Chapter 77 : Hereditary and Acquired Complement Deficiencies

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Hereditary and Acquired Complement Deficiencies, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818722/9781555818715_CH77-1.gif /docserver/preview/fulltext/10.1128/9781555818722/9781555818715_CH77-2.gif


Complement deficiencies comprise a small but important category of primary immune deficiency diseases. Complement deficiency states can also be acquired from activation or inhibition of the complement system, temporarily depleting components faster than they can be replaced or causing changes in control of the system. Complement plays an important role in the host's response to infection by directly killing bacteria, neutralizing viruses, or coating microbial surfaces with complement fragments that enhance uptake and killing by phagocytes, a process called opsonization that ensures that objects identified as foreign by complement are dealt with quickly and efficiently. Complement serves as a link between many of the activities of acquired immunity, with ties to diverse cell signal responses and other defense mechanisms, as an ever-increasing number of related conditions are identified (1).

Citation: Giclas P. 2016. Hereditary and Acquired Complement Deficiencies, p 749-765. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch77
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Complement was one of the earliest members of the innate immune system to evolve, and, as such, different forms of pattern recognition allowed it to become active against a variety of organisms and substances without the need for prior exposure. The three boxes to the left (classical pathway [CP], blue; lectin pathway [LP], orange; alternative pathway [AP], red) indicate examples of one of the triggers for activation of each pathway. As drawn, the C3 molecule is the central target for all three pathways. Activation of the CP by immune complexes, or the LP by a recognized target pattern, results in cleavage of C3, C4, and C2. Clearance of the complex or LP target from the circulation occurs through interaction of the phagocytes in the liver and spleen with the C4b and C3b bound to the complex. The alternative pathway is different. In the AP, the unique protein properdin allows the formation of an amplification process (shown as circle of arrows) in which a very large amount of C3 but not C4 becomes rapidly cleaved. The resulting C3b from this process becomes covalently bound to the surface of nearby proteins, microbes, and cells and flags them as targets for destruction by the immune system. The fragments of C3 and C4 form the major opsonins that are used by cells such as phagocytes and lymphocytes to clear the C3 and C4 fragments. Note that complement fragments can be useful in the laboratory to identify the pathway involved in a reaction. Note also that a large decrease in serum C3 but not C4 is indicative of AP activation. The majority of the physiological effects of complement activation are due to the inflammatory properties of the fragments. These include opsonization, chemotaxis, mediator release, priming of phagocytes and lymphocytes, apoptosis, and direct killing of microbes by lysis.

Citation: Giclas P. 2016. Hereditary and Acquired Complement Deficiencies, p 749-765. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch77
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ricklin D, Lambris JD . 2013. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol 190 : 3831 3838.[CrossRef].[PubMed]
2. Giclas PC, . 1997. Complement tests, p 181 186. In Rose NR, Conway de Macario E, Folds JD, Lane HC, Nakamura RM (ed), Manual of Clinical Laboratory Immunology, 5th ed. ASM Press, Washington, DC.
3. Giclas PC . 2001. Classical pathway evaluation. Curr Protoc Immunol Chapter 13 :Unit 13.1. doi:10.1002/0471142735.im1301s09.[CrossRef] http://dx.doi.org/doi:10.1002/0471142735.im1301s09
4. Giclas PC . 2001. Alternative pathway evaluation. Curr Protoc Immunol Chapter 13 :Unit 13.2. doi:10.1002/0471142735.im1302s09.[CrossRef] http://dx.doi.org/doi:10.1002/0471142735.im1302s09
5. Giclas PC, . 2002. Choosing complement tests: differentiating between hereditary and acquired deficiency, p 111 116. In Rose NR, Hamilton RG, Detrick B (ed) Manual of Clinical Laboratory Immunology, 6th ed. ASM Press, Washington, DC.
6. Varga L, Széplaki G, Laki J, Kocsis A, Kristóf K, Gál P, Bajtay Z, Wieslander J, Daha MR, Garred P, Madsen HO, Füst G, Farkas H . 2008. Depressed activation of the lectin pathway of complement in hereditary angioedema. Clin Exp Immunol 153 : 68 74.[CrossRef].[PubMed]
7. Figueroa JE, Densen P . 1991. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 4 : 359 395.[PubMed].[CrossRef]
8. Giclas PC, . 2002. Choosing complement tests: differentiating between hereditary and acquired deficiency, p 111 116. In Rose NR, Hamilton RG, Detrick B (ed), Manual of Clinical Laboratory Immunology, 6th ed. ASM Press, Washington, DC.
9. Sellar GC, Cockburn D, Reid KB . 1992. Localization of the gene cluster encoding the A, B, and C chains of human C1q to 1p34.1-1p36.3. Immunogenetics 35 : 214 216.[PubMed]
10. Shen N, Tsao BP . 2004. Current advances in the human lupus genetics. Curr Rheumatol Rep 6 : 391 398.[PubMed].[CrossRef]
11. Tsao BP . 2000. Lupus susceptibility genes on human chromosome 1. Int Rev Immunol 19 : 319 334.[PubMed].[CrossRef]
12. Wisnieski JJ, Jones SM . 1992. Comparison of autoantibodies to the collagen-like region of C1q in hypocomplementemic urticarial vasculitis syndrome and systemic lupus erythematosus. J Immunol 148 : 1396 1403.[PubMed]
13. Kusumoto H, Hirosawa S, Salier JP, Hagen FS, Kurachi K . 1988. Human genes for complement components C1r and C1s in a close tail-to-tail arrangement. Proc Natl Acad Sci USA 85 : 7307 7311.[PubMed].[CrossRef]
14. Morgan BP, Walport MJ . 1991. Complement deficiency and disease. Immunol Today 12 : 301 306.[CrossRef].[PubMed]
15. Selander B, Mårtensson U, Weintraub A, Holmström E, Matsushita M, Thiel S, Jensenius JC, Truedsson L, Sjöholm AG . 2006. Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. J Clin Invest 116 : 1425 1434.[CrossRef].[PubMed]
16. Atkinson JP, Frank MM . 2006. Bypassing complement: evolutionary lessons and future implications. J Clin Invest 116 : 1215 1218.[CrossRef].[PubMed]
17. Mortensen JP, Buskjaer L, Lamm LU . 1980. Studies on the C2-deficiency gene in man. Immunology 39 : 541 549.[PubMed]
18. Atkinson JP, . 1999. Genetic susceptibility and class III complement genes, p 91 104. In Lahita RG (ed), Systemic Lupus Erythematosus. Academic Press, San Diego, CA.
19. Yu CY, Blanchong CA, Chung EK, Rupert KL, Yang Y, Yang Z, Zhou B, Moulds JM, . 2002. Molecular genetic analysis of human complement components C4A and C4B, p 117 131. In Rose NR, Hamilton RG, Detrick B (ed), Manual of Clinical Laboratory Immunology, 6th ed. ASM Press, Washington, DC.
20. Yang Y, Chung EK, Zhou B, Blanchong CA, Yu CY, Füst G, Kovács M, Vatay A, Szalai C, Karádi I, Varga L . 2003. Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index. J Immunol 171 : 2734 2745.[PubMed].[CrossRef]
21. Stefansson Thors V, Kolka R, Sigurdardottir SL, Edvardsson VO, Arason G, Haraldsson A . 2005. Increased frequency of C4B*Q0 alleles in patients with Henoch-Schönlein purpura. Scand J Immunol 61 : 274 278.[CrossRef].[PubMed]
22. Soto K, Wu YL, Ortiz A, Aparício SR, Yu CY . 2010. Familial C4B deficiency and immune complex glomerulonephritis. Clin Immunol 137 : 166 175.[CrossRef].[PubMed]
23. Atkinson JP . 1989. Complement deficiency: predisposing factor to autoimmune syndromes. Clin Exp Rheumatol 7( Suppl 3) : S95 S101.
24. Johnson CA, Densen P, Wetsel RA, Cole FS, Goeken NE, Colten HR . 1992. Molecular heterogeneity of C2 deficiency. N Engl J Med 326 : 871 874.[CrossRef].[PubMed]
25. Turner MW . 2003. The role of mannose-binding lectin in health and disease. Mol Immunol 40 : 423 429.[PubMed].[CrossRef]
26. Matsushita M, Endo Y, Fujita T . 2000. Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J Immunol 164 : 2281 2284.[PubMed].[CrossRef]
27. Casanova JL, Abel L . 2004. Human mannose-binding lectin in immunity: friend, foe, or both? J Exp Med 199 : 1295 1299.[CrossRef].[PubMed]
28. Bork K, Wulff K, Witske 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 : 129 134.[CrossRef].[PubMed]
29. Turner MW . 2003. The role of mannose-binding lectin in health and disease. Mol Immunol 40 : 423 429.[PubMed].[CrossRef]
30. Carlsson M, Sjöholm AG, Eriksson L, Thiel S, Jensenius JC, Segelmark M, Truedsson L . 2005. 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 139 : 306 313.[CrossRef].[PubMed]
31. Gadjeva M, Paludan SR, Thiel S, Slavov V, Ruseva M, Eriksson K, Löwhagen GB, Shi L, Takahashi K, Ezekowitz A, Jensenius JC . 2004. Mannan-binding lectin modulates the response to HSV-2 infection. Clin Exp Immunol 138 : 304 311.[CrossRef].[PubMed]
32. Hart ML, Ceonzo KA, Shaffer LA, Takahashi K, Rother RP, Reenstra WR, Buras JA, Stahl GL . 2005. Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q. J Immunol 174 : 6373 6380.[PubMed].[CrossRef]
33. Inanc N, Mumcu G, Birtas E, Elbir Y, Yavuz S, Ergun T, Fresko I, Direskeneli H . 2005. Serum mannose-binding lectin levels are decreased in behcet's disease and associated with disease severity. J Rheumatol 32 : 287 291.[PubMed]
34. Ip WK, Chan KH, Law HK, Tso GH, Kong EK, Wong WH, To YF, Yung RW, Chow EY, Au KL, Chan EY, Lim W, Jensenius JC, Turner MW, Peiris JS, Lau YL . 2005. Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection. J Infect Dis 191 : 1697 1704.[CrossRef].[PubMed]
35. Takahashi R, Tsutsumi A, Ohtani K, Goto D, Matsumoto I, Ito S, Wakamiya N, Sumida T . 2004. Anti-mannose binding lectin antibodies in sera of Japanese patients with systemic lupus erythematosus. Clin Exp Immunol 136 : 585 590.[CrossRef].[PubMed]
36. Foldager L, Köhler O, Steffensen R, Thiel S, Kristensen AS, Jensenius JC, Mors O . 2014. Bipolar and panic disorders may be associated with hereditary defects in the innate immune system. J Affect Disord 164 : 148 154.[CrossRef].[PubMed]
37. Lu J . 1997. Collectins: collectors of microorganisms for the innate immune system. BioEssays 19 : 509 518.[CrossRef].[PubMed]
38. Munthe-Fog L, Hummelshøj T, Honoré C, Madsen HO, Permin H, Garred P . 2009. Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency. N Engl J Med 360 : 2637 2644.[CrossRef].[PubMed]
39. Krarup A, Wallis R, Presanis JS, Gál P, Sim RB . 2007. Simultaneous activation of complement and coagulation by MBL-associated serine protease 2. PLoS One 2 : e623 10.1371/journal.pone.0000623.[CrossRef].[PubMed] http://dx.doi.org/10.1371/journal.pone.0000623
40. Gulla KC, Gupta K, Krarup A, Gal P, Schwaeble WJ, Sim RB, O'Connor CD, Hajela K . 2010. Activation of mannan-binding lectin-associated serine proteases leads to generation of a fibrin clot. Immunology 129 : 482 495.[CrossRef].[PubMed]
41. Schwaeble W, Dahl MR, Thiel S, Stover C, Jensenius JC . 2002. The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes. Immunobiology 205 : 455 466.[CrossRef].[PubMed]
42. Bork K . 2013. Hereditary angioedema with normal C1 inhibitor. Immunol Allergy Clin North Am 33 : 457 470.[CrossRef].[PubMed]
43. Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, Caballero T, Farkas H, Grumach A, Kaplan AP, Riedl MA, Triggiani M, Zanichelli A, Zuraw B HAWK under the patronage of EAACI (European Academy of Allergy and Clinical Immunology). 2014. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy 69 : 602 616.[CrossRef].[PubMed]
44. Frank MM . 2006. Hereditary angioedema: the clinical syndrome and its management in the United States. Immunol Allergy Clin North Am 26 : 653 668.[CrossRef].[PubMed]
45. Davis A, . 1998. C1 inhibitor gene and hereditary angioedema, p 229 283. In Volanakis JE, Frank MM (ed), The Human Complement System in Health and Disease. Marcel Dekker, New York, NY.
46. Frank MM, Gelfand JA, Atkinson JP . 1976. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med 84 : 580 593.[PubMed].[CrossRef]
47. Cicardi M, Agostoni A . 1996. Hereditary angioedema. N Engl J Med 334 : 1666 1667.[CrossRef].[PubMed]
48. Bowen B, Hawk JJ, Sibunka S, Hovick S, Weiler JM . 2001. A review of the reported defects in the human C1 esterase inhibitor gene producing hereditary angioedema including four new mutations. Clin Immunol 98 : 157 163.[CrossRef].[PubMed]
49. Binkley KE, Davis AE III . 2003. Estrogen-dependent inherited angioedema. Transfus Apheresis Sci 29 : 215 219.[CrossRef]
50. Kränke B, Salmhofer W, Aberer W . 2000. Hereditary angioedema and normal C1-inhibitor activity in women. Lancet 356 : 1440 1441.[CrossRef].[PubMed]
51. Melamed J, Alper CA, Cicardi M, Rosen FS . 1986. The metabolism of C1 inhibitor and C1q in patients with acquired C1-inhibitor deficiency. J Allergy Clin Immunol 77 : 322 326.[PubMed].[CrossRef]
52. Castelli R, Deliliers DL, Zingale LC, Pogliani EM, Cicardi M . 2007. Lymphoproliferative disease and acquired C1 inhibitor deficiency. Haematologica 92 : 716 718.[PubMed].[CrossRef]
53. Jackson J, Sim RB, Whaley K, Feighery C . 1989. Autoantibody facilitated cleavage of C1-inhibitor in autoimmune angioedema. J Clin Invest 83 : 698 707.[CrossRef].[PubMed]
54. Fujita T, Gigli I, Nussenzweig V . 1978. Human C4-binding protein. II. Role in proteolysis of C4b by C3b-inactivator. J Exp Med 148 : 1044 1051.[PubMed].[CrossRef]
55. Liu CC, Manzi S, Kao AH, Navratil JS, Ruffing MJ, Ahearn JM . 2005. Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus. Arthritis Rheum 52 : 3087 3099.[CrossRef].[PubMed]
56. Kao AH, Navratil JS, Ruffing MJ, Liu CC, Hawkins D, McKinnon KM, Danchenko N, Ahearn JM, Manzi S . 2010. Erythrocyte C3d and C4d for monitoring disease activity in systemic lupus erythematosus. Arthritis Rheum 62 : 837 844.[CrossRef].[PubMed]
57. Gronski P, Bodenbender L, Kanzy EJ, Seiler FR . 1988. C4-binding protein prevents spontaneous cleavage of C3 in sera of patients with hereditary angioedema. Complement 5 : 1 12.[PubMed]
58. Blom AM, Villoutreix BO, Dahlbäck B . 2004. Functions of human complement inhibitor C4b-binding protein in relation to its structure. Arch Immunol Ther Exp (Warsz) 52 : 83 95.[PubMed]
59. Trapp RG, Fletcher M, Forristal J, West CD . 1987. C4 binding protein deficiency in a patient with atypical Behçet's disease. J Rheumatol 14 : 135 138.[PubMed]
60. Volanakis JE, Narayana SV . 1996. Complement factor D, a novel serine protease. Protein Sci 5 : 553 564.[CrossRef].[PubMed]
61. White RT, Damm D, Hancock N, Rosen BS, Lowell BB, Usher P, Flier JS, Spiegelman BM . 1992. Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem 267 : 9210 9213.[PubMed]
62. Biesma DH, Hannema AJ, van Velzen-Blad H, Mulder L, van Zwieten R, Kluijt I, Roos D . 2001. A family with complement factor D deficiency. J Clin Invest 108 : 233 240.[CrossRef].[PubMed]
63. Kildsgaard J, Zsigmond E, Chan L, Wetsel RA . 1999. A critical evaluation of the putative role of C3adesArg (ASP) in lipid metabolism and hyperapobetalipoproteinemia. Mol Immunol 36 : 869 876.[PubMed].[CrossRef]
64. Cianflone K, Xia Z, Chen LY . 2003. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta 1609 : 127 143.[PubMed].[CrossRef]
65. Carroll MC, Campbell RD, Bentley DR, Porter RR . 1984. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature 307 : 237 241.[PubMed].[CrossRef]
66. Mortensen JP, Lamm LU . 1981. Quantitative differences between complement factor-B phenotypes. Immunology 42 : 505 511.[PubMed]
67. Slade C, Bosco J, Unglik G, Bleasel K, Nagel M, Winship I . 2013. Deficiency in complement factor B. N Engl J Med 369 : 1667 1669.[CrossRef].[PubMed]
68. Farries TC, Lachmann PJ, Harrison RA . 1988. Analysis of the interaction between properdin and factor B, components of the alternative-pathway C3 convertase of complement. Biochem J 253 : 667 675.[PubMed].[CrossRef]
69. Farries TC, Lachmann PJ, Harrison RA . 1988. Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products. Biochem J 252 : 47 54.[PubMed].[CrossRef]
70. Cortes C, Ohtola JA, Saggu G, Ferreira VP . 2012. Local release of properdin in the cellular microenvironment: role in pattern recognition and amplification of the alternative pathway of complement. Front Immunol 3 : 412. doi:10.3389/fimmu.2012.00412.[CrossRef].[PubMed] http://dx.doi.org/doi:10.3389/fimmu.2012.00412
71. Hourcade DE . 2006. The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem 281 : 2128 2132.[CrossRef].[PubMed]
72. Sjöholm AG, Braconier JH, Söderström C . 1982. Properdin deficiency in a family with fulminant meningococcal infections. Clin Exp Immunol 50 : 291 297.[PubMed]
73. Goundis D, Holt SM, Boyd Y, Reid KB . 1989. Localization of the properdin structural locus to Xp11.23-Xp21.1. Genomics 5 : 56 60.[PubMed].[CrossRef]
74. Frémeaux-Bacchi V, Le Coustumier A, Blouin J, Kazatchkine MD, Weiss L . 1995. [Partial properdin deficiency revealed by a septicemia caused by Neisseria meningitidis.]. Presse Med 24 : 1305 1307. (In French.)[PubMed]
75. Westberg J, Fredrikson GN, Truedsson L, Sjöholm AG, Uhlén M . 1995. Sequence-based analysis of properdin deficiency: identification of point mutations in two phenotypic forms of an X-linked immunodeficiency. Genomics 29 : 1 8.[CrossRef].[PubMed]
76. Kölble K, Cant AJ, Fay AC, Whaley K, Schlesinger M, Reid KB . 1993. Carrier detection in families with properdin deficiency by microsatellite haplotyping. J Clin Invest 91 : 99 102.[CrossRef].[PubMed]
77. Fearon DT . 1979. Activation of the alternative complement pathway. CRC Crit Rev Immunol 1 : 1 32.[PubMed]
78. Harrison RA, Farries TC, Northrop FD, Lachmann PJ, Davis AE . 1988. Structure of C3f, a small peptide specifically released during inactivation of the third component of complement. Complement 5 : 27 32.[PubMed]
79. Liszewski MK, Post TW, Atkinson JP . 1991. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol 9 : 431 455.[CrossRef].[PubMed]
80. Hing S, Day AJ, Linton SJ, Ripoche J, Sim RB, Reid KB, Solomon E . 1988. Assignment of complement components C4 binding protein (C4BP) and factor H (FH) to human chromosome 1q, using cDNA probes. Ann Hum Genet 52 : 117 122.[PubMed].[CrossRef]
81. Estaller C, Schwaeble W, Dierich M, Weiss EH . 1991. Human complement factor H: two factor H proteins are derived from alternatively spliced transcripts. Eur J Immunol 21 : 799 802.[CrossRef].[PubMed]
82. Nabil K, Rihn B, Jaurand MC, Vignaud JM, Ripoche J, Martinet Y, Martinet N . 1997. Identification of human complement factor H as a chemotactic protein for monocytes. Biochem J 326 : 377 383.[PubMed].[CrossRef]
83. Ohtsuka H, Imamura T, Matsushita M, Tanase S, Okada H, Ogawa M, Kambara T . 1993. Thrombin generates monocyte chemotactic activity from complement factor H. Immunology 80 : 140 145.[PubMed]
84. Ault BH . 2000. Factor H and the pathogenesis of renal diseases. Pediatr Nephrol 14 : 1045 1053.[PubMed].[CrossRef]
85. Moseley HL, Whaley K . 1980. Control of complement activation in membranous and membranoproliferative glomerulonephritis. Kidney Int 17 : 535 544.[PubMed].[CrossRef]
86. Nielsen HE, Christensen KC, Koch C, Thomsen BS, Heegaard NH, Tranum-Jensen J . 1989. Hereditary, complete deficiency of complement factor H associated with recurrent meningococcal disease. Scand J Immunol 30 : 711 718.[PubMed].[CrossRef]
87. Edwards AO, Ritter R III, Abel KJ, Manning A, Panhuysen C, Farrer LA . 2005. Complement factor H polymorphism and age-related macular degeneration. Science 308 : 421 424.[CrossRef].[PubMed]
88. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R . 2005. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 102 : 7227 7232.[CrossRef].[PubMed]
89. Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA . 2005. Complement factor H variant increases the risk of age-related macular degeneration. Science 308 : 419 421.[CrossRef].[PubMed]
90. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J . 2005. Complement factor H polymorphism in age-related macular degeneration. Science 308 : 385 389.[CrossRef].[PubMed]
91. Richards A, Goodship JA, Goodship TH . 2002. The genetics and pathogenesis of haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Curr Opin Nephrol Hypertens 11 : 431 435.[PubMed].[CrossRef]
92. Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, Müslümanoğlu MH, Kavukcu S, Filler G, Pirson Y, Wen LS, Atkinson JP, Goodship TH . 2003. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci USA 100 : 12966 12971.[CrossRef].[PubMed]
93. Dragon-Durey MA, Blanc C, Garnier A, Hofer J, Sethi SK, Zimmerhackl LB . 2010. Anti-factor H autoantibody-associated hemolytic uremic syndrome: review of literature of the autoimmune form of HUS. Semin Thromb Hemost 36 : 633 640.[CrossRef].[PubMed]
94. Skerka C, Józsi M, Zipfel PF, Dragon-Durey MA, Fremeaux-Bacchi V . 2009. Autoantibodies in haemolytic uraemic syndrome (HUS). Thromb Haemost 101 : 227 232.[PubMed]
95. Roumenina LT, Roquigny R, Blanc C, Poulain N, Ngo S, Dragon-Durey MA, Frémeaux-Bacchi V . 2014. Functional evaluation of factor H genetic and acquired abnormalities: application for atypical hemolytic uremic syndrome (aHUS). Methods Mol Biol 1100 : 237 247.[CrossRef].[PubMed]
96. China B, Sory MP, N'Guyen BT, De Bruyere M, Cornelis GR . 1993. Role of the YadA protein in prevention of opsonization of Yersinia enterocolitica by C3b molecules. Infect Immun 61 : 3129 3136.[PubMed]
97. Horstmann RD, Sievertsen HJ, Knobloch J, Fischetti VA . 1988. Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci USA 85 : 1657 1661.[PubMed].[CrossRef]
98. McDowell JV, Wolfgang J, Tran E, Metts MS, Hamilton D, Marconi RT . 2003. Comprehensive analysis of the factor h binding capabilities of borrelia species associated with lyme disease: delineation of two distinct classes of factor h binding proteins. Infect Immun 71 : 3597 3602.[PubMed].[CrossRef]
99. Roversi P, Johnson S, Caesar JJ, McLean F, Leath KJ, Tsiftsoglou SA, Morgan BP, Harris CL, Sim RB, Lea SM . 2011. Structural basis for complement factor I control and its disease-associated sequence polymorphisms. Proc Natl Acad Sci USA 108 : 12839 12844.[CrossRef].[PubMed]
100. Abramson N, Alper CA, Lachmann PJ, Rosen FS, Jandl JH . 1971. Deficiency of C3 inactivator in man. J Immunol 107 : 19 27.[PubMed]
101. Alper CA, Abramson N, Johnston RB Jr, Jandl JH, Rosen FS . 1970. Studies in vivo and in vitro on an abnormality in the metabolism of C3 in a patient with increased susceptibility to infection. J Clin Invest 49 : 1975 1985.[CrossRef].[PubMed]
102. Genel F, Sjöholm AG, Skattum L, Truedsson L . 2005. Complement factor I deficiency associated with recurrent infections, vasculitis and immune complex glomerulonephritis. Scand J Infect Dis 37 : 615 618.[PubMed].[CrossRef]
103. Vyse TJ, Morley BJ, Bartok I, Theodoridis EL, Davies KA, Webster AD, Walport MJ . 1996. The molecular basis of hereditary complement factor I deficiency. J Clin Invest 97 : 925 933.[CrossRef].[PubMed]
104. Whitehead AS, Solomon E, Chambers S, Bodmer WF, Povey S, Fey G . 1982. Assignment of the structural gene for the third component of human complement to chromosome 19. Proc Natl Acad Sci USA 79 : 5021 5025.[PubMed].[CrossRef]
105. Schoonbrood TH, Hannema A, Fijen CA, Markusse HM, Swaak AJ . 1995. C5 deficiency in a patient with primary Sjögren's syndrome. J Rheumatol 22 : 1389 1390.[PubMed]
106. Ramos-Casals M, Brito-Zerón P, Yagüe J, Akasbi M, Bautista R, Ruano M, Claver G, Gil V, Font J . 2005. Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome. Rheumatology (Oxford) 44 : 89 94.[CrossRef].[PubMed]
107. Asghar SS, Venneker GT, van Meegen M, Meinardi MM, Hulsmans RF, de Waal LP . 1991. Hereditary deficiency of C5 in association with discoid lupus erythematosus. J Am Acad Dermatol 24 : 376 378.[PubMed].[CrossRef]
108. Salvadori M, Bertoni E . 2013. Update on hemolytic uremic syndrome: diagnostic and therapeutic recommendations. World J Nephrol 2 : 56 76.[CrossRef].[PubMed]
109. Fernie BA, Würzner R, Orren A, Morgan BP, Potter PC, Platonov AE, Vershinina IV, Shipulin GA, Lachmann PJ, Hobart MJ . 1996. Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in combination with other C6 and C7 deficiencies. J Immunol 157 : 3648 3657.[PubMed]
110. Tedesco F, Densen P, Villa MA, Petersen BH, Sirchia G . 1983. Two types of dysfunctional eighth component of complement (C8) molecules in C8 deficiency in man. Reconstitution of normal C8 from the mixture of two abnormal C8 molecules. J Clin Invest 71 : 183 191.[PubMed].[CrossRef]
111. Kaufman KM, Sodetz JM . 1994. Genomic structure of the human complement protein C8 gamma: homology to the lipocalin gene family. Biochemistry 33 : 5162 5166.[PubMed].[CrossRef]
112. Müller-Eberhard HJ . 1985. The killer molecule of complement. J Invest Dermatol 85( Suppl) : 47s 52s.[PubMed].[CrossRef]
113. Fukumori Y, Yoshimura K, Ohnoki S, Yamaguchi H, Akagaki Y, Inai S . 1989. A high incidence of C9 deficiency among healthy blood donors in Osaka, Japan. Int Immunol 1 : 85 89.[PubMed].[CrossRef]
114. Kang HJ, Kim HS, Lee YK, Cho HC . 2005. High incidence of complement C9 deficiency in Koreans. Ann Clin Lab Sci 35 : 144 148.[PubMed]
115. Hobart MJ, Fernie BA, Würzner R, Oldroyd RG, Harrison RA, Joysey V, Lachmann PJ . 1997. Difficulties in the ascertainment of C9 deficiency: lessons to be drawn from a compound heterozygote C9-deficient subject. Clin Exp Immunol 108 : 500 506.[PubMed].[CrossRef]
116. Barrett DJ, Boyle MD . 1984. Restoration of complement function in vivo by plasma infusion in factor I (C3b inactivator) deficiency. J Pediatr 104 : 76 81.[PubMed].[CrossRef]
117. Perry G, Eisenberg PR, Zimmerman JL, Levin J . 1998. Phase I safety trial of soluble complement receptor type (TP 10) on acute myocardial infarction. J Am Coll Cardiol 31( 2s2) : 411A.
118. Quigg RJ, Kozono Y, Berthiaume D, Lim A, Salant DJ, Weinfeld A, Griffin P, Kremmer E, Holers VM . 1998. Blockade of antibody-induced glomerulonephritis with Crry-Ig, a soluble murine complement inhibitor. J Immunol 160 : 4553 4560.[PubMed]
119. Ricklin D, Lambris JD . 2013. Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol 190 : 3839 3847.[CrossRef].[PubMed]
120. Lachmann PJ, Smith RA . 2009. Taking complement to the clinic—has the time finally come? Scand J Immunol 69 : 471 478.[CrossRef].[PubMed]
121. Hertle E, Stehouer CDA, van Greevenbroek MMJ . 2014. The complement system in human cardiometabolic disease. Mol Immunol 61 : 135 148.[CrossRef].[PubMed]


Generic image for table

Testing for complement deficiency or dysfunction

Citation: Giclas P. 2016. Hereditary and Acquired Complement Deficiencies, p 749-765. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch77

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error