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Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 3/2015

01-12-2015

Vasculitides and the Complement System: a Comprehensive Review

Authors: Maria Sole Chimenti, Eleonora Ballanti, Paola Triggianese, Roberto Perricone

Published in: Clinical Reviews in Allergy & Immunology | Issue 3/2015

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Abstract

Systemic vasculitides are a group of rare diseases characterized by inflammation of the arterial or venous vessel wall, causing stenosis or thrombosis. Clinical symptoms may be limited to skin or to other organs or may include multiple manifestations as systemic conditions. The pathogenesis is related to the presence of leukocytes in the vessels and to the IC deposition, which implies the activation of the complement system (CS) and then the swelling and damage of vessel mural structures. The complement system (CS) is involved in the pathogenesis of several autoimmune diseases, including systemic vasculitides. This enzymatic system is a part of the innate immune system, and its function is linked to the modulation of the adaptive immunity and in bridging innate and adaptive responses. Its activation is also critical for the development of natural antibodies and T cell response and for the regulation of autoreactive B cells. Complement triggering contributes to inflammation-driven tissue injury, which occurs during the ischemia/reperfusion processes, vasculitides, nephritis, arthritis, and many others diseases. In systemic vasculitides, a group of uncommon diseases characterized by blood vessel inflammation, the contribution of CS in the development of inflammatory damage has been demonstrated. Treatment is mainly based on clinical manifestations and severity of organ involvement. Evidences on the efficacy of traditional immunosuppressive therapies have been collected as well as data from clinical trials that involve the modulation of the CS. In particular in small-medium-vessel vasculitides, the CS represents an attractive target. Herein, we reviewed the pathogenetic role of CS in these systemic vasculitides as urticarial vasculitis, ANCA-associated vasculitides, anti-glomerular basement membrane disease, cryoglobulinaemic vasculitides, Henoch-Schönlein purpura/IgA nephropathy, and Kawasaki disease and therefore its potential therapeutic use in this context.
Literature
1.
Reinhold-Keller E, Herlyn K, Wagner-Bastmeyer R, Gross WL (2005) Stable incidence of primary systemic vasculitides over five years: results from the German vasculitis register. Arthritis Rheum 53:93–99CrossRefPubMed
2.
Waller R, Ahmed A, Patel I, Luqmani R (2013) Update on the classification of vasculitis. Best Pract Res Clin Rheumatol 27:3–17CrossRefPubMed
3.
Fauci AS, Haynes BF, Katz P (1978) The spectrum of vasculitis: clinical, pathological, immunologic, and therapeutic considerations. Ann Intern Med 89:660–676CrossRefPubMed
4.
Lie JT (1994) Nomenclature and classification of vasculitis: plus ça change, plus c’est la même chose. Arthritis Rheum 37:181–186CrossRefPubMed
5.
Jennette JC (2013) Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol 17:603–606PubMedCentralCrossRefPubMed
6.
Brogan PA (2007) What’s new in the aetiopathogenesis of vasculitis? Pediatr Nephrol 22:1083–1094CrossRefPubMed
7.
8.
Mukhtyar C, Guillevin L, Cid MC et al (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 68:310–317CrossRefPubMed
9.
Mizuno M, Morgan BP (2004) The possibilities and pitfalls for anti-complement therapies in inflammatory diseases. Curr Drug Targets Inflamm Allergy 3:87–96CrossRefPubMed
10.
Ballanti E, Perricone C, Greco E, Ballanti MD, Muzio G, Chimenti MS, Perricone R (2013) Complement and autoimmunity. Immunol Res 56:477–491CrossRefPubMed
11.
Lay WH, Nussenzweig V (1968) Receptors for transducing complex of human B elimination of self-reactive B cells up on complement on leukocytes. J Exp Med 128:991–1009PubMedCentralCrossRefPubMed
12.
Carroll MC (2000) The role of complement in B cell activation and tolerance. Adv Immunol 74:61–88CrossRefPubMed
13.
14.
Chen M, Daha MR, Kallenberg CG (2010) The complement system in systemic autoimmune disease. J Autoimmun 34:276–286CrossRef
15.
Grotz W, Baba HA, Becker JU, Baumgärtel MW (2009) Hypocomplementemic urticarial vasculitis syndrome: an interdisciplinary challenge. Dtsch Arztebl Int 106:756–763PubMedCentralPubMed
16.
17.
18.
Lienesch DW, Sherman KE, Metzger A, Shen GQ (2006) Anti-Clq antibodies in patients with chronic hepatitis C infection. Clin Exp Rheumatol 24:183–185PubMed
19.
Jara LJ, Navarro C, Medina G, Vera-Lastra O, Saavedra MA (2009) Hypocomplementemic urticarial vasculitis syndrome. Curr Rheumatol Rep 11:410–415CrossRefPubMed
20.
Brouwer E, Tervaert JW, Horst G, van der Huitema MG, Giessen M, Limburg PC, Kallenberg CG (1991) Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener’s granulomatosis and clinically related disorders. Clin Exp Immunol 83:379–386PubMedCentralCrossRefPubMed
21.
Stone JH, Talor M, Stebbing J et al (2000) Test characteristics of immunofluorescence and ELISA tests in 856 consecutive patients with possible ANCA-associated conditions. Arthritis Care Res 13:424–434CrossRefPubMed
22.
Danila MI, Bridges SL Jr (2008) Update on pathogenic mechanisms of systemic necrotizing vasculitis. Curr Rheumatol Rep 10:430–435CrossRefPubMed
23.
van der Tervaert JW, Woude FJ, Fauci AS et al (1989) Association between active Wegener’s granulomatosis and anticytoplasmic antibodies. Arch Intern Med 149:2461–2465CrossRefPubMed
24.
Franchi L, Eigenbrod T, Nunez G (2009) Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol 183:792–796PubMedCentralCrossRefPubMed
25.
Mariathasan S, Weiss DS, Newton K et al (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–232CrossRefPubMed
26.
27.
Lamprecht P, Csernok E, Gross WL (2006) Effector memory T cells as driving force of granuloma formation and autoimmunity in Wegener’s granulomatosis. J Intern Med 260:187–191CrossRefPubMed
28.
Wilde B, Thewissen M, van Damoiseaux J, Paassen P, Witzke O, Tervaert JW (2010) T cells in ANCA-associated vasculitis: what can we learn from lesional versus circulating T cells? Arthritis ResTher 12:204CrossRef
29.
30.
Schreiber A, Xiao H, Jennette JC, Schneider W, Luft FC, Kettritz R (2009) C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J Am Soc Nephrol 20:289–298PubMedCentralCrossRefPubMed
31.
Xiao H, Schreiber A, Heeringa P, Falk RJ, Jennette JC (2007) Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol 170:52–64PubMedCentralCrossRefPubMed
32.
De Groot K, Rasmussen N, Bacon PA et al (2005) Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 52:2461–2469CrossRefPubMed
33.
Pagnoux C, Mahr A, Hamidou MA et al (2008) Azathioprine of methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 359:2790–2803CrossRefPubMed
34.
Ballanti ED, Muzio G, Novelli L, Perricone C, Perricone R (2012) Churg-Strauss syndrome with neurologic manifestations: successful treatment with intravenous immunoglobulins. Isr Med Assoc J 14:583–585PubMed
35.
Svetlicky N, Blank M, Zandman-Goddard G (2012) The beneficial effects of intravenous immunoglobulin for antineutrophil cytoplasmic antibody-positive vasculitis. Isr Med Assoc J 14:568–569PubMed
36.
Polachek A, Caspi D, Elkayam O (2013) Granulomatosis and polyangiitis: the rituximab option. Isr Med Assoc J 15:193–194PubMed
37.
Casian, A. (2011), Plasma exchange for severe renal vasculitis: long-term follow-up of the MEPEX trial. Clin. Exp. Immunol. 164 (Suppl. 1):52
38.
Kluth DC, Rees AJ (1999) Anti-glomerular basement membrane disease. J Am Soc Nephrol 10:2446–2453PubMed
39.
Segelmark M, Hellmark T, Wieslander J (2003) The prognostic significance in Goodpasture’s disease of specificity, titre and affinity of anti-glomerular- basement-membrane antibodies. Nephron Clin Pract 94:59–68CrossRef
40.
Lerner RA, Glassock RJ, Dixon FJ (1999) The role of anti-glomerular basement membrane antibody in the pathogenesis of human glomerulonephritis. J Am Soc Nephrol 10:1389–1404PubMed
41.
Ohlsson S, Herlitz H, Lundberg S, Selga D, Mölne J, Wieslander J, Segelmark M (2014) Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease. Am J Kidney Dis 63:289–293CrossRefPubMed
42.
Fischer EG, Lager DJ (2006) Anti-glomerular basement membrane glomerulonephritis: a morphologic study of 80 cases. Am J Clin Pathol 125:445–450CrossRefPubMed
43.
Sheerin NS, Springall T, Carroll MC, Hartley B, Sacks SH (1997) Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice. Clin Exp Immunol 110:403–409PubMedCentralCrossRefPubMed
44.
Otten MA, Groeneveld TW, Flierman R et al (2009) Both complement and IgG fc receptors are required for development of attenuated antiglomerular basement membrane nephritis in mice. J Immunol 183:3980–3988CrossRefPubMed
45.
Hu SY, Jia XY, Yang XW, Yu F, Cui Z, Zhao MH (2013) Glomerular C1q deposition and serum anti-C1q antibodies in anti-glomerular basement membrane disease. BMC Immunol 21:14–42
46.
Hisano S, Matsushita M, Fujita T, Takeshita M, Iwasaki H (2007) Activation of the lectin complement pathway in post-streptococcal acute glomerulonephritis. Pathol Int 57:351–357CrossRefPubMed
47.
Roos A, Rastaldi MP, Calvaresi N et al (2006) Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol 17:1724–1734CrossRefPubMed
48.
49.
Ma R, Cui Z, Liao YH, Zhao MH (2013) Complement activation contributes to the injury and outcome of kidney in human anti-glomerular basement membrane disease. J Clin Immunol 33:172–178CrossRefPubMed
50.
Syeda UA, Singer NG, Magrey M (2013) Anti-glomerular basement membrane antibody disease treated with rituximab: a case based review. Semin Arthritis Rheum 42:567–572CrossRefPubMed
51.
Peto P, Salama AD (2011) Update on anti-glomerular basement membrane disease. Curr Opin Rheumatol 23:32–37CrossRefPubMed
52.
Dammacco F, Battaglia S, Gesualdo L, Racanelli V (2013) Goodpasture’s disease: a report of ten cases and a review of the literature. Autoimmun Rev 12:1101–1108CrossRefPubMed
53.
Brouet JC, Clouvel JP, Danon F, Klein M, Seligmann M (1974) Biologic and clinical significance of cryoglobulins. Am J Med 57:775–788CrossRefPubMed
54.
Sansonno D, Tucci FA, Ghebrehiwet B et al (2009) Role of the receptor for the globular domain of C1q protein in the pathogenesis of hepatitis C virus-related cryoglobulin vascular damage. J Immunol 183:6013–6020PubMedCentralCrossRefPubMed
55.
Cacoub P, Saadoun D (2008) Hepatitis C virus infection induced vasculitis. Clin Rev Allergy Immunol 35:30–39CrossRefPubMed
56.
57.
Vitali C, Ferri C, Nasti P, La Civita L, Mazzantini M, Longombardo G, Bombardieri S (1994) Hypercomplementaemia as a marker of the evolution from benign to malignant B-cell proliferation in patients with type II mixed cryoglobulinaemia. Br J Rheumatol 33:791–792CrossRefPubMed
58.
Tarantino A, Anelli A, Costantino AD, Vecchi A, Monti G, Massaro L (1978) Serum complement pattern in essential mixed cryoglobulinaemia. Clin Exp Immunol 32:77–85PubMedCentralPubMed
59.
Sansonno DD, Re V, Lauletta G, Tucci FA, Boiocchi M, Dammacco F (2003) Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood 101:3818–3826CrossRefPubMed
60.
Saadoun DR, Rigon M, Sene D et al (2010) Rituximab plus Peg-interferon-alpha/ribavirin compared with Peg-interferon-alpha/ribavirin in hepatitis C-related mixed cryoglobulinemia sequential therapy with antiviral agents. Blood 116:326–334CrossRefPubMed
61.
Ozen S, Pistorio A, Iusan SM et al (2010) EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 69:798–806CrossRefPubMed
62.
Davin JC (2011) Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy. Clin J Am Soc Nephrol 6:679–689CrossRefPubMed
63.
Newburger JW, Takahashi M, Gerber MA et al (2004) Diagnosis, treatment, and long-term management of Kawasaki disease. Circulation 110:2747–2771CrossRefPubMed
64.
65.
Hartopo AB, Setianto BY (2013) Coronary artery sequel of Kawasaki disease in adulthood, a concern for internists and cardiologists. Acta Med Indones 45:69–75PubMed
66.
Belizna CC, Hamidou MA, Levesque H, Guillevin L, Shoenfeld Y (2008) Infection and vasculitis. Rheumatology (Oxford) 48:475–482CrossRef
67.
Kaneda Y (1983) Complement system in immunological disease of infants and children: the role of the complement system in Kawasaki disease. Japanese Journal of Allergology 32:376–385PubMed
68.
Kohsaka T, Abe J, Asahina T, Kobayashi N (1994) Classical pathway complement activation in Kawasaki syndrome. J Allergy Clin Immunol 93:520–525CrossRefPubMed
69.
Biezeveld MH, Geissler J, Weverling GJ, Kuipers IM, Lam J, Ottenkamp J, Kuijpers TW (2006) Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease. Arthritis Rheum 54:369–376CrossRefPubMed
70.
Nakamura A, Okigaki M, Miura N, Suzuki C, Ohno N, Kametani F, Hamaoka K (2014) Involvement of mannose-binding lectin in the pathogenesis of Kawasaki disease-like murine vasculitis. Clin Immunol 153:64–72CrossRefPubMed
71.
72.
Daniels LB, Gordon JB, Burns JC (2012) Kawasaki disease: late cardiovascular sequelae. Curr Opin Cardiol 27:572–577CrossRefPubMed
73.
Kobayashi T, Saji T, Otani T et al (2012) Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE-study): a randomized, open-label, blinded-endpoints trial. Lancet 379:1613–1620CrossRefPubMed
74.
Cicardi M, Zanichelli A (2010) Replacement therapy with C1 esterase inhibitors for hereditary angioedema. Drugs Today 46:867–874CrossRefPubMed
75.
Duehrkop C, Banz Y, Spirig R et al (2013) C1 esterase inhibitor reduces lower extremity ischemia/reperfusion injury and associated lung damage. Plos ONE 8:e72059PubMedCentralCrossRefPubMed
76.
77.
Risitano AM (2012) Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological disorders. Immunobiology 217:1080–1087CrossRefPubMed
78.
Riedl M, Orth-Höller D, Würzner R (2014) An update on the thrombotic microangiopathies hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Semin Thromb Hemost 40:413–415CrossRefPubMed
79.
Vivarelli M, Emma F (2014) Treatment of c3 glomerulopathy with complement blockers. Semin Thromb Hemost 40:472–477CrossRefPubMed
80.
Radhakrishnan S, Lunn A, Kirschfink M et al (2012) Eculizumab and refractory membranoproliferative glomerulonephritis. N Engl J Med 366:1165–1166CrossRefPubMed
81.
Rosenblad, T. Rebetz, J. Johansson, M. Békássy, Z. Sartz, L. Karpman, D. (2014), Eculizumab treatment for rescue of renal function in IgA nephropathy. Pediatr. Nephrol. Jun 13
82.
Dairaghi, D. Leleti, M. Miao, S. et al. Clinical dose selection of the C5a receptor antagonist CCX168 for the phase 2 ANCA-associated renal vasculitis clinical trial (the CLEAR trial), 49th European Renal Association–European Dialysis and Transplant Association (ERA–EDTA) Congress, 2012, (Paris, France).
83.
Hartung HP, Mouthon L, Ahmed R, Jordan S, Laupland KB, Jolles S (2009) Clinical applications of intravenous immunoglobulins (IVIg)—beyond immunodeficiencies and neurology. Clin Exp Immunol 158(Suppl 1):23–33PubMedCentralCrossRefPubMed
84.
Ballow M (2011) The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol 127:315–323CrossRefPubMed
85.
Smith, R.M. Jones, R.B. Jayne, D.R. (2012), Progress in treatment of ANCA-associated vasculitis. Arthritis Res. Ther.14, 210.
86.
Jayne DR, Chapel H, Adu D, Misbah S, O’Donoghue D, Scott D, Lockwood CM (2000) Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 93:433–439CrossRefPubMed
87.
Martinez V, Cohen P, Pagnoux C et al (2008) French Vasculitis Study Group. Intravenous immunoglobulins for relapses of systemic vasculitides associated with antineutrophil cytoplasmic autoantibodies: results of a multicenter, prospective, open-label study of twenty-two patients. Arthritis Rheum 58:308–317CrossRefPubMed
88.
Morgan BP, Harris CL (2003) Complement therapeutics; history and current progress. Mol Immunol 40:159–170CrossRefPubMed
Metadata
Title
Vasculitides and the Complement System: a Comprehensive Review
Authors
Maria Sole Chimenti
Eleonora Ballanti
Paola Triggianese
Roberto Perricone
Publication date
01-12-2015
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 3/2015
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-014-8453-8

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