Skip to main content
SpringerLink
Log in

Complement Deficiencies

  • Chapter
  • First Online:
Primary Immunodeficiency Diseases

Abstract

The complement system is an essential part of innate immunity, with vital interconnections with the adaptive immune system. The complement system has several interconnections with the adaptive immunity, e.g. via bridging antibody recognition to complement-dependent opsonization and lowering the threshold for antigenic B-cell stimulation and regulating T cells. The complement system is activated via the classical, lectin or alternative pathway, which are all initiated by different structures and by different mechanisms. Complement deficiencies, acquired or hereditary, have been recognized for almost all of the known components of the complement system. Acquired deficiency may be caused by infections or immune-complex disorders. Most inherited deficiencies of complement components are expressed in an autosomal recessive pattern. Primary complement deficiencies are in particular associated with an increased susceptibility to recurrent and invasive bacterial infections and with autoimmune disorders. Although complement deficiencies are uncommon in the general population, individuals with such deficiencies frequently suffer from serious and often life-threatening diseases, which need specific therapy, including vaccines and easy access to antibiotics. Therefore, patients with recurrent or invasive bacterial infections, certain kidney diseases, familial autoimmune disease or angioedema, should always be tested for complement deficiencies. If a complement deficiency is identified, management focuses on the associated disease, such as infection or autoimmunity. Prevention of infections by vaccination and immediate treatment with appropriate antibiotics are crucial. In some of these patients, antibiotic prophylaxis may be considered, and special attention should be given to vaccination against encapsulated organisms. Also, early recognition and management of autoimmune diseases are necessary.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
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

  1. Agostoni A, Cicardi M, Cugno M, Zingale LC, Gioffre D, Nussberger J. Angioedema due to angiotensin-converting enzyme inhibitors. Immunopharmacology. 1999;44:21–5.

    CAS  PubMed  Google Scholar 

  2. Agrawal A, Shrive AK, Greenhough TJ, Volanakis JE. Topology and structure of the C1q-binding site on C-reactive protein. J Immunol. 2001;166:3998–4004.

    CAS  PubMed  Google Scholar 

  3. Ambrus G, Gal P, Kojima M, Szilagyi K, Balczer J, Antal J, Graf L, Laich A, Moffatt BE, Schwaeble W, Sim RB, Zavodszky P. Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and −2: a study on recombinant catalytic fragments. J Immunol. 2003;170:1374–82.

    CAS  PubMed  Google Scholar 

  4. Benard M, Raoult E, Vaudry D, Leprince J, Falluel-Morel A, Gonzalez BJ, Galas L, Vaudry H, Fontaine M. Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Mol Immunol. 2008;45:3767–74.

    CAS  PubMed  Google Scholar 

  5. Biesma DH, Hannema AJ, van Velzen-Blad H, Mulder L, van Zwieten R, Kluijt I, Roos D. A family with complement factor D deficiency. J Clin Invest. 2001;108:233–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Blanch A, Roche O, Urrutia I, Gamboa P, Fontan G, Lopez-Trascasa M. First case of homozygous C1 inhibitor deficiency. J Allergy Clin Immunol. 2006;118:1330–5.

    PubMed  Google Scholar 

  7. Bokisch VA, Muller-Eberhard HJ. Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase. J Clin Invest. 1970;49:2427–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006;119:267–74.

    PubMed  Google Scholar 

  9. Botto M, Kirschfink M, Macor P, Pickering MC, Wurzner R, Tedesco F. Complement in human diseases: lessons from complement deficiencies. Mol Immunol. 2009;46:2774–83.

    CAS  PubMed  Google Scholar 

  10. Brandtzaeg P, Mollnes TE, Kierulf P. Complement activation and endotoxin levels in systemic meningococcal disease. J Infect Dis. 1989;160:58–65.

    CAS  PubMed  Google Scholar 

  11. Buckley RH. Immunoglobulin G subclass deficiency: fact or fancy? Curr Allergy Asthma Rep. 2002;2:356–60.

    PubMed  Google Scholar 

  12. Cao H, Hegele RA. DNA polymorphism and mutations in CPN1, including the genomic basis of carboxypeptidase N deficiency. J Hum Genet. 2003;48:20–2.

    CAS  PubMed  Google Scholar 

  13. Carlsson M, Sjoholm AG, Eriksson L, Thiel S, Jensenius JC, Segelmark M, Truedsson L. Deficiency of the mannan-binding lectin pathway of complement and poor outcome in cystic fibrosis: bacterial colonization may be decisive for a relationship. Clin Exp Immunol. 2005;139:306–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Cole DS, Morgan BP. Beyond lysis: how complement influences cell fate. Clin Sci (Lond). 2003;104:455–66.

    CAS  Google Scholar 

  15. Colten HR, Rosen FS. Complement deficiencies. Annu Rev Immunol. 1992;10:809–34.

    CAS  PubMed  Google Scholar 

  16. Cornacoff JB, Hebert LA, Smead WL, VanAman ME, Birmingham DJ, Waxman FJ. Primate erythrocyte-immune complex-clearing mechanism. J Clin Invest. 1983;71:236–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009;15:69–78.

    CAS  PubMed  Google Scholar 

  18. Davis 3rd AE. Hereditary angioedema: a current state-of-the-art review, III: mechanisms of hereditary angioedema. Ann Allergy Asthma Immunol. 2008;100:S7–12.

    CAS  PubMed  Google Scholar 

  19. Davis 3rd AE, Harrison RA, Lachmann PJ. Physiologic inactivation of fluid phase C3b: isolation and structural analysis of C3c, C3d, g (alpha 2D), and C3g. J Immunol. 1984;132:1960–6.

    CAS  PubMed  Google Scholar 

  20. Davis 3rd AE, Mejia P, Lu F. Biological activities of C1 inhibitor. Mol Immunol. 2008;45:4057–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. de Cordoba SR, de Jorge EG. Translational mini-review series on complement factor H: genetics and disease associations of human complement factor H. Clin Exp Immunol. 2008;151:1–13.

    PubMed  PubMed Central  Google Scholar 

  22. Degn SE, Jensenius JC, Thiel S. Disease-causing mutations in genes of the complement system. Am J Hum Genet. 2011;88:689–705.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Dempsey PW, Allison ME, Akkaraju S, Goodnow CC, Fearon DT. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science. 1996;271:348–50.

    CAS  PubMed  Google Scholar 

  24. Dommett RM, Klein N, Turner MW. Mannose-binding lectin in innate immunity: past, present and future. Tissue Antigens. 2006;68:193–209.

    CAS  PubMed  Google Scholar 

  25. Endo Y, Matsushita M, Fujita T. The role of ficolins in the lectin pathway of innate immunity. Int J Biochem Cell Biol. 2011;43:705–12.

    CAS  PubMed  Google Scholar 

  26. Fearon DT, Austen KF. Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. J Exp Med. 1975;142:856–63.

    CAS  PubMed  Google Scholar 

  27. Fearon DT, Austen KF, Ruddy S. Formation of a hemolytically active cellular intermediate by the interaction between properdin factors B and D and the activated third component of complement. J Exp Med. 1973;138:1305–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Figueroa J, Andreoni J, Densen P. Complement deficiency states and meningococcal disease. Immunol Res. 1993;12:295–311.

    CAS  PubMed  Google Scholar 

  29. Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev. 1991;4:359–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Fijen CA, Kuijper EJ, Dankert J, Daha MR, Caugant DA. Characterization of Neisseria meningitidis strains causing disease in complement-deficient and complement-sufficient patients. J Clin Microbiol. 1998;36:2342–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Fijen CA, Kuijper EJ, te Bulte MT, Daha MR, Dankert J. Assessment of complement deficiency in patients with meningococcal disease in The Netherlands. Clin Infect Dis. 1999;28:98–105.

    CAS  PubMed  Google Scholar 

  32. Fijen CA, van den Bogaard R, Schipper M, Mannens M, Schlesinger M, Nordin FG, Dankert J, Daha MR, Sjoholm AG, Truedsson L, Kuijper EJ. Properdin deficiency: molecular basis and disease association. Mol Immunol. 1999;36:863–7.

    CAS  PubMed  Google Scholar 

  33. Forneris F, Ricklin D, Wu J, Tzekou A, Wallace RS, Lambris JD, Gros P. Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science. 2010;330:1816–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Frank MM. Hereditary angioedema: the clinical syndrome and its management in the United States. Immunol Allergy Clin North Am. 2006;26:653–68.

    PubMed  Google Scholar 

  35. Frank MM, Fries LF. The role of complement in inflammation and phagocytosis. Immunol Today. 1991;12:322–6.

    CAS  PubMed  Google Scholar 

  36. Fukumori Y, Yoshimura K, Ohnoki S, Yamaguchi H, Akagaki Y, Inai S. A high incidence of C9 deficiency among healthy blood donors in Osaka, Japan. Int Immunol. 1989;1:85–9.

    CAS  PubMed  Google Scholar 

  37. Garcia-Laorden MI, Sole-Violan J, de Castro F R, Aspa J, Briones ML, Garcia-Saavedra A, Rajas O, Blanquer J, Caballero-Hidalgo A, Marcos-Ramos JA, Hernandez-Lopez J, Rodriguez-Gallego C. Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults. J Allergy Clin Immunol. 2008;122:368–74, 374 e361–362.

    CAS  PubMed  Google Scholar 

  38. Garlatti V, Chouquet A, Lunardi T, Vives R, Paidassi H, Lortat-Jacob H, Thielens NM, Arlaud GJ, Gaboriaud C. Cutting edge: C1q binds deoxyribose and heparan sulfate through neighboring sites of its recognition domain. J Immunol. 2010;185:808–12.

    CAS  PubMed  Google Scholar 

  39. Garred P, Larsen F, Madsen HO, Koch C. Mannose-binding lectin deficiency--revisited. Mol Immunol. 2003;40:73–84.

    CAS  PubMed  Google Scholar 

  40. Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO. Mannose-binding lectin and its genetic variants. Genes Immun. 2006;7:85–94.

    CAS  PubMed  Google Scholar 

  41. Garred P, Madsen HO, Marquart H, Hansen TM, Sorensen SF, Petersen J, Volck B, Svejgaard A, Graudal NA, Rudd PM, Dwek RA, Sim RB, Andersen V. Two edged role of mannose binding lectin in rheumatoid arthritis: a cross sectional study. J Rheumatol. 2000;27:26–34.

    CAS  PubMed  Google Scholar 

  42. Garred P, Pressler T, Madsen HO, Frederiksen B, Svejgaard A, Hoiby N, Schwartz M, Koch C. Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest. 1999;104:431–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Ghebrehiwet B, Silverberg M, Kaplan AP. Activation of the classical pathway of complement by Hageman factor fragment. J Exp Med. 1981;153:665–76.

    CAS  PubMed  Google Scholar 

  44. Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Arranz EA, Garrido CA, Lopez-Trascasa M, Sanchez-Corral P, Morgan BP, Rodriguez de Cordoba S. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2007;104:240–5.

    CAS  PubMed  Google Scholar 

  45. Gompels MM, Lock RJ. C1 inhibitor deficiency: diagnosis. Clin Exp Dermatol. 2005;30:460–2.

    CAS  PubMed  Google Scholar 

  46. Gompels MM, Lock RJ, Abinun M, Bethune CA, Davies G, Grattan C, Fay AC, Longhurst HJ, Morrison L, Price A, Price M, Watters D. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005;139:379–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Goonewardena P, Sjoholm AG, Nilsson LA, Pettersson U. Linkage analysis of the properdin deficiency gene: suggestion of a locus in the proximal part of the short arm of the X chromosome. Genomics. 1988;2:115–8.

    CAS  PubMed  Google Scholar 

  48. Gordon DL, Kaufman RM, Blackmore TK, Kwong J, Lublin DM. Identification of complement regulatory domains in human factor H. J Immunol. 1995;155:348–56.

    CAS  PubMed  Google Scholar 

  49. Gros P, Milder FJ, Janssen BJ. Complement driven by conformational changes. Nat Rev Immunol. 2008;8:48–58.

    CAS  PubMed  Google Scholar 

  50. Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med. 2009;360:544–6.

    CAS  PubMed  Google Scholar 

  51. Hadders MA, Beringer DX, Gros P. Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. Science. 2007;317:1552–4.

    CAS  PubMed  Google Scholar 

  52. Hajishengallis G, Lambris JD. Crosstalk pathways between Toll-like receptors and the complement system. Trends Immunol. 2010;31:154–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Hamad OA, Ekdahl KN, Nilsson PH, Andersson J, Magotti P, Lambris JD, Nilsson B. Complement activation triggered by chondroitin sulfate released by thrombin receptor-activated platelets. J Thromb Haemost. 2008;6:1413–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Hansen S, Selman L, Palaniyar N, Ziegler K, Brandt J, Kliem A, Jonasson M, Skjoedt MO, Nielsen O, Hartshorn K, Jorgensen TJ, Skjodt K, Holmskov U. Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. J Immunol. 2010;185:6096–104.

    CAS  PubMed  Google Scholar 

  55. Harboe M, Ulvund G, Vien L, Fung M, Mollnes TE. The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation. Clin Exp Immunol. 2004;138:439–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Heja D, Kocsis A, Dobo J, Szilagyi K, Szasz R, Zavodszky P, Pal G, Gal P. Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2. Proc Natl Acad Sci U S A. 2012;109:10498–503.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Hellemann D, Larsson A, Madsen HO, Bonde J, Jarlov JO, Wiis J, Faber T, Wetterslev J, Garred P. Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients. Hum Mol Genet. 2007;16:3071–80.

    CAS  PubMed  Google Scholar 

  58. Henriksen ML, Brandt J, Iyer SS, Thielens NM, Hansen S. Characterization of the interaction between collectin 11 (CL-11, CL-K1) and nucleic acids. Mol Immunol. 2013;56:757–67.

    CAS  PubMed  Google Scholar 

  59. Hiemstra PS, Langeler E, Compier B, Keepers Y, Leijh PC, van den Barselaar MT, Overbosch D, Daha MR. Complete and partial deficiencies of complement factor D in a Dutch family. J Clin Invest. 1989;84:1957–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, Roth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233–43.

    CAS  PubMed  Google Scholar 

  61. Hochsmann B, Schrezenmeier H. Congenital CD59 deficiency. Hematol Oncol Clin North Am. 2015;29:495–507.

    PubMed  Google Scholar 

  62. Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, Lambris JD, Warner RL, Flierl MA, Hoesel LM, Gebhard F, Younger JG, Drouin SM, Wetsel RA, Ward PA. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med. 2006;12:682–7.

    CAS  PubMed  Google Scholar 

  63. Hugli TE. Biochemistry and biology of anaphylatoxins. Complement. 1986;3:111–27.

    CAS  PubMed  Google Scholar 

  64. Inai S, Akagaki Y, Moriyama T, Fukumori Y, Yoshimura K, Ohnoki S, Yamaguchi H. Inherited deficiencies of the late-acting complement components other than C9 found among healthy blood donors. Int Arch Allergy Appl Immunol. 1989;90:274–9.

    CAS  PubMed  Google Scholar 

  65. Jalanko H, Peltonen S, Koskinen A, Puntila J, Isoniemi H, Holmberg C, Pinomaki A, Armstrong E, Koivusalo A, Tukiainen E, Makisalo H, Saland J, Remuzzi G, de Cordoba S, Lassila R, Meri S, Jokiranta TS. Successful liver-kidney transplantation in two children with aHUS caused by a mutation in complement factor H. Am J Transplant. 2008;8:216–21.

    CAS  PubMed  Google Scholar 

  66. Janssen BJ, Huizinga EG, Raaijmakers HC, Roos A, Daha MR, Nilsson-Ekdahl K, Nilsson B, Gros P. Structures of complement component C3 provide insights into the function and evolution of immunity. Nature. 2005;437:505–11.

    CAS  PubMed  Google Scholar 

  67. Johnson CA, Densen P, Wetsel RA, Cole FS, Goeken NE, Colten HR. Molecular heterogeneity of C2 deficiency. N Engl J Med. 1992;326:871–4.

    CAS  PubMed  Google Scholar 

  68. Jonsson G, Truedsson L, Sturfelt G, Oxelius VA, Braconier JH, Sjoholm AG. Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. Medicine (Baltimore). 2005;84:23–34.

    Google Scholar 

  69. Jozsi M, Licht C, Strobel S, Zipfel SL, Richter H, Heinen S, Zipfel PF, Skerka C. Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 2008;111:1512–4.

    CAS  PubMed  Google Scholar 

  70. Kajander T, Lehtinen MJ, Hyvarinen S, Bhattacharjee A, Leung E, Isenman DE, Meri S, Goldman A, Jokiranta TS. Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement. Proc Natl Acad Sci U S A. 2011;108:2897–902.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Kaplan AP. C1 inhibitor deficiency: hereditary and acquired forms. J Investig Allergol Clin Immunol. 2001;11:211–9.

    CAS  PubMed  Google Scholar 

  72. Kaplan AP, Greaves MW. Angioedema. J Am Acad Dermatol. 2005;53:373–88; quiz 389–392.

    PubMed  Google Scholar 

  73. Kavanagh D, Goodship TH, Richards A. Atypical haemolytic uraemic syndrome. Br Med Bull. 2006;77–78:5–22.

    PubMed  Google Scholar 

  74. Kemper C, Kohl J. Novel roles for complement receptors in T cell regulation and beyond. Mol Immunol. 2013;56:181–90.

    CAS  PubMed  Google Scholar 

  75. Kilpatrick DC. Mannan-binding lectin: clinical significance and applications. Biochim Biophys Acta. 2002;1572:401–13.

    CAS  PubMed  Google Scholar 

  76. Kimura Y, Miwa T, Zhou L, Song WC. Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement. Blood. 2008;111:732–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Kishore U, Reid KB. C1q: structure, function, and receptors. Immunopharmacology. 2000;49:159–70.

    CAS  PubMed  Google Scholar 

  78. Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Kohl J. The role of the anaphylatoxins in health and disease. Mol Immunol. 2009;46:2753–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Kovarik J, Siegrist CA. Immunity in early life. Immunol Today. 1998;19:150–2.

    CAS  PubMed  Google Scholar 

  80. Krawitz PM, Hochsmann B, Murakami Y, Teubner B, Kruger U, Klopocki E, Neitzel H, Hoellein A, Schneider C, Parkhomchuk D, Hecht J, Robinson PN, Mundlos S, Kinoshita T, Schrezenmeier H. A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT. Blood. 2013;122:1312–5.

    CAS  PubMed  Google Scholar 

  81. Lachmann P. Complement before molecular biology. Mol Immunol. 2006;43:496–508.

    CAS  PubMed  Google Scholar 

  82. Lachmann PJ. The amplification loop of the complement pathways. Adv Immunol. 2009;104:115–49.

    CAS  PubMed  Google Scholar 

  83. Lachmann PJ, Nicol P. Reaction mechanism of the alternative pathway of complement fixation. Lancet. 1973;1:465–7.

    CAS  PubMed  Google Scholar 

  84. Lambris JD, Ricklin D, Geisbrecht BV. Complement evasion by human pathogens. Nat Rev Microbiol. 2008;6:132–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Le Friec G, Kemper C. Complement: coming full circle. Arch Immunol Ther Exp (Warsz). 2009;57:393–407.

    Google Scholar 

  86. Levy Y, George J, Yona E, Shoenfeld Y. Partial lipodystrophy, mesangiocapillary glomerulonephritis, and complement dysregulation. An autoimmune phenomenon. Immunol Res. 1998;18:55–60.

    CAS  PubMed  Google Scholar 

  87. Lipscombe RJ, Sumiya M, Hill AV, Lau YL, Levinsky RJ, Summerfield JA, Turner MW. High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Hum Mol Genet. 1992;1:709–15.

    CAS  PubMed  Google Scholar 

  88. Lipsker D, Hauptmann G. Cutaneous manifestations of complement deficiencies. Lupus. 2010;19:1096–106.

    CAS  PubMed  Google Scholar 

  89. Longhi MP, Harris CL, Morgan BP, Gallimore A. Holding T cells in check – a new role for complement regulators? Trends Immunol. 2006;27:102–8.

    CAS  PubMed  Google Scholar 

  90. Ma YJ, Skjoedt MO, Garred P. Collectin-11/MASP complex formation triggers activation of the lectin complement pathway – the fifth lectin pathway initiation complex. J Innate Immun. 2013;5:242–50.

    CAS  PubMed  Google Scholar 

  91. Madsen HO, Garred P, Kurtzhals JA, Lamm LU, Ryder LP, Thiel S, Svejgaard A. A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein. Immunogenetics. 1994;40:37–44.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  93. Markiewski MM, DeAngelis RA, Strey CW, Foukas PG, Gerard C, Gerard N, Wetsel RA, Lambris JD. The regulation of liver cell survival by complement. J Immunol. 2009;182:5412–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD. Complement and coagulation: strangers or partners in crime? Trends Immunol. 2007;28:184–92.

    CAS  PubMed  Google Scholar 

  95. Markovic SN, Inwards DJ, Frigas EA, Phyliky RP. Acquired C1 esterase inhibitor deficiency. Ann Intern Med. 2000;132:144–50.

    CAS  PubMed  Google Scholar 

  96. Mathews KP, Pan PM, Gardner NJ, Hugli TE. Familial carboxypeptidase N deficiency. Ann Intern Med. 1980;93:443–5.

    CAS  PubMed  Google Scholar 

  97. Moldovan D, Bernstein JA, Cicardi M. Recombinant replacement therapy for hereditary angioedema due to C1 inhibitor deficiency. Immunotherapy. 2015;7:739–52.

    CAS  PubMed  Google Scholar 

  98. Mollnes TE, Brekke OL, Fung M, Fure H, Christiansen D, Bergseth G, Videm V, Lappegard KT, Kohl J, Lambris JD. Essential role of the C5a receptor in E coli-induced oxidative burst and phagocytosis revealed by a novel lepirudin-based human whole blood model of inflammation. Blood. 2002;100:1869–77.

    CAS  PubMed  Google Scholar 

  99. Mollnes TE, Song WC, Lambris JD. Complement in inflammatory tissue damage and disease. Trends Immunol. 2002;23:61–4.

    CAS  PubMed  Google Scholar 

  100. Morgan BP, Gasque P. Extrahepatic complement biosynthesis: where, when and why? Clin Exp Immunol. 1997;107:1–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Munthe-Fog L, Hummelshoj T, Honore C, Madsen HO, Permin H, Garred P. Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency. N Engl J Med. 2009;360:2637–44.

    CAS  PubMed  Google Scholar 

  102. Munthe-Fog L, Hummelshoj T, Ma YJ, Hansen BE, Koch C, Madsen HO, Skjodt K, Garred P. Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state. Mol Immunol. 2008;45:2660–6.

    CAS  PubMed  Google Scholar 

  103. Nauta AJ, Castellano G, Xu W, Woltman AM, Borrias MC, Daha MR, van Kooten C, Roos A. Opsonization with C1q and mannose-binding lectin targets apoptotic cells to dendritic cells. J Immunol. 2004;173:3044–50.

    CAS  PubMed  Google Scholar 

  104. Nilsson B, Ekdahl KN. Complement diagnostics: concepts, indications, and practical guidelines. Clin Dev Immunol. 2012;2012:962702.

    PubMed  PubMed Central  Google Scholar 

  105. Ohlenschlaeger T, Garred P, Madsen HO, Jacobsen S. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med. 2004;351:260–7.

    CAS  PubMed  Google Scholar 

  106. Olesen HV, Jensenius JC, Steffensen R, Thiel S, Schiotz PO. The mannan-binding lectin pathway and lung disease in cystic fibrosis--disfunction of mannan-binding lectin-associated serine protease 2 (MASP-2) may be a major modifier. Clin Immunol. 2006;121:324–31.

    CAS  PubMed  Google Scholar 

  107. Olsson RF, Hagelberg S, Schiller B, Ringden O, Truedsson L, Ahlin A. Allogeneic hematopoietic stem cell transplantation in the treatment of human C1q deficiency: the karolinska experience. Transplantation. 2015;100(6):1356–62.

    Google Scholar 

  108. Paidassi H, Tacnet-Delorme P, Garlatti V, Darnault C, Ghebrehiwet B, Gaboriaud C, Arlaud GJ, Frachet P. C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition. J Immunol. 2008;180:2329–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Paidassi H, Tacnet-Delorme P, Lunardi T, Arlaud GJ, Thielens NM, Frachet P. The lectin-like activity of human C1q and its implication in DNA and apoptotic cell recognition. FEBS Lett. 2008;582:3111–6.

    CAS  PubMed  Google Scholar 

  110. Pangburn MK, Muller-Eberhard HJ. Initiation of the alternative complement pathway due to spontaneous hydrolysis of the thioester of C3. Ann N Y Acad Sci. 1983;421:291–8.

    CAS  PubMed  Google Scholar 

  111. Perkins SJ, Nealis AS, Sutton BJ, Feinstein A. Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation. J Mol Biol. 1991;221:1345–66.

    CAS  PubMed  Google Scholar 

  112. Petersen SV, Thiel S, Jensen L, Steffensen R, Jensenius JC. An assay for the mannan-binding lectin pathway of complement activation. J Immunol Methods. 2001;257:107–16.

    CAS  PubMed  Google Scholar 

  113. Pettigrew HD, Teuber SS, Gershwin ME. Clinical significance of complement deficiencies. Ann N Y Acad Sci. 2009;1173:108–23.

    CAS  PubMed  Google Scholar 

  114. Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol. 2000;76:227–324.

    CAS  PubMed  Google Scholar 

  115. Platts-Mills TA, Ishizaka K. Activation of the alternate pathway of human complements by rabbit cells. J Immunol. 1974;113:348–58.

    CAS  PubMed  Google Scholar 

  116. Ram S, Lewis LA, Rice PA. Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev. 2010;23:740–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Remuzzi G, Ruggenenti P, Colledan M, Gridelli B, Bertani A, Bettinaglio P, Bucchioni S, Sonzogni A, Bonanomi E, Sonzogni V, Platt JL, Perico N, Noris M. Hemolytic uremic syndrome: a fatal outcome after kidney and liver transplantation performed to correct factor h gene mutation. Am J Transplant. 2005;5:1146–50.

    PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA, Leal GF, Dallapiccola B, Carnevale F, Bitner-Glindzicz M, Lees M, Hennekam R, Stanier P, Burns AJ, Peeters H, Alkuraya FS, Beales PL. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet. 2011;43:197–203.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Ross SC, Densen P. Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore). 1984;63:243–73.

    CAS  Google Scholar 

  121. Rugonfalvi-Kiss S, Endresz V, Madsen HO, Burian K, Duba J, Prohaszka Z, Karadi I, Romics L, Gonczol E, Fust G, Garred P. Association of Chlamydia pneumoniae with coronary artery disease and its progression is dependent on the modifying effect of mannose-binding lectin. Circulation. 2002;106:1071–6.

    CAS  PubMed  Google Scholar 

  122. Sahu A, Lambris JD. Structure and biology of complement protein C3, a connecting link between innate and acquired immunity. Immunol Rev. 2001;180:35–48.

    CAS  PubMed  Google Scholar 

  123. Saland JM, Emre SH, Shneider BL, Benchimol C, Ames S, Bromberg JS, Remuzzi G, Strain L, Goodship TH. Favorable long-term outcome after liver-kidney transplant for recurrent hemolytic uremic syndrome associated with a factor H mutation. Am J Transplant. 2006;6:1948–52.

    CAS  PubMed  Google Scholar 

  124. Sallenbach S, Thiel S, Aebi C, Otth M, Bigler S, Jensenius JC, Schlapbach LJ, Ammann RA. Serum concentrations of lectin-pathway components in healthy neonates, children and adults: mannan-binding lectin (MBL), M-, L-, and H-ficolin, and MBL-associated serine protease-2 (MASP-2). Pediatr Allergy Immunol. 2011;22:424–30.

    PubMed  Google Scholar 

  125. Samano ES, Ribeiro Lde M, Gorescu RG, Rocha KC, Grumach AS. Involvement of C4 allotypes in the pathogenesis of human diseases. Rev Hosp Clin Fac Med Sao Paulo. 2004;59:138–44.

    PubMed  Google Scholar 

  126. Schejbel L, Skattum L, Hagelberg S, Ahlin A, Schiller B, Berg S, Genel F, Truedsson L, Garred P. Molecular basis of hereditary C1q deficiency--revisited: identification of several novel disease-causing mutations. Genes Immun. 2011;12:626–34.

    CAS  PubMed  Google Scholar 

  127. Schlapbach LJ, Thiel S, Kessler U, Ammann RA, Aebi C, Jensenius JC. Congenital H-ficolin deficiency in premature infants with severe necrotising enterocolitis. Gut. 2011;60:1438–9.

    PubMed  Google Scholar 

  128. Schmidtko J, Peine S, El-Housseini Y, Pascual M, Meier P. Treatment of atypical hemolytic uremic syndrome and thrombotic microangiopathies: a focus on eculizumab. Am J Kidney Dis. 2013;61:289–99.

    CAS  PubMed  Google Scholar 

  129. Seelen MA, Roos A, Wieslander J, Mollnes TE, Sjoholm AG, Wurzner R, Loos M, Tedesco F, Sim RB, Garred P, Alexopoulos E, Turner MW, Daha MR. Functional analysis of the classical, alternative, and MBL pathways of the complement system: standardization and validation of a simple ELISA. J Immunol Methods. 2005;296:187–98.

    CAS  PubMed  Google Scholar 

  130. Sim RB, Arlaud GJ, Colomb MG. C1 inhibitor-dependent dissociation of human complement component C1 bound to immune complexes. Biochem J. 1979;179:449–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Sim RB, Kishore U, Villiers CL, Marche PN, Mitchell DA. C1q binding and complement activation by prions and amyloids. Immunobiology. 2007;212:355–62.

    CAS  PubMed  Google Scholar 

  132. Sim TC, Grant JA. Hereditary angioedema: its diagnostic and management perspectives. Am J Med. 1990;88:656–64.

    CAS  PubMed  Google Scholar 

  133. Sinclair D, Smith A, Cranfield T, Lock RJ. Acquired C1 esterase inhibitor deficiency or serendipity? The chance finding of a paraprotein after an apparently low C1 esterase inhibitor concentration. J Clin Pathol. 2004;57:445–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Sirmaci A, Walsh T, Akay H, Spiliopoulos M, Sakalar YB, Hasanefendioglu-Bayrak A, Duman D, Farooq A, King MC, Tekin M. MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of Carnevale, Malpuech, OSA, and Michels syndromes. Am J Hum Genet. 2010;87:679–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Sjoholm AG. Inherited complement deficiency states: implications for immunity and immunological disease. APMIS. 1990;98:861–74.

    CAS  PubMed  Google Scholar 

  136. Sjoholm AG, Jonsson G, Braconier JH, Sturfelt G, Truedsson L. Complement deficiency and disease: an update. Mol Immunol. 2006;43:78–85.

    CAS  PubMed  Google Scholar 

  137. Skattum L, van Deuren M, van der Poll T, Truedsson L. Complement deficiency states and associated infections. Mol Immunol. 2011;48:1643–55.

    CAS  PubMed  Google Scholar 

  138. Skerka C, Chen Q, Fremeaux-Bacchi V, Roumenina LT. Complement factor H related proteins (CFHRs). Mol Immunol. 2013;56:170–80.

    CAS  PubMed  Google Scholar 

  139. Spitzer D, Mitchell LM, Atkinson JP, Hourcade DE. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J Immunol. 2007;179:2600–8.

    CAS  PubMed  Google Scholar 

  140. Sprong T, Roos D, Weemaes C, Neeleman C, Geesing CL, Mollnes TE, van Deuren M. Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood. 2006;107:4865–70.

    CAS  PubMed  Google Scholar 

  141. Stegert M, Bock M, Trendelenburg M. Clinical presentation of human C1q deficiency: How much of a lupus? Mol Immunol. 2015;67:3–11.

    CAS  PubMed  Google Scholar 

  142. Stengaard-Pedersen K, Thiel S, Gadjeva M, Moller-Kristensen M, Sorensen R, Jensen LT, Sjoholm AG, Fugger L, Jensenius JC. Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med. 2003;349:554–60.

    CAS  PubMed  Google Scholar 

  143. Stephan AH, Barres BA, Stevens B. The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci. 2012;35:369–89.

    CAS  PubMed  Google Scholar 

  144. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, Micheva KD, Mehalow AK, Huberman AD, Stafford B, Sher A, Litke AM, Lambris JD, Smith SJ, John SW, Barres BA. The classical complement cascade mediates CNS synapse elimination. Cell. 2007;131:1164–78.

    CAS  PubMed  Google Scholar 

  145. Strey CW, Markiewski M, Mastellos D, Tudoran R, Spruce LA, Greenbaum LE, Lambris JD. The proinflammatory mediators C3a and C5a are essential for liver regeneration. J Exp Med. 2003;198:913–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Sullivan KE, Petri MA, Schmeckpeper BJ, McLean RH, Winkelstein JA. Prevalence of a mutation causing C2 deficiency in systemic lupus erythematosus. J Rheumatol. 1994;21:1128–33.

    CAS  PubMed  Google Scholar 

  147. Sumiya M, Super M, Tabona P, Levinsky RJ, Arai T, Turner MW, Summerfield JA. Molecular basis of opsonic defect in immunodeficient children. Lancet. 1991;337:1569–70.

    CAS  PubMed  Google Scholar 

  148. Takeda J, Miyata T, Kawagoe K, Iida Y, Endo Y, Fujita T, Takahashi M, Kitani T, Kinoshita T. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993;73:703–11.

    CAS  PubMed  Google Scholar 

  149. Tarailo-Graovac M, Sinclair G, Stockler-Ipsiroglu S, Van Allen M, Rozmus J, Shyr C, Biancheri R, Oh T, Sayson B, Lafek M, Ross CJ, Robinson WP, Wasserman WW, Rossi A, van Karnebeek CD. The genotypic and phenotypic spectrum of PIGA deficiency. Orphanet J Rare Dis. 2015;10:23.

    PubMed  PubMed Central  Google Scholar 

  150. Tegla CA, Cudrici C, Patel S, Trippe 3rd R, Rus V, Niculescu F, Rus H. Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res. 2011;51:45–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Thiel S. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Mol Immunol. 2007;44:3875–88.

    CAS  PubMed  Google Scholar 

  152. Thiel S, Frederiksen PD, Jensenius JC. Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol. 2006;43:86–96.

    CAS  PubMed  Google Scholar 

  153. Thiel S, Steffensen R, Christensen IJ, Ip WK, Lau YL, Reason IJ, Eiberg H, Gadjeva M, Ruseva M, Jensenius JC. Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun. 2007;8:154–63.

    CAS  PubMed  Google Scholar 

  154. Titomanlio L, Bennaceur S, Bremond-Gignac D, Baumann C, Dupuy O, Verloes A. Michels syndrome, Carnevale syndrome, OSA syndrome, and Malpuech syndrome: variable expression of a single disorder (3MC syndrome)? Am J Med Genet A. 2005;137A:332–5.

    PubMed  Google Scholar 

  155. Trouw LA, Blom AM, Gasque P. Role of complement and complement regulators in the removal of apoptotic cells. Mol Immunol. 2008;45:1199–207.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  157. Usami M, Mitsunaga K, Miyajima A, Sunouchi M, Doi O. Complement component C3 functions as an embryotrophic factor in early postimplantation rat embryos. Int J Dev Biol. 2010;54:1277–85.

    CAS  PubMed  Google Scholar 

  158. Valdimarsson H, Vikingsdottir T, Bang P, Saevarsdottir S, Gudjonsson JE, Oskarsson O, Christiansen M, Blou L, Laursen I, Koch C. Human plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic study. Scand J Immunol. 2004;59:97–102.

    CAS  PubMed  Google Scholar 

  159. Walport MJ. Complement. First of two parts. N Engl J Med. 2001;344:1058–66.

    CAS  PubMed  Google Scholar 

  160. Walport MJ. Complement. Second of two parts. N Engl J Med. 2001;344:1140–4.

    CAS  PubMed  Google Scholar 

  161. Waters AM, Licht C. aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol. 2011;26:41–57.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  163. Witzel-Schlomp K, Spath PJ, Hobart MJ, Fernie BA, Rittner C, Kaufmann T, Schneider PM. The human complement C9 gene: identification of two mutations causing deficiency and revision of the gene structure. J Immunol. 1997;158:5043–9.

    CAS  PubMed  Google Scholar 

  164. Wurzner R, Orren A, Lachmann PJ. Inherited deficiencies of the terminal components of human complement. Immunodefic Rev. 1992;3:123–47.

    CAS  PubMed  Google Scholar 

  165. Yamada M, Oritani K, Kaisho T, Ishikawa J, Yoshida H, Takahashi I, Kawamoto S, Ishida N, Ujiie H, Masaie H, Botto M, Tomiyama Y, Matsuzawa Y. Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells. Eur J Immunol. 2004;34:221–30.

    CAS  PubMed  Google Scholar 

  166. Zarkadis IK, Mastellos D, Lambris JD. Phylogenetic aspects of the complement system. Dev Comp Immunol. 2001;25:745–62.

    CAS  PubMed  Google Scholar 

  167. Zhang X, Kimura Y, Fang C, Zhou L, Sfyroera G, Lambris JD, Wetsel RA, Miwa T, Song WC. Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo. Blood. 2007;110:228–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Ziccardi RJ, Cooper NR. Active disassembly of the first complement component, C-1, by C-1 inactivator. J Immunol. 1979;123:788–92.

    CAS  PubMed  Google Scholar 

  169. Ziccardi RJ, Tschopp J. The dissociation properties of native C1. Biochem Biophys Res Commun. 1982;107:618–23.

    CAS  PubMed  Google Scholar 

  170. Zipfel PF, Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol. 2009;9:729–40.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Nutrition, School of Nutrition and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Mahmoudi MD, PhD

  2. Dietitians and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Maryam Mahmoudi MD, PhD

  3. Department of Immunology, Oslo University Hospital, Oslo, Norway

    Per H. Nilsson PhD & Tom Eirik Mollnes MD, PhD

  4. K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway

    Per H. Nilsson PhD & Tom Eirik Mollnes MD, PhD

  5. Research Laboratory, Nordland Hospital, Bodø, Norway

    Tom Eirik Mollnes MD, PhD

  6. Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway

    Tom Eirik Mollnes MD, PhD

  7. Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway

    Tom Eirik Mollnes MD, PhD

  8. Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Dirk Roos PhD

  9. Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Kathleen E. Sullivan MD, PhD

Authors
  1. Maryam Mahmoudi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Per H. Nilsson PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tom Eirik Mollnes MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dirk Roos PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathleen E. Sullivan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Research Center for Immunodeficiencies, Children's Medical Center Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

  2. Department of Immunology and Biology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Asghar Aghamohammadi

  3. Division of Immunology, Boston Children's Hospital Harvard Medical School, Boston, Massachusetts, USA

    Luigi D. Notarangelo

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Mahmoudi, M., Nilsson, P.H., Mollnes, T.E., Roos, D., Sullivan, K.E. (2017). Complement Deficiencies. In: Rezaei, N., Aghamohammadi, A., Notarangelo, L. (eds) Primary Immunodeficiency Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-52909-6_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-52909-6_8

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-52907-2

  • Online ISBN: 978-3-662-52909-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation