proteins using atypical hemolytic uremic syndrome-associated mutations. Blood. 2015;125(15):2359–69.

    Article  CAS  Google Scholar 

  • Seddon JM, Yu Y, Miller EC, Reynolds R, Tan PL, Gowrisankar S, Goldstein JI, Triebwasser M, Anderson HE, Zerbib J, Kavanagh D, Souied E, Katsanis N, Daly MJ, Atkinson JP, Raychaudhuri S. Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat Genet. 2013;45(11):1366–70.

    Article  CAS  Google Scholar 

  • Sfyroera G, Ricklin D, Reis ES, Chen H, Wu EL, Kaznessis YN, Ekdahl KN, Nilsson B, Lambris JD. Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants of complement activity. J Immunol. 2015;194(7):3305–16.

    Article  CAS  Google Scholar 

  • Singer L, Whitehead WT, Akama H, Katz Y, Fishelson Z, Wetsel RA. Inherited human complement C3 deficiency. An amino acid substitution in the betachain (ASP549 to ASN) impairs C3 secretion. J Biol Chem. 1994;269(45):28494–9.

    CAS  Google Scholar 

  • Singer L, Van Hee ML, Lokki ML, Kramer J, Borzy MS, Wetsel RA. Inherited complement C3 deficiency: reduced C3 mRNA and protein levels in a Laotian kindred. Clin Immunol Immunopathol. 1996;81(3):244–52.

    Article  CAS  Google Scholar 

  • Tsukamoto H, Horiuchi T, Kokuba H, Nagae S, Nishizaka H, Sawabe T, Harashima S, Himeji D, Koyama T, Otsuka J, Mitoma H, Kimoto Y, Hashimura C, Kitano E, Kitamura H, Furue M, Harada M. Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus. Biochem Biophys Res Commun. 2005;330(1):298–304.

    Article  CAS  Google Scholar 

  • Ulbrich AG, Florido MP, Nudelman V, Reis ES, Baracho GV, Isaac L. Hereditary human complement C3 deficiency owing to reduced levels of C3 mRNA. Scand J Immunol. 2001;53(6):622–6.

    Article  CAS  Google Scholar 

  • Yates JRW, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT, Genetic Factors in AMD Study Group. Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 2007;357(6):553–61.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. GREPI EA7408, University Grenoble Alpes, Grenoble, France

    Arije Ghannam & Christian Drouet

  2. KininX SAS, Grenoble, France

    Arije Ghannam

Authors
  1. Arije Ghannam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Drouet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Drouet .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Columbia University Vagelos, College of Physicians and Surgeons, NewYork-Presbyterian Morgan, Stanley Children’s Hospital, New York, NY, USA

    Jordan Scott Orange

  2. Division of Allergy and Immunology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, The Woodlands, TX, USA

    Javier Chinen

Section Editor information

  1. University of Pennsylvania, Philadelphia, USA

    Kathleen Sullivan

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Ghannam, A., Drouet, C. (2020). Complement C3 Deficiency. In: Orange, J.S., Chinen, J. (eds) Encyclopedia of Medical Immunology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8678-7_2

Download citation

Publish with us

Policies and ethics

Search

Navigation