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Immunologic Research
Published in: Immunologic Research 2-3/2013

01-07-2013 | Diagnosis of Autoimmunity

Complement and autoimmunity

Authors: Eleonora Ballanti, Carlo Perricone, Elisabetta Greco, Marta Ballanti, Gioia Di Muzio, Maria Sole Chimenti, Roberto Perricone

Published in: Immunologic Research | Issue 2-3/2013

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Abstract

The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren’s syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.
Literature
1.
Moffitt MC, Frank MM. Complement resistance in microbes. Springer Semin Immunopathol. 1994;15:327–44.PubMedCrossRef
2.
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.PubMedCrossRef
3.
4.
Hawlisch H, Köhl J. Complement and toll-like receptors: key regulators of adaptive immune responses. Mol Immunol. 2006;43:13–21.PubMedCrossRef
5.
6.
Nauta AJ, Castellano G, Xu W, Woltman AM, Borrias MC, Daha MR, et al. Opsonization with C1q and mannose-binding lectin targets apoptotic cells to dendritic cells. J Immunol. 2004;173:3044–50.PubMed
7.
Gál P, Dobó J, Závodszky P, Sim RB. Early complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions. Mol Immunol. 2009;46:2745–52.PubMedCrossRef
8.
Rus H, Cudrici C, Niculescu F. The role of the complement system in innate immunity. Immunol Res. 2005;33:103–12.PubMedCrossRef
9.
Liszewski MK, Farries TC, Lublin DM, Rooney IA, Atkinson JP. Control of the complement system. Adv Immunol. 1996;61:201–83.PubMedCrossRef
10.
Lindahl G, Sjöbring U, Johnsson E. Human complement regulators: a major target for pathogenic microorganisms. Curr Opin Immunol. 2000;12:44–51.PubMedCrossRef
11.
12.
Boccuni P, Del Vecchio L, Di Noto R, Rotoli B. Glycosyl phosphatidylinositol (GPI)-anchored molecules and the pathogenesis of paroxysmal nocturnal hemoglobinuria. Crit Rev Oncol Hematol. 2000;33:25–43.PubMedCrossRef
13.
Nauta AJ, Roos A, Daha MR. A regulatory role for complement in innate immunity and autoimmunity. Int Arch Allergy Immunol. 2004;134:310–23.PubMedCrossRef
14.
Théroux P, Martel C. Complement activity and pharmacological inhibition in cardiovascular disease. Can J Cardiol. 2006;22(Suppl B):18B–24B.PubMedCrossRef
15.
Rother KO, Till GO, Hansch GM. The complement system. 2nd ed. Berlin: Springer; 1998.CrossRef
16.
Kabat EA, Mayer MM. Experimental Immunochemistry. 2nd ed. Springfield, IL: Thomas; 1961.
17.
Sturfelt G, Truedsson L. Complement and its breakdown products in SLE. Rheumatology. 2005;44:1227–32.PubMedCrossRef
18.
Oppermann M, Baumgarten H, Brandt E, Gottsleben W, Kurts C, Götze O. Quantitation of components of the alternative pathway of complement (APC) by enzyme-linked immunosorbent assays. J Immunol Methods. 1990;133:181–90.PubMedCrossRef
19.
Klos A, Ihrig V, Messner M, Grabbe J, Bitter-Suermann D. Detection of native human complement components C3 and C5 and their primary activation peptides C3a and C5a (anaphylatoxic peptides) by ELISAs with monoclonal antibodies. J Immunol Methods. 1988;111:241–52.PubMedCrossRef
20.
Seino J, Warmold A, Wall Bake Lvd, van Es LA, Daha MR. A novel ELISA assay for the detection of C3 nephritic factor. J Immunol Methods. 1993;159:221–7.PubMedCrossRef
21.
Shoenfeld Y, Gershwin ME, Meroni PL. Autoantibodies. 2nd ed. Amsterdam: Elsevier; 2007.
22.
Thurman JM, Rohrer B. Noninvasive detection of complement activation through radiologic imaging. Adv Exp Med Biol. 2013;734:271–82.CrossRef
23.
Chen M, Daha MR, Kallenberg CG. The complement system in systemic autoimmune disease. J Autoimmun. 2010;34:J276–86.PubMedCrossRef
24.
Pettigrew HD, Teuber SS, Gershwin ME. Clinical significance of complement deficiencies. Ann N Y Acad Sci. 2009;1173:108–23.PubMedCrossRef
25.
26.
27.
Bussone G, Mouthon L. Autoimmune manifestations in primary immune deficiencies. Autoimmun Rev. 2009;8:332–6.PubMedCrossRef
28.
Pittoni V, Valesini G. The clearance of apoptotic cells: implications for autoimmunity. Autoimmun Rev. 2002;1:154–61.PubMedCrossRef
29.
Lu JH, Teh BK, Wang L, Wang YN, Tan YS, Lai MC, et al. The classical and regulatory functions of C1q in immunity and autoimmunity. Cell Mol Immunol. 2008;5:9–21.PubMedCrossRef
30.
Carroll MC. The role of complement in B cell activation and tolerance. Adv Immunol. 2000;74:61–88.PubMedCrossRef
31.
Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity. 2007;40:560–6.PubMedCrossRef
32.
Muñoz LE, Janko C, Schulze C, Schorn C, Sarter K, Schett G, et al. Autoimmunity and chronic inflammation—two clearance-related steps in the etiopathogenesis of SLE. Autoimmun Rev. 2010;10:38–42.PubMedCrossRef
33.
Csomor E, Bajtay Z, Sándor N, Kristóf K, Arlaud GJ, Thiel S, et al. Complement protein C1q induces maturation of human dendritic cells. Mol Immunol. 2007;44:3389–97.PubMedCrossRef
34.
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;188:5682–93.PubMedCrossRef
35.
Erdei A, Isaák A, Török K, Sándor N, Kremlitzka M, Prechl J, et al. Expression and role of CR1 and CR2 on B and T lymphocytes under physiological and autoimmune conditions. Mol Immunol. 2009;46:2767–73.PubMedCrossRef
36.
Marquart HV, Svendsen A, Rasmussen JM, Nielsen CH, Junker P, Svehag SE, et al. Complement receptor expression and activation of the complement cascade on B lymphocytes from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol. 1995;101:60–5.PubMedCrossRef
37.
Wilson JG, Ratnoff WD, Schur PH, Fearon DT. Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus. Arthritis Rheum. 1986;29:739–47.PubMedCrossRef
38.
Prokopec KE, Rhodiner M, Matt P, Lindqvist U, Kleinau S. Down regulation of Fc and complement receptors on B cells in rheumatoid arthritis. Clin Immunol. 2010;137:322–9.PubMedCrossRef
39.
Gualtierotti R, Biggioggero M, Penatti AE, Meroni PL. Updating on the pathogenesis of systemic lupus erythematosus. Autoimmun Rev. 2010;10:3–7.PubMedCrossRef
40.
Manderson AP, Botto M, Walport MJ. The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol. 2004;22:431–56.PubMedCrossRef
41.
Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ. Systemic lupus erythematosus, complement deficiency and apoptosis. Adv Immunol. 2000;76:227–324.PubMedCrossRef
42.
Biesecker G, Lavin L, Ziskind M, Koffler D. Cutaneous localization of the membrane attack complex in discoid and systemic lupus erythematosus. N Engl J Med. 1982;306:264–70.PubMedCrossRef
43.
Helm KF, Peters MS. Deposition of membrane attack complex in cutaneous lesions of lupus erythematosus. J Am Acad Dermatol. 1993;28:687–91.PubMedCrossRef
44.
Paronetto F, Koffler D. Immunofluorescent localization of immunoglobulins, complement, and fibrinogen in human diseases. I. Systemic lupus erythematosus. J Clin Invest. 1965;44:1657–64.PubMedCrossRef
45.
Lachmann PJ, Muller-Eberhard HJ, Kunkel HG, Paronetto F. The localization of in vivo bound complement in tissue section. J Exp Med. 1962;115:63–82.PubMedCrossRef
46.
Sciascia S, Ceberio L, Garcia-Fernandez C, Roccatello D, Karim Y, Cuadrado MJ. Systemic lupus erythematosus and infections: clinical importance of conventional and upcoming biomarkers. Autoimmun Rev. 2012;12:157–63.PubMedCrossRef
47.
48.
Ross GD, Yount WJ, Walport MJ, Winfield JB, Parker CJ, Fuller CR, et al. Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation. J Immunol. 1985;135:2005–14.PubMed
49.
Ballanti E, Perricone C, Di Muzio G, Kroegler B, Chimenti MS, Graceffa D, et al. Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationship with anti-TNF inhibitors. Autoimmun Rev. 2011;10:617–23.PubMedCrossRef
50.
Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977;146:857–68.PubMedCrossRef
51.
Courtenay JS, Dallman MJ, Dayan AD, Martin A, Mosedale B. Immunisation against heterologous type II collagen induces arthritis in mice. Nature. 1980;283:666–8.PubMedCrossRef
52.
Cathcart ES, Hayes KC, Gonnerman WA, Lazzari AA, Franzblau C. Experimental arthritis in a nonhuman primate. I. Induction by bovine type II collagen. Lab Invest. 1986;54:26–31.PubMed
53.
Yoo TJ, Kim SY, Stuart JM, Floyd RA, Olson GA, Cremer MA, et al. Induction of arthritis in monkeys by immunization with type II collagen. J Exp Med. 1988;168:777–82.PubMedCrossRef
54.
Hietala MA, Jonsson IM, Tarkowski A, Kleinau S, Pekna M. Complement deficiency ameliorates collagen-induced arthritis in mice. J Immunol. 2002;169:454–9.PubMed
55.
Wang Y, Rollins SA, Madri JA, Matis LA. Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease. Proc Natl Acad Sci USA. 1995;92:8955–9.PubMedCrossRef
56.
Mizuno M. A review of current knowledge of the complement system and the therapeutic opportunities in inflammatory arthritis. Curr Med Chem. 2006;13:1707–17.PubMedCrossRef
57.
D’Cruz D, Taylor J, Ahmed T, Asherson R, Khamashta M, Hughes GR. Complement factor 2 deficiency: a clinical and serological family study. Ann Rheum Dis. 1992;51:1254–6.PubMedCrossRef
58.
Di Muzio G, Perricone C, Ballanti E, Kroegler B, Greco E, Novelli L, et al. Complement system and rheumatoid arthritis: relationships with autoantibodies, serological, clinical features, and anti-TNF treatment. Int J Immunopathol Pharmacol. 2011;24:357–66.PubMed
59.
Miura N, Prentice HL, Scheider PM, Perlmutter DH. Synthesis and regulation of the two human complement C4 genes in stable transfected mouse fibroblasts. J Biol Chem. 1987;262:7298–305.PubMed
60.
Andus T, Heinrich PC, Bauer J, Trau-Thi TA, Decker K, Manuel D, et al. Discrimination of hepatocyte stimulating activity from human recombinant tumour necrosis factor a. Eur J lmmunol. 1988;17:1193–7.CrossRef
61.
Anthony R, EL-Omar E, Lappin DF, MacSween RNM, Whaley K. Regulation of hepatic synthesis of C3 and C4 during acute-phase response in the rat. Eur J Immunol. 1989;19:1405–12.PubMedCrossRef
62.
Ramadori G, Van Daume J, Riedert H, Mayer Zum Buschenfelde KH. Interleukin-6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse comparison as with interleukin-1β and tumour necrosis faclor-α. Eur J Immunol. 1988;18:1259–64.PubMedCrossRef
63.
Moffat GJ, Lappin D, Birnie GD, Whaley K. Complement biosynthesis in human synovial tissue. Clin Exp Immunol. 1989;78:54–60.PubMed
64.
Ruddy S, Colten HR. Rheumatoid arthritis. Biosynthesis of complement proteins by synovial tissues. N Engl J Med. 1974;290:1284–8.PubMedCrossRef
65.
Neumann E, Barnum SR, Tarner IH, Echols J, Fleck M, Judex M, et al. Local production of complement proteins in rheumatoid arthritis synovium. Arthritis Rheum. 2002;46:934–45.PubMedCrossRef
66.
Guc D, Gulati P, Lemercier C, Lappin D, Birnie GD, Whaley K. Expression of the components and regulatory proteins of the alternative complement pathway and the membrane attack complex in normal and diseased synovium. Rheumatol Int. 1993;13:139–46.PubMedCrossRef
67.
Whaley K, Guc D, Gulati P, Lappin D. Synthesis of complement components by synovial membrane. Immunopharmacology. 1992;24:83–9.PubMedCrossRef
68.
Doherty M, Richards N, Hornby J, Powell R. Relation between synovial fluid C3 degradation products and local joint inflammation in rheumatoid arthritis, osteoarthritis, and crystal associated arthropathy. Ann Rheum Dis. 1988;47:190–7.PubMedCrossRef
69.
Oleesky DA, Daniels RH, Williams BD, Amos N, Morgan BP. Terminal complement complexes and C1/C1 inhibitor complexes in rheumatoid arthritis and other arthritic conditions. Clin Exp Immunol. 1991;84:250–5.PubMed
70.
Konttinen YT, Ceponis A, Meri S, Vuorikoski A, Kortekangas P, Sorsa T, et al. Complement in acute and chronic arthritides: assessment of C3c, C9, and protectin (CD59) in synovial membrane. Ann Rheum Dis. 1996;55:888–94.PubMedCrossRef
71.
Jose PJ, Moss IK, Maini RN, Williams TJ. Measurement of the chemotactic complement fragment C5a in rheumatoid synovial fluids by radioimmunoassay: role of C5a in the acute inflammatory phase. Ann Rheum Dis. 1990;49:747–52.PubMedCrossRef
72.
Høgåsen K, Mollnes TE, Harboe M, Götze O, Hammer HB, Oppermann M. Terminal complement pathway activation and low lysis inhibitors in rheumatoid arthritis synovial fluid. J Rheumatol. 1995;22:24–8.PubMed
73.
Zubler RH, Nydegger U, Perrin LH, Fehr K, McCormick J, Lambert PH, et al. Circulating and intra-articular immune complexes in patients with rheumatoid arthritis: correlation of 125IClq binding activity with clinical and biological features of the disease. J Clin Invest. 1976;57:1308–19.PubMedCrossRef
74.
Hay FC, Nineham LJ, Perumal R, Roitt IM. Intra-articular and circulating immune complexes and antiglobulins (IgG and IgM) in rheumatoid arthritis: correlation with clinical features. Ann Rheum Dis. 1979;38:1–7.PubMedCrossRef
75.
Robbins DL, Fiegal DW Jr, Leek JC, Shapiro R, Wiesner K. Complement activation by 19S IgM rheumatoid factor: relationship to disease activity in rheumatoid arthritis. J Rheumatol. 1986;13:33–8.PubMed
76.
Sato Y, Sato R, Watanabe H, Kogure A, Watanabe K, Nishimaki T, et al. Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors. Ann Rheum Dis. 1993;52:795–800.PubMedCrossRef
77.
Sato Y, Watanabe H, Kogure A, Miyata M, Watanabe K, Nishimaki T, et al. Complement-activating properties of IgM rheumatoid factors reacting with IgG subclasses. Clin Rheumatol. 1995;14:425–8.PubMedCrossRef
78.
Tanimoto K, Cooper NR, Johnson JS, Vaughan JH. Complement fixation by rheumatoid factor. J Clin Invest. 1975;55:437–45.PubMedCrossRef
79.
Ruddy S, Austen KF. Activation of the complement and properdin systems in rheumatoid arthritis. Ann N Y Acad Sci. 1975;256:96–104.PubMedCrossRef
80.
El-Ghobarey A, Whaley K. Alternative pathway complement activation in rheumatoid arthritis. J Rheumatol. 1980;7:453–60.PubMed
81.
Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB. Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nat Med. 1995;1:237–43.PubMedCrossRef
82.
Trouw LA, Haisma EM, Levarht EW, van der Woude D, Ioan-Facsinay A, Daha MR, et al. Anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathways. Arthritis Rheum. 2009;60:1923–31.PubMedCrossRef
83.
Volonakis JE. Complement activation by C-reactive protein complexes. Ann N Y Acad Sci. 1982;389:235–49.CrossRef
84.
Wolbink GJ, Brouwer MC, Buysman S, ten Berge IJM, Hack CE. CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes. J Immunol. 1996;157:473–9.PubMed
85.
Wolbink GJ, Bossink AWJ, Groeneveld ABJ, de Groot MCM, Thijs LG, Hack CE. Complement activation in patients with sepsis is in part mediated by C-reactive protein. J Infect Dis. 1998;177:81–7.PubMedCrossRef
86.
Molenaar ET, Voskuyl AE, Familian A, van Mierlo GJ, Dijkmans BA, Hack CE. Complement activation in patients with rheumatoid arthritis mediated in part by C-reactive protein. Arthritis Rheum. 2001;44:997–1002.PubMedCrossRef
87.
Lagrand WK, Niessen HWM, Wolbink GJ, Jaspers LH, Visser CA, Verheugt FWA, et al. C-reactive protein co-localizes with complement in human hearts during acute myocardial infarction. Circulation. 1997;95:97–103.PubMedCrossRef
88.
Sjöberg A, Onnerfjord P, Mörgelin M, Heinegård D, Blom AM. The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q. J Biol Chem. 2005;280:32301–8.PubMedCrossRef
89.
Mollnes TE, Lea T, Mellbye OJ, Pahle J, Grand O, Harboe M. Complement activation in rheumatoid arthritis evaluated by C3dg and the terminal complement complex. Arthritis Rheum. 1986;29:715–21.PubMedCrossRef
90.
Olmez U, Garred P, Mollnes TE, Harboe M, Berntzen HB, Munthe E. C3 activation products, C3 containing immune complexes, the terminal complement complex and native C9 in patients with rheumatoid arthritis. Scand J Rheumatol. 1991;20:183–9.PubMedCrossRef
91.
Wouters D, Voskuyl AE, Molenaar ET, Dijkmans BA, Hack CE. Evaluation of classical complement pathway activation in rheumatoid arthritis: measurement of C1q–C4 complexes as novel activation products. Arthritis Rheum. 2006;54:1143–50.PubMedCrossRef
92.
Rosenberg EW, Noah PW, Wyatt RJ, Jones RM, Kolb WP. Complement activation in psoriasis. Clin Exp Dermatol. 1990;15:16–20.PubMedCrossRef
93.
Partsch G, Bauer K, Bröll H, Petera P, Dunky A, Merétey K. Complement C3 cleavage product in synovial fluids detected by immunofixation. Z Rheumatol. 1991;50:82–5.PubMed
94.
Triolo G, Accardo-Palumbo A, Sallì L, Ciccia F, Ferrante A, Tedesco L, et al. Impaired expression of erythrocyte glycosyl-phosphatidylinositol-anchored membrane CD59 in patients with psoriatic arthritis. Relation to terminal complement pathway activation. Clin Exp Rheumatol. 2003;21:225–8.PubMed
95.
Rivas D, Riestra-Noriega JL, Torre-Alonso JC, Rodriguez A, Gutiérrez C. Decrease in detectable complement receptor type 1 levels on erythrocytes from patients with psoriatic polyarthritis. Br J Rheumatol. 1994;33:626–30.PubMedCrossRef
96.
Chimenti MS, Perricone C, Graceffa D, Di Muzio G, Ballanti E, Guarino MD, et al. Complement system in psoriatic arthritis: a useful marker in response prediction and monitoring of anti-TNF treatment. Clin Exp Rheumatol. 2012;30:23–30.PubMed
97.
98.
Townes AS. Topics in clinical medicine. Complement’s levels in disease. Johns Hopkins Med J. 1967;120:337–9.PubMed
99.
Senaldi G, Lupoli S, Vergani D, Black CM. Activation of the complement system in systemic sclerosis. Relationship to clinical severity. Arthritis Rheum. 1989;32:1262–7.PubMedCrossRef
100.
Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980;23:581–90.CrossRef
101.
Valentini G, Della Rossa A, Bombardieri S, Bencivelli W, Silman AJ, D’Angelo S, et al. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis. 2001;60:592–8.PubMedCrossRef
102.
Hudson M, Walker JG, Fritzler M, Taillefer S, Canadian Scleroderma Research Group, Baron M. Hypocomplementemia in systemic sclerosis, clinical and serological correlations. J Rheumatol. 2007;34:1–6.
103.
Wetsel RA. Structure, function and cellular expression of complement anaphylatoxin receptors. Curr Opin Immunol. 1995;7:48–53.PubMedCrossRef
104.
Shin ML, Rus HG, Nicolescu FI. Membrane attack by complement: assembly and biology of terminal complement complexes. Biomembranes. 1996;4:123–49.
105.
Holers VM, Girardi G, Mo L, Guthridge JM, Molina H, Pierangeli SS, et al. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med. 2002;195:211–20.PubMedCrossRef
106.
Girardi G, et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003;112:1644–54.PubMed
107.
Kim YU, Kinoshita H, Molina H, Hourcade D, Esya L, Wagner M, et al. Mouse complement regulatory protein Crry/p65 utilizes the specific mechanisms of both decay-accelerating factor and membrane cofactor protein. J Exp Med. 1995;181:151–9.PubMedCrossRef
108.
Xu C, Mao D, Holers VM, Palanca B, Cheng A, Molina H. A critical role for the murine complement regulator Crry in fetomaternal tolerance. Science. 2000;287:498–501.PubMedCrossRef
109.
Nangaku M, Alpers CE, Pippin J, Shankland SJ, Kurokawa K, Adler S, et al. CD59 protects glomerular endothelial cells from immune-mediated thrombotic microangiopathy in rats. J Am Soc Nephrol. 1998;9:590–7.PubMed
110.
Pierangeli SS, Girardi G, Vega-Ostertag M, Liu X, Espinola RG, Salmon J. Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthritis Rheum. 2005;52:2120–4.PubMedCrossRef
111.
Salmon JE, Girardi G. Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation. J Reprod Immunol. 2008;77:51–6.PubMedCrossRef
112.
Oku K, Atsumi T, Bohgaki M, Amengual O, Kataoka H, Horita T, et al. Complement activation in patients with primary antiphospholipid syndrome. Ann Rheum Dis. 2009;68:1030–5.PubMedCrossRef
113.
Dalakas MC. Pathogenesis and therapies of immune-mediated myopathies. Autoimmun Rev. 2012;11:203–6.PubMedCrossRef
114.
115.
Kissel JT, Mendell JR, Rammohan KW. Microvascular deposition of complement membrane attack complex in dermatomyositis. N Engl J Med. 1986;314:329–34.PubMedCrossRef
116.
Mascaró JM Jr, Hausmann G, Herrero C, Grau JM, Cid MC, Palou J, et al. Membrane attack complex deposits in cutaneous lesions of dermatomyositis. Arch Dermatol. 1995;131:1386–92.PubMedCrossRef
117.
118.
Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM. Clinical evolution, and morbidity and mortality of primary Sjogren’s syndrome. Semin Arthritis Rheum. 2000;29:296–304.PubMedCrossRef
119.
Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren’s syndrome. Arthritis Rheum. 2002;46:741–7.PubMedCrossRef
120.
Theander E, Manthorpe R, Jacobsson LT. Mortality and causes of death in primary Sjogren’s syndrome: a prospective cohort study. Arthritis Rheum. 2004;50:1262–9.PubMedCrossRef
121.
Ramos-Casals M, Brito-Zeron P, Yague J, Akasbi M, Bautista R, Ruano M, et al. Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren’s syndrome. Rheumatology (Oxford). 2005;44:89–94.CrossRef
122.
Arnaud L, Haroche J, Mathian A, Gorochov G, Amoura Z. Pathogenesis of Takayasu’s arteritis: a 2011 update. Autoimmun Rev. 2011;11:61–7.PubMedCrossRef
123.
Seo P, Stone JH. The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med. 2004;117:39–50.PubMedCrossRef
124.
Kallenberg CGM. Pathophysiology of ANCA-associated small vessel vasculitis. Curr Rheumatol Rep. 2010;12:399–405.PubMedCrossRef
125.
Schreiber A, Xiao H, Jennette JC, Schneider W, Luft FC, Kettritz R. C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J Am Soc Nephrol. 2009;20:289–98.PubMedCrossRef
126.
Xiao H, Schreiber A, Heeringa P, Falk RJ, Jennette JC. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol. 2007;170:52–64.PubMedCrossRef
127.
Xing GQ, Chen M, Liu G, Heeringa P, Zhang JJ, Zheng X, et al. Complement activation is involved in renal damage in human antineutrophil cytoplasmic autoantibody associated pauci-immune vasculitis. J Clin Immunol. 2009;29:282–91.PubMedCrossRef
128.
Lospalluto J, Dorward B, Miller W Jr, Ziff M. Cryoglobulinemia based on interaction between a gamma macroglobulin and 7S gamma globulin. Am J Med. 1962;32:142–5.PubMedCrossRef
129.
130.
Monti G, Galli M, Invernizzi F, Pioltelli P, Saccardo F, Monteverde A, et al. Cryoglobulinaemias: a multi-centre study of the early clinical and laboratory manifestations of primary and secondary disease. GISC. Italian Group for the Study of Cryoglobulinaemias. QJM. 1995;88:115–26.PubMed
131.
Tarantino A, Anelli A, Costantino A, De Vecchi A, Monti G, Massaro L. Serum complement pattern in essential mixed cryoglobulinaemia. Clin Exp Immunol. 1978;32:77–85.PubMed
132.
Davin JC. Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy. Clin J Am Soc Nephrol. 2011;6:679–89.PubMedCrossRef
133.
Hisano S, Matsushita M, Fujita T, Iwasaki H. Activation of the lectin complement pathway in Henoch-Schonlein purpura nephritis. Am J Kidney Dis. 2005;45:295–302.PubMedCrossRef
134.
Roos A, Rastaldi MP, Calvaresi N, Oortwijn BD, Schlagwein N, van Gijlswijk-Janssen DJ, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol. 2006;17:1724–34.PubMedCrossRef
135.
Espinosa M, Ortega R, Gómez-Carrasco JM, López-Rubio F, López-Andreu M, López-Oliva MO, et al. Mesangial C4d deposition: a new prognostic factor in IgA nephropathy. Nephrol Dial Transplant. 2009;24:886–91.PubMedCrossRef
136.
Holers VM. The complement system as a therapeutic target in autoimmunity. Clin Immunol. 2003;107:140–51.PubMedCrossRef
137.
Makrides SC. Therapeutic inhibition of the complement system. Pharmacol Rev. 1998;50:59–87.PubMed
138.
Asghar SS, Pasch MC. Therapeutic inhibition of the complement system. Y2K update. Front Biosci. 2000;5:E63–81.PubMedCrossRef
139.
Goodfellow RM, Williams AS, Levin JL, Williams BD, Morgan BP. Soluble complement receptor one (sCR1) inhibits the development and progression of rat collagen-induced arthritis. Clin Exp Immunol. 2000;119:210–6.PubMedCrossRef
140.
Ames RS, Lee D, Foley JJ, Jurewicz AJ, Tornetta MA, Bautsch W, et al. Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models. J Immunol. 2001;166:6341–8.PubMed
141.
Woodruff TM, Strachan AJ, Dryburgh N, Shiels IA, Reid RC, Fairlie DP, et al. Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis Rheum. 2002;46:2476–85.PubMedCrossRef
142.
Fraser DA, Harris CL, Williams AS, Mizuno M, Gallagher S, Smith RA, et al. Generation of a recombinant, membrane-targeted form of the complement regulator CD59: activity in vitro and in vivo. J Biol Chem. 2003;278:48921–7.PubMedCrossRef
143.
Vergunst CE, Gerlag DM, Dinant H, Schulz L, Vinkenoog M, Smeets TJ, et al. Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology (Oxford). 2007;46:1773–8.CrossRef
144.
Wang Y, Hu Q, Madri JA, Rollins SA, Chodera A, Matis LA. Amelioration of lupus-like autoimmune disease in NZB/W F1 mice after treatment with a blocking monoclonal antibody specific for complement component C5. Proc Natl Acad Sci USA. 1996;93:8563–8.PubMedCrossRef
145.
Watanabe H, Garnier G, Circolo A, Wetsel RA, Ruiz P, Holers VM, et al. Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B. J Immunol. 2000;164:786–94.PubMed
146.
Bao L, Haas M, Boackle SA, Kraus DM, Cunningham PN, Park P, et al. Transgenic expression of a soluble complement inhibitor protects against renal disease and promotes survival in MRL/lpr mice. J Immunol. 2002;168:3601–7.PubMed
147.
Bao L, Haas M, Kraus DM, Hack BK, Rakstang JK, Holers VM, et al. Administration of a soluble recombinant complement C3 inhibitor protects against renal disease in MRL/lpr mice. J Am Soc Nephrol. 2003;14:670–9.PubMedCrossRef
148.
Murdaca G, Colombo BM, Puppo F. Emerging biological drugs: a new therapeutic approach for Systemic Lupus Erythematosus. An update upon efficacy and adverse events. Autoimmun Rev. 2011;11:56–60.PubMedCrossRef
149.
Parker CJ. Management of paroxysmal nocturnal hemoglobinuria in the era of complement inhibitory therapy. Hematology Am Soc Hematol Educ Program. 2011;2011:21–9.PubMedCrossRef
150.
Cicardi M, Zanichelli A. Replacement therapy with C1 esterase inhibitors for hereditary angioedema. Drugs Today. 2010;46:867–74.PubMedCrossRef
151.
Mollnes TE, Høgåsen K, De Carolis C, Vaquero E, Nielsen EW, Fontana L, et al. High-dose intravenous immunoglobulin treatment activates complement in vivo. Scand J Immunol. 1998;48:312–7.PubMedCrossRef
152.
Morgan BP, Harris CL. Complement therapeutics; history and current progress. Mol Immunol. 2003;40:159–70.PubMedCrossRef
Metadata
Title
Complement and autoimmunity
Authors
Eleonora Ballanti
Carlo Perricone
Elisabetta Greco
Marta Ballanti
Gioia Di Muzio
Maria Sole Chimenti
Roberto Perricone
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Immunologic Research / Issue 2-3/2013
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-013-8422-y

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