Complement system part II: Role in immunity

Frontiers in Immunology

Volumn 6, Issue MAY, 2015, Pages

  Merle, Nicolas S ^a,b   Noe, Remi ^a,b,c   Halbwachs Mecarelli, Lise ^a,b   Fremeaux Bacchi, Veronique ^a,b,d   Roumenina, Lubka T ^a,b  

^a CENTRE DE RECHERCHE DES CORDELIERS   (France)

^b SORBONNE UNIVERSITÉ   (France)

^c PSL RESEARCH UNIVERSITY   (France)

^d HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

Author keywords

Adaptive immunity; Anaphylatoxins; Complement and innate immunity; Complement in cancer; Complement system; Complement related diseases; Crosstalk TLR complement; Pathogen strategies for immune evasion

Indexed keywords

ANAPHYLATOXIN; CD18 ANTIGEN; COMPLEMENT COMPONENT C3A; COMPLEMENT COMPONENT C5A; CYTOKINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 27; INTERLEUKIN 37; INTERLEUKIN 6; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PENTRAXIN 3; PHOSPHATIDYLINOSITOL 3 KINASE; PROSTAGLANDIN E2; PROTEIN KINASE B; STRESS ACTIVATED PROTEIN KINASE; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR 4; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; AGE RELATED MACULAR DEGENERATION; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; APOPTOSIS; CELL SURVIVAL; COMPLEMENT ACTIVATION; COMPLEMENT SYSTEM; DISEASE ASSOCIATION; GLOMERULOPATHY; HEMOLYTIC UREMIC SYNDROME; HOMEOSTASIS; HUMAN; IMMUNOSURVEILLANCE; INFLAMMATION; INNATE IMMUNITY; NEOPLASM; NONHUMAN; OPSONIZATION; PHAGOCYTOSIS; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS;

EID: 84935041763     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00257     Document Type: Review

References (282)

1. Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I-molecular mechanisms of activation and regulation. Front Immunol (2015) 6:262. doi:10.3389/fimmu.2015.00262
2. Lachmann PJ, Halbwachs L. The influence of C3b inactivator (KAF) concentration on the ability of serum to support complement activation. Clin Exp Immunol (1975) 21:109-14.
3. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ (2009) 16:3-11. doi:10.1038/cdd.2008.150
4. Galvan MD, Greenlee-Wacker MC, Bohlson SS. C1q and phagocytosis: the perfect complement to a good meal. J Leukoc Biol (2012) 92:489-97. doi:10.1189/jlb.0212099
5. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol (2010) 11:785-97. doi:10.1038/ni.1923
6. Païdassi H, Tacnet-Delorme P, Garlatti V, Darnault C, Ghebrehiwet B, Gaboriaud C, et al. C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition. J Immunol (2008) 1950(180):2329-38. doi:10.4049/jimmunol.180.4.2329
7. Païdassi H, Tacnet-Delorme P, Verneret M, Gaboriaud C, Houen G, Duus K, et al. Investigations on the C1q-calreticulin-phosphatidylserine interactions yield new insights into apoptotic cell recognition. J Mol Biol (2011) 408:277-90. doi:10.1016/j.jmb.2011.02.029
8. Terrasse R, Tacnet-Delorme P, Moriscot C, Pérard J, Schoehn G, Vernet T, et al. Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein. J Biol Chem (2012) 287:42620-33. doi:10.1074/jbc. M112.423731
9. Verneret M, Tacnet-Delorme P, Osman R, Awad R, Grichine A, Kleman J-P, et al. Relative contribution of c1q and apoptotic cell-surface calreticulin to macrophage phagocytosis. J Innate Immun (2014) 6:426-34. doi:10.1159/000358834
10. Fraser DA, Laust AK, Nelson EL, Tenner AJ. C1q differentially modulates phagocytosis and cytokine responses during ingestion of apoptotic cells by human monocytes, macrophages, and dendritic cells. J Immunol (2009) 1950(183):6175-85. doi:10.4049/jimmunol.0902232
11. Castellano G, Woltman AM, Schlagwein N, Xu W, Schena FP, Daha MR, et al. Immune modulation of human dendritic cells by complement. Eur J Immunol (2007) 37:2803-11. doi:10.1002/eji.200636845
12. Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol (2000) 76:227-324. doi:10.1016/S0065-2776(01)76021-X
13. Roumenina LT, Sène D, Radanova M, Blouin J, Halbwachs-Mecarelli L, Dragon-Durey M-A, et al. Functional complement C1q abnormality leads to impaired immune complexes and apoptotic cell clearance. J Immunol (2011) 1950(187):4369-73. doi:10.4049/jimmunol.1101749
14. Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, Fadok VA, et al. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med (2001) 194:781-95. doi:10.1084/jem.194.6.781
15. Benoit ME, Clarke EV, Morgado P, Fraser DA, Tenner AJ. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells. J Immunol (2012) 1950(188):5682-93. doi:10.4049/jimmunol.1103760
16. Clarke EV, Weist BM, Walsh CM, Tenner AJ. Complement protein C1q bound to apoptotic cells suppresses human macrophage and dendritic cell-mediated Th17 and Th1 T cell subset proliferation. J Leukoc Biol (2015) 97:147-60. doi:10.1189/jlb.3A0614-278R
17. Walport MJ. Complement. Second of two parts. N Engl J Med (2001) 344:1140-4. doi:10.1056/NEJM200104123441506
18. Baruah P, Dumitriu IE, Malik TH, Cook HT, Dyson J, Scott D, et al. C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells. Blood (2009) 113:3485-93. doi:10.1182/blood-2008-06-164392
19. Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T, et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J (2012) 31:1062-79. doi:10.1038/emboj.2011.497
20. Said G, Guilbert M, Morjani H, Garnotel R, Jeannesson P, El Btaouri H. Extracellular matrix proteins modulate antimigratory and apoptotic effects of doxorubicin. Chemother Res Pract (2012) 2012:268681. doi:10.1155/2012/268681
21. Amarilyo G, Verbovetski I, Atallah M, Grau A, Wiser G, Gil O, et al. iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-kappaB-dependent blockade. Eur J Immunol (2010) 40:699-709. doi:10.1002/eji.200838951
22. Mevorach D, Mascarenhas JO, Gershov D, Elkon KB. Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med (1998) 188:2313-20. doi:10.1084/jem.188.12.2313
23. Morelli AE, Larregina AT, Shufesky WJ, Zahorchak AF, Logar AJ, Papworth GD, et al. Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production. Blood (2003) 101:611-20. doi:10.1182/blood-2002-06-1769
24. Verbovetski I, Bychkov H, Trahtemberg U, Shapira I, Hareuveni M, Ben-Tal O, et al. Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7. J Exp Med (2002) 196:1553-61. doi:10.1084/jem.20020263
25. Liszewski MK, Kolev M, Le Friec G, Leung M, Bertram PG, Fara AF, et al. Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity (2013) 39:1143-57. doi:10.1016/j.immuni.2013.10.018
26. André C, Cota D. Coupling nutrient sensing to metabolic homoeostasis: the role of the mammalian target of rapamycin complex 1 pathway. Proc Nutr Soc (2012) 71:502-10. doi:10.1017/S0029665112000754
27. Strainic MG, Liu J, Huang D, An F, Lalli PN, Muqim N, et al. Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity (2008) 28:425-35. doi:10.1016/j.immuni.2008.02.001
28. Peng Q, Li K, Patel H, Sacks SH, Zhou W. Dendritic cell synthesis of C3 is required for full T cell activation and development of a Th1 phenotype. J Immunol (2006) 1950(176):3330-41. doi:10.4049/jimmunol.176.6.3330
29. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci (2009) 122:3589-94. doi:10.1242/jcs.051011
30. Kishore U, Ghai R, Greenhough TJ, Shrive AK, Bonifati DM, Gadjeva MG, et al. Structural and functional anatomy of the globular domain of complement protein C1q. Immunol Lett (2004) 95:113-28. doi:10.1016/j.imlet.2004.06.015
31. Roumenina LT, Popov KT, Bureeva SV, Kojouharova M, Gadjeva M, Rabheru S, et al. Interaction of the globular domain of human C1q with Salmonella typhimurium lipopolysaccharide. Biochim Biophys Acta (2008) 1784:1271-6. doi:10.1016/j.bbapap.2008.04.029
32. Albertí S, Marqués G, Hernández-Allés S, Rubires X, Tomás JM, Vivanco F, et al. Interaction between complement subcomponent C1q and the Klebsiella pneumoniae porin OmpK36. Infect Immun (1996) 64:4719-25.
33. Ezekowitz RA. Role of the mannose-binding lectin in innate immunity. J Infect Dis (2003) 187(Suppl 2):S335-9. doi:10.1086/374746
34. Dimitrov JD, Planchais C, Roumenina LT, Vassilev TL, Kaveri SV, Lacroix-Desmazes S. Antibody polyreactivity in health and disease: statu variabilis. J Immunol (2013) 1950(191):993-9. doi:10.4049/jimmunol.1300880
35. Gaboriaud C, Thielens NM, Gregory LA, Rossi V, Fontecilla-Camps JC, Arlaud GJ. Structure and activation of the C1 complex of complement: unraveling the puzzle. Trends Immunol (2004) 25:368-73. doi:10.1016/j.it.2004.04.008
36. Roumenina LT, Kantardjiev AA, Atanasov BP, Waters P, Gadjeva M, Reid KBM, et al. Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. Biochemistry (2005) 44:14097-109. doi:10.1021/bi051186n
37. Kjaer TR, Thiel S, Andersen GR. Toward a structure-based comprehension of the lectin pathway of complement. Mol Immunol (2013) 56:413-22. doi:10.1016/j.molimm.2013.05.220
38. Degn SE, Kjaer TR, Kidmose RT, Jensen L, Hansen AG, Tekin M, et al. Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes. Proc Natl Acad Sci U S A (2014) 111:13445-50. doi:10.1073/pnas.1406849111
39. Kidmose RT, Laursen NS, Dobó J, Kjaer TR, Sirotkina S, Yatime L, et al. Structural basis for activation of the complement system by component C4 cleavage. Proc Natl Acad Sci U S A (2012) 109:15425-30. doi:10.1073/pnas.1208031109
40. Gál P, Harmat V, Kocsis A, Bián T, Barna L, Ambrus G, et al. A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations. J Biol Chem (2005) 280:33435-44. doi:10.1074/jbc. M506051200
41. Kinoshita T, Takata Y, Kozono H, Takeda J, Hong KS, Inoue K. C5 convertase of the alternative complement pathway: covalent linkage between two C3b molecules within the trimolecular complex enzyme. J Immunol (1988) 1950(141):3895-901.
42. Bubeck D. The making of a macromolecular machine: assembly of the membrane attack complex. Biochemistry (2014) 53:1908-15. doi:10.1021/bi500157z
43. Joiner K, Brown E, Hammer C, Warren K, Frank M. Studies on the mechanism of bacterial resistance to complement-mediated killing. III. C5b-9 deposits stably on rough and type 7 S. pneumoniae without causing bacterial killing. J Immunol (1983) 130:845-9.
44. Bhakdi S, Kuller G, Muhly M, Fromm S, Seibert G, Parrisius J. Formation of transmural complement pores in serum-sensitive Escherichia coli. Infect Immun (1987) 55:206-10.
45. Lewis LA, Ram S. Meningococcal disease and the complement system. Virulence (2014) 5:98-126. doi:10.4161/viru.26515
46. Cole DS, Morgan BP. Beyond lysis: how complement influences cell fate. Clin Sci (Lond) (2003) 1979(104):455-66. doi:10.1042/CS20020362
47. Morgan BP. Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects. Biochem J (1989) 264:1-14.
48. Campbell DG, Gagnon J, Reid KB, Williams AF. Rat brain Thy-1 glycoprotein. The amino acid sequence, disulphide bonds and an unusual hydrophobic region. Biochem J (1981) 195:15-30.
49. Morgan BP, Campbell AK. The recovery of human polymorphonuclear leucocytes from sublytic complement attack is mediated by changes in intracellular free calcium. Biochem J (1985) 231:205-8.
50. Bohnsack JF, O'Shea JJ, Takahashi T, Brown EJ. Fibronectin-enhanced phagocytosis of an alternative pathway activator by human culture-derived macrophages is mediated by the C4b/C3b complement receptor (CR1). J Immunol (1985) 1950(135):2680-6.
51. Griffin FM, Mullinax PJ. High concentrations of bacterial lipopolysaccharide, but not microbial infection-induced inflammation, activate macrophage C3 receptors for phagocytosis. J Immunol (1990) 1950(145):697-701.
52. Tosi MF, Zakem H, Berger M. Neutrophil elastase cleaves C3bi on opsonized Pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. J Clin Invest (1990) 86:300-8. doi:10.1172/JCI114699
53. Dupuy AG, Caron E. Integrin-dependent phagocytosis: spreading from microadhesion to new concepts. J Cell Sci (2008) 121:1773-83. doi:10.1242/jcs.018036
54. Uotila LM, Aatonen M, Gahmberg CG. Integrin CD11c/CD18 α-chain phosphorylation is functionally important. J Biol Chem (2013) 288:33494-9. doi:10.1074/jbc. C113.497446
55. Ross GD, Vetvicka V. CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions. Clin Exp Immunol (1993) 92:181-4. doi:10.1111/j.1365-2249.1993.tb03377.x
56. Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol (1999) 17:593-623. doi:10.1146/annurev.immunol.17.1.593
57. Gorgani NN, He JQ, Katschke KJ, Helmy KY, Xi H, Steffek M, et al. Complement receptor of the Ig superfamily enhances complement-mediated phagocytosis in a subpopulation of tissue resident macrophages. J Immunol (2008) 1950(181):7902-8. doi:10.4049/jimmunol.181.11.7902
58. Mayadas TN, Cullere X. Neutrophil beta2 integrins: moderators of life or death decisions. Trends Immunol (2005) 26:388-95. doi:10.1016/j.it.2005.05.002
59. Klos A, Tenner AJ, Johswich K-O, Ager RR, Reis ES, Köhl J. The role of the anaphylatoxins in health and disease. Mol Immunol (2009) 46:2753-66. doi:10.1016/j.molimm.2009.04.027
60. Klos A, Wende E, Wareham KJ, Monk PN. International union of basic and clinical pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev (2013) 65:500-43. doi:10.1124/pr.111.005223
61. Murakami Y, Imamichi T, Nagasawa S. Characterization of C3a anaphylatoxin receptor on guinea-pig macrophages. Immunology (1993) 79:633-8.
62. Elsner J, Oppermann M, Czech W, Dobos G, Schöpf E, Norgauer J, et al. C3a activates reactive oxygen radical species production and intracellular calcium transients in human eosinophils. Eur J Immunol (1994) 24:518-22. doi:10.1002/eji.1830240304
63. Elsner J, Oppermann M, Czech W, Kapp A. C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins. Blood (1994) 83:3324-31.
64. Kretzschmar T, Jeromin A, Gietz C, Bautsch W, Klos A, Köhl J, et al. Chronic myelogenous leukemia-derived basophilic granulocytes express a functional active receptor for the anaphylatoxin C3a. Eur J Immunol (1993) 23:558-61. doi:10.1002/eji.1830230239
65. el-Lati SG, Dahinden CA, Church MK. Complement peptides C3a-and C5a-induced mediator release from dissociated human skin mast cells. J Invest Dermatol (1994) 102:803-6. doi:10.1111/1523-1747.ep12378589
66. Coulthard LG, Woodruff TM. Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. J Immunol (2015) 1950(194):3542-8. doi:10.4049/jimmunol.1403068
67. Chen N-J, Mirtsos C, Suh D, Lu Y-C, Lin W-J, McKerlie C, et al. C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a. Nature (2007) 446:203-7. doi:10.1038/nature05559
68. Daffern PJ, Pfeifer PH, Ember JA, Hugli TE. C3a is a chemotaxin for human eosinophils but not for neutrophils. I. C3a stimulation of neutrophils is secondary to eosinophil activation. J Exp Med (1995) 181:2119-27. doi:10.1084/jem.181.6.2119
69. Hollmann TJ, Mueller-Ortiz SL, Braun MC, Wetsel RA. Disruption of the C5a receptor gene increases resistance to acute Gram-negative bacteremia and endotoxic shock: opposing roles of C3a and C5a. Mol Immunol (2008) 45:1907-15. doi:10.1016/j.molimm.2007.10.037
70. Wu MCL, Brennan FH, Lynch JPL, Mantovani S, Phipps S, Wetsel RA, et al. The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization. Proc Natl Acad Sci U S A (2013) 110:9439-44. doi:10.1073/pnas.1218815110
71. Tsuruta T, Yamamoto T, Matsubara S, Nagasawa S, Tanase S, Tanaka J, et al. Novel function of C4a anaphylatoxin. Release from monocytes of protein which inhibits monocyte chemotaxis. Am J Pathol (1993) 142:1848-57.
72. Zhao Y, Xu H, Yu W, Xie B-D. Complement anaphylatoxin C4a inhibits C5a-induced neointima formation following arterial injury. Mol Med Rep (2014) 10:45-52. doi:10.3892/mmr.2014.2176
73. Barnum SR. C4a: an anaphylatoxin in name only. J Innate Immun (2015). doi:10.1159/000371423
74. Campbell WD, Lazoura E, Okada N, Okada H. Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N. Microbiol Immunol (2002) 46:131-4. doi:10.1111/j.1348-0421.2002.tb02669.x
75. Matthews KW, Mueller-Ortiz SL, Wetsel RA. Carboxypeptidase N: a pleiotropic regulator of inflammation. Mol Immunol (2004) 40:785-93. doi:10.1016/j.molimm.2003.10.002
76. Mueller-Ortiz SL, Wang D, Morales JE, Li L, Chang J-Y, Wetsel RA. Targeted disruption of the gene encoding the murine small subunit of carboxypeptidase N (CPN1) causes susceptibility to C5a anaphylatoxin-mediated shock. J Immunol (2009) 1950(182):6533-9. doi:10.4049/jimmunol.0804207
77. Shao Z, Nishimura T, Leung LLK, Morser J. Carboxypeptidase B2 deficiency reveals opposite effects of complement C3a and C5a in a murine polymicrobial sepsis model. J Thromb Haemost (2015). doi:10.1111/jth.12956
78. Sayah S, Jauneau AC, Patte C, Tonon MC, Vaudry H, Fontaine M. Two different transduction pathways are activated by C3a and C5a anaphylatoxins on astrocytes. Brain Res Mol Brain Res (2003) 112:53-60. doi:10.1016/S0169-328X(03)00046-9
79. Schatz-Jakobsen JA, Yatime L, Larsen C, Petersen SV, Klos A, Andersen GR. Structural and functional characterization of human and murine C5a anaphylatoxins. Acta Crystallogr D Biol Crystallogr (2014) 70:1704-17. doi:10.1107/S139900471400844X
80. Crass T, Raffetseder U, Martin U, Grove M, Klos A, Köhl J, et al. Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from differentiated U-937 cells. Eur J Immunol (1996) 26:1944-50. doi:10.1002/eji.1830260840
81. Wilken HC, Götze O, Werfel T, Zwirner J. C3a(desArg) does not bind to and signal through the human C3a receptor. Immunol Lett (1999) 67:141-5. doi:10.1016/S0165-2478(99)00002-4
82. Venkatesha RT, Berla Thangam E, Zaidi AK, Ali H. Distinct regulation of C3a-induced MCP-1/CCL2 and RANTES/CCL5 production in human mast cells by extracellular signal regulated kinase and PI3 kinase. Mol Immunol (2005) 42:581-7. doi:10.1016/j.molimm.2004.09.009
83. Hartmann K, Henz BM, Krüger-Krasagakes S, Köhl J, Burger R, Guhl S, et al. C3a and C5a stimulate chemotaxis of human mast cells. Blood (1997) 89:2863-70.
84. Asgari E, Le Friec G, Yamamoto H, Perucha E, Sacks SS, Köhl J, et al. C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation. Blood (2013) 122:3473-81. doi:10.1182/blood-2013-05-502229
85. Takabayashi T, Vannier E, Clark BD, Margolis NH, Dinarello CA, Burke JF, et al. A new biologic role for C3a and C3a desArg: regulation of TNF-alpha and IL-1 beta synthesis. J Immunol (1996) 1950(156):3455-60.
86. Fischer WH, Hugli TE. Regulation of B cell functions by C3a and C3a(desArg): suppression of TNF-alpha, IL-6, and the polyclonal immune response. J Immunol (1997) 1950(159):4279-86.
87. Peng Q, Li K, Anderson K, Farrar CA, Lu B, Smith RAG, et al. Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction. Blood (2008) 111:2452-61. doi:10.1182/blood-2007-06-095018
88. 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) 58:98-107. doi:10.1016/j.molimm.2013.11.010
89. Heeger PS, Kemper C. Novel roles of complement in T effector cell regulation. Immunobiology (2012) 217:216-24. doi:10.1016/j.imbio.2011.06.004
90. Goligorsky MS, Patschan D, Kuo M-C. Weibel-Palade bodies-sentinels of acute stress. Nat Rev Nephrol (2009) 5:423-6. doi:10.1038/nrneph.2009.87
91. Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem (1998) 67:395-424. doi:10.1146/annurev.biochem.67.1.395
92. del Conde I. Platelet activation leads to activation and propagation of the complement system. J Exp Med (2005) 201:871-9. doi:10.1084/jem.20041497
93. Morigi M, Galbusera M, Gastoldi S, Locatelli M, Buelli S, Pezzotta A, et al. Alternative pathway activation of complement by shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol (2011) 187:172-80. doi:10.4049/jimmunol.1100491
94. Gerard NP, Gerard C. The chemotactic receptor for human C5a anaphylatoxin. Nature (1991) 349:614-7. doi:10.1038/349614a0
95. Perianayagam MC, Balakrishnan VS, King AJ, Pereira BJG, Jaber BL. C5a delays apoptosis of human neutrophils by a phosphatidylinositol 3-kinase-signaling pathway. Kidney Int (2002) 61:456-63. doi:10.1046/j.1523-1755.2002.00139.x
96. la Sala A, Gadina M, Kelsall BL. G(i)-protein-dependent inhibition of IL-12 production is mediated by activation of the phosphatidylinositol 3-kinase-protein 3 kinase B/Akt pathway and JNK. J Immunol (2005) 1950(175):2994-9. doi:10.4049/jimmunol.175.5.2994
97. Jiang H, Kuang Y, Wu Y, Xie W, Simon MI, Wu D. Roles of phospholipase C beta2 in chemoattractant-elicited responses. Proc Natl Acad Sci U S A (1997) 94:7971-5. doi:10.1073/pnas.94.15.7971
98. Mullmann TJ, Siegel MI, Egan RW, Billah MM. Complement C5a activation of phospholipase D in human neutrophils. A major route to the production of phosphatidates and diglycerides. J Immunol (1990) 1950(144):1901-8.
99. Buhl AM, Avdi N, Worthen GS, Johnson GL. Mapping of the C5a receptor signal transduction network in human neutrophils. Proc Natl Acad Sci U S A (1994) 91:9190-4. doi:10.1073/pnas.91.19.9190
100. Aksamit RR, Falk W, Leonard EJ. Chemotaxis by mouse macrophage cell lines. J Immunol (1981) 1950(126):2194-9.
101. Ehrengruber MU, Geiser T, Deranleau DA. Activation of human neutrophils by C3a and C5A. Comparison of the effects on shape changes, chemotaxis, secretion, and respiratory burst. FEBS Lett (1994) 346:181-4. doi:10.1016/0014-5793(94)00463-3
102. Lett-Brown MA, Leonard EJ. Histamine-induced inhibition of normal human basophil chemotaxis to C5a. J Immunol (1977) 1950(118):815-8.
103. Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, et al. Modulation of the antitumor immune response by complement. Nat Immunol (2008) 9:1225-35. doi:10.1038/ni.1655
104. Nataf S, Davoust N, Ames RS, Barnum SR. Human T cells express the C5a receptor and are chemoattracted to C5a. J Immunol (1999) 1950(162):4018-23.
105. Ottonello L, Corcione A, Tortolina G, Airoldi I, Albesiano E, Favre A, et al. rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues. J Immunol (1999) 1950(162):6510-7.
106. Lalli PN, Strainic MG, Lin F, Medof ME, Heeger PS. Decay accelerating factor can control T cell differentiation into IFN-gamma-producing effector cells via regulating local C5a-induced IL-12 production. J Immunol (2007) 1950(179):5793-802. doi:10.4049/jimmunol.179.9.5793
107. Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M, Bless NM, et al. Protective effects of C5a blockade in sepsis. Nat Med (1999) 5:788-92. doi:10.1038/10512
108. Cortright DN, Meade R, Waters SM, Chenard BL, Krause JE. C5a, but not C3a, increases VEGF secretion in ARPE-19 human retinal pigment epithelial cells. Curr Eye Res (2009) 34:57-61. doi:10.1080/02713680802546658
109. Jain U, Cao Q, Thomas NA, Woodruff TM, Schwaeble WJ, Stover CM, et al. Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner. J Immunol (2015) 1950(194):3414-21. doi:10.4049/jimmunol.1401814
110. Cui W, Lapointe M, Gauvreau D, Kalant D, Cianflone K. Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation. Mol Immunol (2009) 46:3207-17. doi:10.1016/j.molimm.2009.08.013
111. Cain SA, Monk PN. The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J Biol Chem (2002) 277:7165-9. doi:10.1074/jbc. C100714200
112. Okinaga S, Slattery D, Humbles A, Zsengeller Z, Morteau O, Kinrade MB, et al. C5L2, a nonsignaling C5A binding protein. Biochemistry (2003) 42:9406-15. doi:10.1021/bi034489v
113. Bamberg CE, Mackay CR, Lee H, Zahra D, Jackson J, Lim YS, et al. The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. J Biol Chem (2010) 285:7633-44. doi:10.1074/jbc. M109.092106
114. Wang R, Lu B, Gerard C, Gerard NP. Disruption of the complement anaphylatoxin receptor C5L2 exacerbates inflammation in allergic contact dermatitis. J Immunol (2013) 1950(191):4001-9. doi:10.4049/jimmunol.1301626
115. Gerard NP, Lu B, Liu P, Craig S, Fujiwara Y, Okinaga S, et al. An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. J Biol Chem (2005) 280:39677-80. doi:10.1074/jbc. C500287200
116. Vijayan S, Asare Y, Grommes J, Soehnlein O, Lutgens E, Shagdarsuren G, et al. High expression of C5L2 correlates with high proinflammatory cytokine expression in advanced human atherosclerotic plaques. Am J Pathol (2014) 184:2123-33. doi:10.1016/j.ajpath.2014.04.004
117. Poursharifi P, Lapointe M, Pétrin D, Devost D, Gauvreau D, Hébert TE, et al. C5L2 and C5aR interaction in adipocytes and macrophages: insights into adipoimmunology. Cell Signal (2013) 25:910-8. doi:10.1016/j.cellsig.2012.12.010
118. Hsu W-C, Yang F-C, Lin C-H, Hsieh S-L, Chen N-J. C5L2 is required for C5a-triggered receptor internalization and ERK signaling. Cell Signal (2014) 26:1409-19. doi:10.1016/j.cellsig.2014.02.021
119. DeFea KA, Zalevsky J, Thoma MS, Déry O, Mullins RD, Bunnett NW. beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol (2000) 148:1267-81. doi:10.1083/jcb.148.6.1267
120. DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK. β-arrestins and cell signaling. Annu Rev Physiol (2007) 69:483-510. doi:10.1146/annurev.physiol.69.022405.154749
121. Zhang X, Kimura Y, Fang C, Zhou L, Sfyroera G, Lambris JD, et al. Regulation of toll-like receptor-mediated inflammatory response by complement in vivo. Blood (2007) 110:228-36. doi:10.1182/blood-2006-12-063636
122. Harokopakis E, Albzreh MH, Martin MH, Hajishengallis G. TLR2 transmodulates monocyte adhesion and transmigration via Rac1-and PI3K-mediated inside-out signaling in response to Porphyromonas gingivalis fimbriae. J Immunol (2006) 1950(176):7645-56. doi:10.4049/jimmunol.176.12.7645
123. Kagan JC, Medzhitov R. Phosphoinositide-mediated adaptor recruitment controls toll-like receptor signaling. Cell (2006) 125:943-55. doi:10.1016/j.cell.2006.03.047
124. Koleva M, Schlaf G, Landmann R, Götze O, Jungermann K, Schieferdecker HL. Induction of anaphylatoxin C5a receptors in rat hepatocytes by lipopolysaccharide in vivo: mediation by interleukin-6 from kupffer cells. Gastroenterology (2002) 122:697-708. doi:10.1053/gast.2002.31883
125. Hawlisch H, Belkaid Y, Baelder R, Hildeman D, Gerard C, Köhl J. C5a negatively regulates toll-like receptor 4-induced immune responses. Immunity (2005) 22:415-26. doi:10.1016/j.immuni.2005.02.006
126. Rudilla F, Fayolle C, Casares N, Durantez M, Arribillaga L, Lozano T, et al. Combination of a TLR4 ligand and anaphylatoxin C5a for the induction of antigen-specific cytotoxic T cell responses. Vaccine (2012) 30:2848-58. doi:10.1016/j.vaccine.2012.02.052
127. Zaal A, Lissenberg-Thunnissen SN, van Schijndel G, Wouters D, van Ham SM, ten Brinke A. Crosstalk between toll like receptors and C5a receptor in human monocyte derived DCs suppress inflammatory cytokine production. Immunobiology (2013) 218:175-80. doi:10.1016/j.imbio.2012.02.014
128. Pepys MB. Role of complement in induction of antibody production in vivo effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. J Exp Med (1974) 140:126-45. doi:10.1084/jem.140.1.126
129. Pepys MB, Butterworth AE. Inhibition by C3 fragments of C3-dependent rosette formation and antigen-induced lymphocyte transformation. Clin Exp Immunol (1974) 18:273-82.
130. Matsumoto AK, Martin DR, Carter RH, Klickstein LB, Ahearn JM, Fearon DT. Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. J Exp Med (1993) 178:1407-17. doi:10.1084/jem.178.4.1407
131. Cherukuri A, Cheng PC, Pierce SK. The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. J Immunol (2001) 1950(167):163-72. doi:10.4049/jimmunol.167.1.163
132. Klaus GG, Humphrey JH. A re-evaluation of the role of C3 in B-cell activation. Immunol Today (1986) 7:163-5. doi:10.1016/0167-5699(86)90165-9
133. Fang Y, Xu C, Fu Y-X, Holers VM, Molina H. Expression of complement receptors 1 and 2 on follicular dendritic cells is necessary for the generation of a strong antigen-specific IgG response. J Immunol (1998) 160:5273-9.
134. 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. doi:10.1126/science.271.5247.348
135. Brodeur SR, Angelini F, Bacharier LB, Blom AM, Mizoguchi E, Fujiwara H, et al. C4b-binding protein (C4BP) activates B cells through the CD40 receptor. Immunity (2003) 18:837-48. doi:10.1016/S1074-7613(03)00149-3
136. Chatterjee P, Agyemang AF, Alimzhanov MB, Degn S, Tsiftsoglou SA, Alicot E, et al. Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner. Eur J Immunol (2013) 43:2441-50. doi:10.1002/eji.201343412
137. Del Nagro CJ, Kolla RV, Rickert RC. A critical role for complement C3d and the B cell coreceptor (CD19/CD21) complex in the initiation of inflammatory arthritis. J Immunol (2005) 175:5379-89. doi:10.4049/jimmunol.175.8.5379
138. Lyubchenko T, Dal Porto JM, Holers VM, Cambier JC. Cutting edge: complement (C3d)-linked antigens break B cell anergy. J Immunol (2007) 1950(179):2695-9. doi:10.4049/jimmunol.179.5.2695
139. Hundgeburth LC, Wunsch M, Rovituso D, Recks MS, Addicks K, Lehmann PV, et al. The complement system contributes to the pathology of experimental autoimmune encephalomyelitis by triggering demyelination and modifying the antigen-specific T and B cell response. Clin Immunol (2013) 146:155-64. doi:10.1016/j.clim.2012.12.007
140. Kemper C, Atkinson JP. T-cell regulation: with complements from innate immunity. Nat Rev Immunol (2007) 7:9-18. doi:10.1038/nri1994
141. Kemper C, Chan AC, Green JM, Brett KA, Murphy KM, Atkinson JP. Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature (2003) 421:388-92. doi:10.1038/nature01315
142. Morgan BP, Marchbank KJ, Longhi MP, Harris CL, Gallimore AM. Complement: central to innate immunity and bridging to adaptive responses. Immunol Lett (2005) 97:171-9. doi:10.1016/j.imlet.2004.11.010
143. Baudino L, Sardini A, Ruseva MM, Fossati-Jimack L, Cook HT, Scott D, et al. C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens. Proc Natl Acad Sci U S A (2014) 111:1503-8. doi:10.1073/pnas.1316877111
144. Mueller-Ortiz SL, Morales JE, Wetsel RA. The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis. J Immunol (2014) 193:1278-89. doi:10.4049/jimmunol.1302787
145. Kwan W, van der Touw W, Paz-Artal E, Li MO, Heeger PS. Signaling through C5a receptor and C3a receptor diminishes function of murine natural regulatory T cells. J Exp Med (2013) 210:257-68. doi:10.1084/jem.20121525
146. Strainic MG, Shevach EM, An F, Lin F, Medof ME. Absence of signaling into CD4+ cells via C3aR and C5aR enables autoinductive TGF-β1 signaling and induction of Foxp3+ regulatory T cells. Nat Immunol (2013) 14:162-71. doi:10.1038/ni.2499
147. Le Friec G, Sheppard D, Whiteman P, Karsten CM, Shamoun SA-T, Laing A, et al. The CD46-Jagged1 interaction is critical for human TH1 immunity. Nat Immunol (2012) 13:1213-21. doi:10.1038/ni.2454
148. Ghannam A, Pernollet M, Fauquert J-L, Monnier N, Ponard D, Villiers M-B, et al. Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells. J Immunol (2008) 1950(181):5158-66. doi:10.4049/jimmunol.181.7.5158
149. Kolev M, Le Friec G, Kemper C. The role of complement in CD4+ T cell homeostasis and effector functions. Semin Immunol (2013) 25:12-9. doi:10.1016/j.smim.2013.04.012
150. Cardone J, Le Friec G, Vantourout P, Roberts A, Fuchs A, Jackson I, et al. Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nat Immunol (2010) 11:862-71. doi:10.1038/ni.1917
151. Heeger PS, Lalli PN, Lin F, Valujskikh A, Liu J, Muqim N, et al. Decay-accelerating factor modulates induction of T cell immunity. J Exp Med (2005) 201:1523-30. doi:10.1084/jem.20041967
152. Liu J, Miwa T, Hilliard B, Chen Y, Lambris JD, Wells AD, et al. The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. J Exp Med (2005) 201:567-77. doi:10.1084/jem.20040863
153. Dunkelberger JR, Song W-C. Complement and its role in innate and adaptive immune responses. Cell Res (2009) 20:34-50. doi:10.1038/cr.2009.139
154. Lipp AM, Juhasz K, Paar C, Ogris C, Eckerstorfer P, Thuenauer R, et al. Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in jurkat T cells. PLoS One (2014) 9:e85934. doi:10.1371/journal.pone.0085934
155. Wagner C, Ochmann C, Schoels M, Giese T, Stegmaier S, Richter R, et al. The complement receptor 1, CR1 (CD35), mediates inhibitory signals in human T-lymphocytes. Mol Immunol (2006) 43:643-51. doi:10.1016/j.molimm.2005.04.006
156. Tam JCH, Bidgood SR, McEwan WA, James LC. Intracellular sensing of complement C3 activates cell autonomous immunity. Science (2014) 345:1256070. doi:10.1126/science.1256070
157. Lambris JD, Ricklin D, Geisbrecht BV. Complement evasion by human pathogens. Nat Rev Microbiol (2008) 6:132-42. doi:10.1038/nrmicro1824
158. Zipfel PF, Würzner R, Skerka C. Complement evasion of pathogens: common strategies are shared by diverse organisms. Mol Immunol (2007) 44:3850-7. doi:10.1016/j.molimm.2007.06.149
159. Schneider MC, Exley RM, Chan H, Feavers I, Kang Y-H, Sim RB, et al. Functional significance of factor H binding to Neisseria meningitidis. J Immunol (2006) 176:7566-75. doi:10.4049/jimmunol.176.12.7566
160. Berggård K, Johnsson E, Mooi FR, Lindahl G. Bordetella pertussis binds the human complement regulator C4BP: role of filamentous hemagglutinin. Infect Immun (1997) 65:3638-43.
161. Ho DK, Skurnik M, Blom AM, Meri S. Yersinia pestis ail recruitment of C4b-binding protein leads to factor I-mediated inactivation of covalently and noncovalently bound C4b: immunity to infection. Eur J Immunol (2014) 44:742-51. doi:10.1002/eji.201343552
162. Lewis LA, Ngampasutadol J, Wallace R, Reid JEA, Vogel U, Ram S. The meningococcal vaccine candidate neisserial surface protein A (NspA) binds to factor H and enhances meningococcal resistance to complement. PLoS Pathog (2010) 6:e1001027. doi:10.1371/journal.ppat.1001027
163. Ermert D, Weckel A, Agarwal V, Frick I-M, Björck L, Blom AM. Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells. J Biol Chem (2013) 288:32172-83. doi:10.1074/jbc. M113.502955
164. Bhattacharjee A, Oeemig JS, Kolodziejczyk R, Meri T, Kajander T, Lehtinen MJ, et al. Structural basis for complement evasion by lyme disease pathogen Borrelia burgdorferi. J Biol Chem (2013) 288:18685-95. doi:10.1074/jbc. M113.459040
165. Meri T, Amdahl H, Lehtinen MJ, Hyvärinen S, McDowell JV, Bhattacharjee A, et al. Microbes bind complement inhibitor factor H via a common site. PLoS Pathog (2013) 9:e1003308. doi:10.1371/journal.ppat.1003308
166. Ngampasutadol J, Ram S, Gulati S, Agarwal S, Li C, Visintin A, et al. Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion. J Immunol (2008) 1950(180):3426-35. doi:10.4049/jimmunol.180.5.3426
167. Schneider MC, Prosser BE, Caesar JJE, Kugelberg E, Li S, Zhang Q, et al. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature (2009) 458:890-3. doi:10.1038/nature07769
168. Miller DP, Bell JK, McDowell JV, Conrad DH, Burgner JW, Héroux A, et al. Structure of factor H-binding protein B (FhbB) of the periopathogen, Treponema denticola. J Biol Chem (2012) 287:12715-22. doi:10.1074/jbc. M112.339721
169. Foster TJ. Immune evasion by Staphylococci. Nat Rev Microbiol (2005) 3:948-58. doi:10.1038/nrmicro1289
170. Hair PS, Foley CK, Krishna NK, Nyalwidhe JO, Geoghegan JA, Foster TJ, et al. Complement regulator C4BP binds to Staphylococcus aureus surface proteins SdrE and Bbp inhibiting bacterial opsonization and killing. Results Immunol (2013) 3:114-21. doi:10.1016/j.rinim.2013.10.004
171. Sharp JA, Echague CG, Hair PS, Ward MD, Nyalwidhe JO, Geoghegan JA, et al. Staphylococcus aureus surface protein SdrE binds complement regulator factor H as an immune evasion tactic. PLoS One (2012) 7:e38407. doi:10.1371/journal.pone.0038407
172. Liszewski MK, Leung MK, Hauhart R, Buller RML, Bertram P, Wang X, et al. Structure and regulatory profile of the monkeypox inhibitor of complement: comparison to homologs in vaccinia and variola and evidence for dimer formation. J Immunol (2006) 176:3725-34. doi:10.4049/jimmunol.176.6.3725
173. Lubinski JM, Wang L, Soulika AM, Burger R, Wetsel RA, Colten H, et al. Herpes simplex virus type 1 glycoprotein gC mediates immune evasion in vivo. J Virol (1998) 72:8257-63.
174. Rooijakkers SHM, van Strijp JAG. Bacterial complement evasion. Mol Immunol (2007) 44:23-32. doi:10.1016/j.molimm.2006.06.011
175. Fraga TR, Courrol DDS, Castiblanco-Valencia MM, Hirata IY, Vasconcellos SA, Juliano L, et al. Immune evasion by pathogenic Leptospira strains: the secretion of proteases that directly cleave complement proteins. J Infect Dis (2014) 209:876-86. doi:10.1093/infdis/jit569
176. Rooijakkers SHM, van Wamel WJB, Ruyken M, van Kessel KPM, van Strijp JAG. Anti-opsonic properties of staphylokinase. Microbes Infect (2005) 7:476-84. doi:10.1016/j.micinf.2004.12.014
177. Jusko M, Potempa J, Kantyka T, Bielecka E, Miller HK, Kalinska M, et al. Staphylococcal proteases aid in evasion of the human complement system. J Innate Immun (2014) 6:31-46. doi:10.1159/000351458
178. Laarman AJ, Ruyken M, Malone CL, van Strijp JAG, Horswill AR, Rooijakkers SHM. Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to mediate immune evasion. J Immunol (2011) 1950(186):6445-53. doi:10.4049/jimmunol.1002948
179. Del Tordello E, Vacca I, Ram S, Rappuoli R, Serruto D. Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum. Proc Natl Acad Sci U S A (2014) 111:427-32. doi:10.1073/pnas.1321556111
180. Agarwal S, Vasudhev S, DeOliveira RB, Ram S. Inhibition of the classical pathway of complement by meningococcal capsular polysaccharides. J Immunol (2014) 193:1855-63. doi:10.4049/jimmunol.1303177
181. Johnson JB, Borisevich V, Rockx B, Parks GD. A novel factor I activity in Nipah virus inhibits human complement pathways through cleavage of C3b. J Virol (2015) 89:989-98. doi:10.1128/JVI.02427-14
182. Hammel M, Sfyroera G, Ricklin D, Magotti P, Lambris JD, Geisbrecht BV. A structural basis for complement inhibition by Staphylococcus aureus. Nat Immunol (2007) 8:430-7. doi:10.1038/ni1450
183. Haspel N, Ricklin D, Geisbrecht BV, Kavraki LE, Lambris JD. Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d. Protein Sci (2008) 17:1894-906. doi:10.1110/ps.036624.108
184. Koch TK, Reuter M, Barthel D, Böhm S, van den Elsen J, Kraiczy P, et al. Staphylococcus aureus proteins Sbi and Efb recruit human plasmin to degrade complement C3 and C3b. PLoS One (2012) 7:e47638. doi:10.1371/journal.pone.0047638
185. Lee LYL, Liang X, Hook M, Brown EL. Identification and characterization of the C3 binding domain of the Staphylococcus aureus extracellular fibrinogen-binding protein (Efb). J Biol Chem (2004) 279:50710-6. doi:10.1074/jbc. M408570200
186. Lee LY, Höök M, Haviland D, Wetsel RA, Yonter EO, Syribeys P, et al. Inhibition of complement activation by a secreted Staphylococcus aureus protein. J Infect Dis (2004) 190:571-9. doi:10.1086/422259
187. Hammel M, Sfyroera G, Pyrpassopoulos S, Ricklin D, Ramyar KX, Pop M, et al. Characterization of Ehp, a secreted complement inhibitory protein from Staphylococcus aureus. J Biol Chem (2007) 282:30051-61. doi:10.1074/jbc. M704247200
188. Haupt K, Reuter M, van den Elsen J, Burman J, Hälbich S, Richter J, et al. The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement factor H and C3b. PLoS Pathog (2008) 4:e1000250. doi:10.1371/journal.ppat.1000250
189. Upadhyay A, Burman JD, Clark EA, Leung E, Isenman DE, van den Elsen JMH, et al. Structure-function analysis of the C3 binding region of Staphylococcus aureus immune subversion protein Sbi. J Biol Chem (2008) 283:22113-20. doi:10.1074/jbc. M802636200
190. Jongerius I, Köhl J, Pandey MK, Ruyken M, van Kessel KPM, van Strijp JAG, et al. Staphylococcal complement evasion by various convertase-blocking molecules. J Exp Med (2007) 204:2461-71. doi:10.1084/jem.20070818
191. Garcia BL, Ramyar KX, Tzekou A, Ricklin D, McWhorter WJ, Lambris JD, et al. Molecular basis for complement recognition and inhibition determined by crystallographic studies of the staphylococcal complement inhibitor (SCIN) bound to C3c and C3b. J Mol Biol (2010) 402:17-29. doi:10.1016/j.jmb.2010.07.029
192. Garcia BL, Ramyar KX, Ricklin D, Lambris JD, Geisbrecht BV. Advances in understanding the structure, function, and mechanism of the SCIN and Efb families of staphylococcal immune evasion proteins. Adv Exp Med Biol (2012) 946:113-33. doi:10.1007/978-1-4614-0106-3_7
193. Ricklin D, Tzekou A, Garcia BL, Hammel M, McWhorter WJ, Sfyroera G, et al. A molecular insight into complement evasion by the staphylococcal complement inhibitor protein family. J Immunol (2009) 1950(183):2565-74. doi:10.4049/jimmunol.0901443
194. Rooijakkers SHM, Wu J, Ruyken M, van Domselaar R, Planken KL, Tzekou A, et al. Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nat Immunol (2009) 10:721-7. doi:10.1038/ni.1756
195. Jongerius I, Puister M, Wu J, Ruyken M, van Strijp JAG, Rooijakkers SHM. Staphylococcal complement inhibitor modulates phagocyte responses by dimerization of convertases. J Immunol (2010) 1950(184):420-5. doi:10.4049/jimmunol.0902865
196. Ricklin D, Lambris JD. Compstatin: a complement inhibitor on its way to clinical application. Adv Exp Med Biol (2008) 632:273-92. doi:10.1111/eci.12419
197. Serruto D, Rappuoli R, Scarselli M, Gros P, van Strijp JAG. Molecular mechanisms of complement evasion: learning from staphylococci and meningococci. Nat Rev Microbiol (2010) 8:393-9. doi:10.1038/nrmicro2366
198. Leffler J, Bengtsson AA, Blom AM. The complement system in systemic lupus erythematosus: an update. Ann Rheum Dis (2014) 73:1601-6. doi:10.1136/annrheumdis-2014-205287
199. Schejbel L, Skattum L, Hagelberg S, Åhlin A, Schiller B, Berg S, et al. Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations. Genes Immun (2011) 12:626-34. doi:10.1038/gene.2011.39
200. Yin Y, Wu X, Shan G, Zhang X. Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis: a meta-analysis. Lupus (2012) 21:1088-97. doi:10.1177/0961203312451202
201. Vanhecke D, Roumenina LT, Wan H, Osthoff M, Schaller M, Trendelenburg M. Identification of a major linear C1q epitope allows detection of systemic lupus erythematosus anti-C1q antibodies by a specific peptide-based enzyme-linked immunosorbent assay. Arthritis Rheum (2012) 64:3706-14. doi:10.1002/art.34605
202. Radanova M, Vasilev V, Deliyska B, Kishore U, Ikonomov V, Ivanova D. Anti-C1q autoantibodies specific against the globular domain of the C1qB-chain from patient with lupus nephritis inhibit C1q binding to IgG and CRP. Immunobiology (2012) 217:684-91. doi:10.1016/j.imbio.2011.11.007
203. Mahler M, van Schaarenburg RA, Trouw LA. Anti-C1q autoantibodies, novel tests, and clinical consequences. Front Immunol (2013) 4:117. doi:10.3389/fimmu.2013.00117
204. Trouw LA, Groeneveld TWL, Seelen MA, Duijs JMGJ, Bajema IM, Prins FA, et al. Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J Clin Invest (2004) 114:679-88. doi:10.1172/JCI200421075
205. Bigler C, Schaller M, Perahud I, Osthoff M, Trendelenburg M. Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells. J Immunol (2009) 1950(183):3512-21. doi:10.4049/jimmunol.0803573
206. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med (2009) 361:1676-87. doi:10.1056/NEJMra0902814
207. Roumenina LT, Loirat C, Dragon-Durey M-A, Halbwachs-Mecarelli L, Sautes-Fridman C, Fremeaux-Bacchi V. Alternative complement pathway assessment in patients with atypical HUS. J Immunol Methods (2011) 365:8-26. doi:10.1016/j.jim.2010.12.020
208. Fakhouri F, Frémeaux-Bacchi V, Noël L-H, Cook HT, Pickering MC. C3 glomerulopathy: a new classification. Nat Rev Nephrol (2010) 6:494-9. doi:10.1038/nrneph.2010.85
209. Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis-a new look at an old entity. N Engl J Med (2012) 366:1119-31. doi:10.1056/NEJMra1108178
210. Malina M, Roumenina LT, Seeman T, Le Quintrec M, Dragon-Durey M-A, Schaefer F, et al. Genetics of hemolytic uremic syndromes. Presse Méd (2012) 1983(41):e105-14. doi:10.1016/j.lpm.2011.10.028
211. Ferreira VP, Herbert AP, Cortés C, McKee KA, Blaum BS, Esswein ST, et al. The binding of factor H to a complex of physiological polyanions and C3b on cells is impaired in atypical hemolytic uremic syndrome. J Immunol (2009) 1950(182):7009-18. doi:10.4049/jimmunol.0804031
212. Lehtinen MJ, Rops AL, Isenman DE, van der Vlag J, Jokiranta TS. Mutations of factor H impair regulation of surface-bound C3b by three mechanisms in atypical hemolytic uremic syndrome. J Biol Chem (2009) 284:15650-8. doi:10.1074/jbc. M900814200
213. Manuelian T, Hellwage J, Meri S, Caprioli J, Noris M, Heinen S, et al. Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome. J Clin Invest (2003) 111:1181-90. doi:10.1172/JCI200316651
214. Bienaime F, Dragon-Durey M-A, Regnier CH, Nilsson SC, Kwan WH, Blouin J, et al. Mutations in components of complement influence the outcome of factor I-associated atypical hemolytic uremic syndrome. Kidney Int (2010) 77:339-49. doi:10.1038/ki.2009.472
215. Nilsson SC, Kalchishkova N, Trouw LA, Fremeaux-Bacchi V, Villoutreix BO, Blom AM. Mutations in complement factor I as found in atypical hemolytic uremic syndrome lead to either altered secretion or altered function of factor I. Eur J Immunol (2010) 40:172-85. doi:10.1002/eji.200939280
216. Frémeaux-Bacchi V, Miller EC, Liszewski MK, Strain L, Blouin J, Brown AL, et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood (2008) 112:4948-52. doi:10.1182/blood-2008-01-133702
217. Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Arranz EA, et al. 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. doi:10.1073/pnas.0603420103
218. Marinozzi MC, Vergoz L, Rybkine T, Ngo S, Bettoni S, Pashov A, et al. Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign? J Am Soc Nephrol (2014) 25:2053-65. doi:10.1681/ASN.2013070796
219. Roumenina LT, Jablonski M, Hue C, Blouin J, Dimitrov JD, Dragon-Durey M-A, et al. Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome. Blood (2009) 114:2837-45. doi:10.1182/blood-2009-01-197640
220. Roumenina LT, Frimat M, Miller EC, Provot F, Dragon-Durey M-A, Bordereau P, et al. A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function. Blood (2012) 119:4182-91. doi:10.1182/blood-2011-10-383281
221. Schramm EC, Roumenina LT, Rybkine T, Chauvet S, Vieira-Martins P, Hue C, et al. Functional mapping of the interactions between complement C3 and regulatory proteins using atypical hemolytic uremic syndrome-associated mutations. Blood (2015) 125(15):2359-69. doi:10.1182/blood-2014-10-609073
222. Dragon-Durey M-A, Loirat C, Cloarec S, Macher M-A, Blouin J, Nivet H, et al. Anti-factor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol (2005) 16:555-63. doi:10.1681/ASN.2004050380
223. Dragon-Durey M-A, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B, et al. Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol (2010) 21:2180-7. doi:10.1681/ASN.2010030315
224. Józsi M, Licht C, Strobel S, Zipfel SLH, Richter H, Heinen S, et al. Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood (2008) 111:1512-4. doi:10.1182/blood-2007-09-109876
225. Blanc C, Roumenina LT, Ashraf Y, Hyvärinen S, Sethi SK, Ranchin B, et al. Overall neutralization of complement factor H by autoantibodies in the acute phase of the autoimmune form of atypical hemolytic uremic syndrome. J Immunol (2012) 1950(189):3528-37. doi:10.4049/jimmunol.1200679
226. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey M-A, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol (2013) 8:554-62. doi:10.2215/CJN.04760512
227. Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol (2010) 5:1844-59. doi:10.2215/CJN.02210310
228. Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, et al. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol (2013) 24:475-86. doi:10.1681/ASN.2012090884
229. Lemaire M, Frémeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet (2013) 45:531-6. doi:10.1038/ng.2590
230. Bruneau S, Néel M, Roumenina LT, Frimat M, Laurent L, Frémeaux-Bacchi V, et al. Loss of DGKe induces endothelial cell activation and death independently of complement activation. Blood (2014) 125(6):1038-46. doi:10.1182/blood-2014-06-579953
231. Rodríguez de Córdoba S, Hidalgo MS, Pinto S, Tortajada A. Genetics of atypical hemolytic uremic syndrome (aHUS). Semin Thromb Hemost (2014) 40:422-30. doi:10.1055/s-0034-1375296
232. Sansbury FH, Cordell HJ, Bingham C, Bromilow G, Nicholls A, Powell R, et al. Factors determining penetrance in familial atypical haemolytic uraemic syndrome. J Med Genet (2014) 51:756-64. doi:10.1136/jmedgenet-2014-102498
233. Frimat M, Tabarin F, Dimitrov JD, Poitou C, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, et al. Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome. Blood (2013) 122:282-92. doi:10.1182/blood-2013-03-489245
234. Pawluczkowycz AW, Lindorfer MA, Waitumbi JN, Taylor RP. Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential implications for the pathogenesis of anemia in malaria. J Immunol (2007) 1950(179):5543-52. doi:10.4049/jimmunol.179.8.5543
235. Dragon-Durey M-A, Blanc C, Marinozzi MC, van Schaarenburg RA, Trouw LA. Autoantibodies against complement components and functional consequences. Mol Immunol (2013) 56:213-21. doi:10.1016/j.molimm.2013.05.009
236. Paixão-Cavalcante D, López-Trascasa M, Skattum L, Giclas PC, Goodship TH, de Córdoba SR, et al. Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation. Kidney Int (2012) 82:1084-92. doi:10.1038/ki.2012.250
237. Servais A, Noël L-H, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey M-A, et al. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int (2012) 82:454-64. doi:10.1038/ki.2012.63
238. Martínez-Barricarte R, Heurich M, Valdes-Cañedo F, Vazquez-Martul E, Torreira E, Montes T, et al. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest (2010) 120:3702-12. doi:10.1172/JCI43343
239. Zhang Y, Meyer NC, Wang K, Nishimura C, Frees K, Jones M, et al. Causes of alternative pathway dysregulation in dense deposit disease. Clin J Am Soc Nephrol (2012) 7:265-74. doi:10.2215/CJN.07900811
240. Chen Q, Wiesener M, Eberhardt HU, Hartmann A, Uzonyi B, Kirschfink M, et al. Complement factor H-related hybrid protein deregulates complement in dense deposit disease. J Clin Invest (2014) 124:145-55. doi:10.1172/JCI71866
241. Goicoechea de Jorge E, Caesar JJE, Malik TH, Patel M, Colledge M, Johnson S, et al. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proc Natl Acad Sci U S A (2013) 110:4685-90. doi:10.1073/pnas.1219260110
242. Malik TH, Lavin PJ, Goicoechea de Jorge E, Vernon KA, Rose KL, Patel MP, et al. A hybrid CFHR3-1 gene causes familial C3 glomerulopathy. J Am Soc Nephrol (2012) 23:1155-60. doi:10.1681/ASN.2012020166
243. Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, Hadjisavvas A, McLean AG, et al. Identification of a mutation in complement factor H-related protein 5 in patients of cypriot origin with glomerulonephritis. Lancet (2010) 376:794-801. doi:10.1016/S0140-6736(10)60670-8
244. Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science (2005) 308:421-4. doi:10.1126/science.1110189
245. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A (2005) 102:7227-32. doi:10.1073/pnas.0501536102
246. Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science (2005) 308:419-21. doi:10.1126/science.1110359
247. Klein RJ, Zeiss C, Chew EY, Tsai J-Y, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science (2005) 308:385-9. doi:10.1126/science.1109557
248. Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet (2012) 379:1728-38. doi:10.1016/S0140-6736(12)60282-7
249. Shaw PX, Zhang L, Zhang M, Du H, Zhao L, Lee C, et al. Complement factor H genotypes impact risk of age-related macular degeneration by interaction with oxidized phospholipids. Proc Natl Acad Sci U S A (2012) 109:13757-62. doi:10.1073/pnas.1121309109
250. Weismann D, Hartvigsen K, Lauer N, Bennett KL, Scholl HPN, Charbel Issa P, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature (2011) 478:76-81. doi:10.1038/nature10449
251. Seddon JM, Yu Y, Miller EC, Reynolds R, Tan PL, Gowrisankar S, et al. Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat Genet (2013) 45:1366-70. doi:10.1038/ng.2741
252. Skerka C, Chen Q, Fremeaux-Bacchi V, Roumenina LT. Complement factor H related proteins (CFHRs). Mol Immunol (2013) 56:170-80. doi:10.1016/j.molimm.2013.06.001
253. Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat Genet (2006) 38:1173-7. doi:10.1038/ng1890
254. Fritsche LG, Lauer N, Hartmann A, Stippa S, Keilhauer CN, Oppermann M, et al. An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD). Hum Mol Genet (2010) 19:4694-704. doi:10.1093/hmg/ddq399
255. Tortajada A, Yébenes H, Abarrategui-Garrido C, Anter J, García-Fernández JM, Martínez-Barricarte R, et al. C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. J Clin Invest (2013) 123:2434-46. doi:10.1172/JCI68280
256. Cho MS, Vasquez HG, Rupaimoole R, Pradeep S, Wu S, Zand B, et al. Autocrine effects of tumor-derived complement. Cell Rep (2014) 6:1085-95. doi:10.1016/j.celrep.2014.02.014
257. Corrales L, Ajona D, Rafail S, Lasarte JJ, Riezu-Boj JI, Lambris JD, et al. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J Immunol (2012) 1950(189):4674-83. doi:10.4049/jimmunol.1201654
258. Vadrevu SK, Chintala NK, Sharma SK, Sharma P, Cleveland C, Riediger L, et al. Complement C5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche. Cancer Res (2014) 74:3454-65. doi:10.1158/0008-5472.CAN-14-0157
259. Surace L, Lysenko V, Fontana AO, Cecconi V, Janssen H, Bicvic A, et al. Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response. Immunity (2015) 42:767-77. doi:10.1016/j.immuni.2015.03.009
260. Ajona D, Castaño Z, Garayoa M, Zudaire E, Pajares MJ, Martinez A, et al. Expression of complement factor H by lung cancer cells: effects on the activation of the alternative pathway of complement. Cancer Res (2004) 64:6310-8. doi:10.1158/0008-5472.CAN-03-2328
261. Cui T, Chen Y, Knösel T, Yang L, Zöller K, Galler K, et al. Human complement factor H is a novel diagnostic marker for lung adenocarcinoma. Int J Oncol (2011) 39:161-8. doi:10.3892/ijo.2011.1010
262. Kinders R, Jones T, Root R, Bruce C, Murchison H, Corey M, et al. Complement factor H or a related protein is a marker for transitional cell cancer of the bladder. Clin Cancer Res (1998) 4:2511-20.
263. Riihilä PM, Nissinen LM, Ala-aho R, Kallajoki M, Grénman R, Meri S, et al. Complement factor H: a biomarker for progression of cutaneous squamous cell carcinoma. J Invest Dermatol (2014) 134:498-506. doi:10.1038/jid.2013.346
264. Santhekadur PK, Rajasekaran D, Siddiq A, Gredler R, Chen D, Schaus SE, et al. The transcription factor LSF: a novel oncogene for hepatocellular carcinoma. Am J Cancer Res (2012) 2:269-85.
265. Amornsiripanitch N, Hong S, Campa MJ, Frank MM, Gottlin EB, Patz EF. Complement factor H autoantibodies are associated with early stage NSCLC. Clin Cancer Res (2010) 16:3226-31. doi:10.1158/1078-0432.CCR-10-0321
266. Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, et al. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell (2015) 160:700-14. doi:10.1016/j.cell.2015.01.004
267. Riihilä P, Nissinen L, Farshchian M, Kivisaari A, Ala-Aho R, Kallajoki M, et al. Complement factor I promotes progression of cutaneous squamous cell carcinoma. J Invest Dermatol (2015) 135:579-88. doi:10.1038/jid.2014.376
268. Arkwright PD, Riley P, Hughes SM, Alachkar H, Wynn RF. Successful cure of C1q deficiency in human subjects treated with hematopoietic stem cell transplantation. J Allergy Clin Immunol (2014) 133:265-7. doi:10.1016/j.jaci.2013.07.035
269. Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet (2012) 379:474-81. doi:10.1016/S0140-6736(11)60935-5
270. Mehta P, Norsworthy PJ, Hall AE, Kelly SJ, Walport MJ, Botto M, et al. SLE with C1q deficiency treated with fresh frozen plasma: a 10-year experience. Rheumatology (Oxford) (2010) 49:823-4. doi:10.1093/rheumatology/kep387
271. Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol (2009) 24:687-96. doi:10.1007/s00467-008-0964-1
272. Johnson S, Stojanovic J, Ariceta G, Bitzan M, Besbas N, Frieling M, et al. An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome. Pediatr Nephrol (2014) 29:1967-78. doi:10.1007/s00467-014-2817-4
273. Zuber J, Fakhouri F, Roumenina LT, Loirat C, Frémeaux-Bacchi V; French Study Group for aHUS/C3G. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol (2012) 8:643-57. doi:10.1038/nrneph.2012.214
274. Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med (2006) 355:1233-43. doi:10.1056/NEJMoa061648
275. Legendre CM, Licht C, Loirat C. Eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med (2013) 369:1379-80. doi:10.1056/NEJMc1308826
276. Nilsson B, Larsson R, Hong J, Elgue G, Ekdahl KN, Sahu A, et al. Compstatin inhibits complement and cellular activation in whole blood in two models of extracorporeal circulation. Blood (1998) 92:1661-7.
277. Risitano AM, Ricklin D, Huang Y, Reis ES, Chen H, Ricci P, et al. Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria. Blood (2014) 123:2094-101. doi:10.1182/blood-2013-11-536573
278. Zhang Y, Nester CM, Holanda DG, Marsh HC, Hammond RA, Thomas LJ, et al. Soluble CR1 therapy improves complement regulation in C3 glomerulopathy. J Am Soc Nephrol (2013) 24:1820-9. doi:10.1681/ASN.2013010045
279. Fridkis-Hareli M, Storek M, Mazsaroff I, Risitano AM, Lundberg AS, Horvath CJ, et al. Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases. Blood (2011) 118:4705-13. doi:10.1182/blood-2011-06-359646
280. Hebecker M, Alba-Domínguez M, Roumenina LT, Reuter S, Hyvärinen S, Dragon-Durey M-A, et al. An engineered construct combining complement regulatory and surface-recognition domains represents a minimal-size functional factor H. J Immunol (2013) 1950(191):912-21. doi:10.4049/jimmunol.1300269
281. Risitano AM, Notaro R, Pascariello C, Sica M, del Vecchio L, Horvath CJ, et al. The complement receptor 2/factor H fusion protein TT30 protects paroxysmal nocturnal hemoglobinuria erythrocytes from complement-mediated hemolysis and C3 fragment. Blood (2012) 119:6307-16. doi:10.1182/blood-2011-12-398792
282. Schmidt CQ, Bai H, Lin Z, Risitano AM, Barlow PN, Ricklin D, et al. Rational engineering of a minimized immune inhibitor with unique triple-targeting properties. J Immunol (2013) 1950(190):5712-21. doi:10.4049/jimmunol.1203548