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Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 1/2014

01-08-2014

Novel Mechanisms of Action of the Biologicals in Rheumatic Diseases

Authors: Cecilia Beatrice Chighizola, Ennio Giulio Favalli, Pier Luigi Meroni

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2014

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Abstract

Biological drugs targeting pro-inflammatory or co-stimulatory molecules or depleting lymphocyte subsets made a revolution in rheumatoid arthritis (RA) treatment. Their comparable efficacy in clinical trials raised the point of the heterogeneity of RA pathogenesis, suggesting that we are dealing with a syndrome rather than with a single disease. Several tumor necrosis factor-alpha (TNF-α) blockers are available, and a burning question is whether they are biosimilar or not. The evidence of diverse biological effects in vitro is in line with the fact that a lack of efficacy to one TNF-α agent does not imply a non-response to another one. As proteins, biologicals are potentially immunogenic. It has been recently raised that anti-drug antibodies (ADA) may affect their bioavailability and eventually the clinical efficacy through local formation of immune complexes and directly by preventing the interaction between the drug and TNF-α. Regular monitoring of drug and ADA levels appears the best way to tailor anti-TNF-α therapies. Owing to the pleiotropic characteristics of the target, anti-TNF-α blockers may affect several mechanisms beyond rheumatoid synovitis. As TNF-α plays a pivotal role in the induction of early atherosclerosis, treatment with TNF-inhibitors may modulate cholesterol handling, in particular, cholesterol efflux from macrophages. Side effects are a major issue because of the systemic TNF-α blocking action. The efficacy of an anti-C5 monoclonal antibody fused to a peptide targeting inflamed synovia in experimental arthritis opened the way for new strategies: Homing to the synovium of molecules neutralizing TNF would allow to maximize the therapeutic action avoiding the side effects.
Literature
1.
2.
Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R et al (2006) The PREMIER study—a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. A&R 54:26–37
3.
Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D et al (2008) Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 372:375–382PubMed
4.
St. Clair EW, van der heijde MFM, Smolen JS, Main RN, Bathon JM et al (2004) Combination of infliximab and methotrexate therapy for early rheumatoid arthritis. A&R 50:3432–3443
5.
Emery P, Fleischmann RM, Moreland LW, Hsia HC, Strusberg I, Durez P et al (2009) Golimumab, a human anti–tumor necrosis factor a monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis. A&R 60:2272–2283
6.
Westhovens R, Robles M, Ximenes AC, Nayiager S, Wollenhaupt J, Durez P et al (2009) Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis 68:1870–1877PubMedCentralPubMed
7.
Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenvhoven RF, Stohl W et al (2011) Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis 70:39–46PubMed
8.
Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA et al (2003) Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. A&R 48:35–45
9.
Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI et al (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 340:253–259PubMed
10.
Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M et al (1999) Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group Lancet 354:1932–1939
11.
Keystone E, Heijde D, Mason D Jr, Landewé R, Vollenhoven RV, Combe B et al (2008) Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A&R 58:3319–3329
12.
Keystone E, Genovese MC, Klareskog L, Hsia EC, Hall S, Miranda PC et al (2010) Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: 52-week results of the GO-FORWARD study. Ann Rheum Dis 69:1129–1135PubMed
13.
Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E et al (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371:987–997PubMed
14.
Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C et al (2006) Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 144:865–876PubMed
15.
Smolen JS, Kay J, Doyle MK, Landewè R, Matteson EL, Wollenhaupt J et al (2009) Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 374:210–221PubMed
16.
Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A et al (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67:1516–1523PubMedCentralPubMed
17.
Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J et al (2005) Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 353:1114–1123PubMed
18.
Keystone EC, Cohen SB, Emery P, Kremer JM, Dougados M, Loveless JE et al (2012) Multiple courses of rituximab produce sustained clinical and radiographic efficacy and safety in patients with rheumatoid arthritis and an inadequate response to 1 or more tumor necrosis factor inhibitors: 5-year data from the REFLEX Study. J Rheumatol. doi:10.​3899/​jrheum.​120573
19.
Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, et al (2009) Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database Syst Rev:CD007848
20.
Atzeni F, Antivalle M, Pallavicini FB, Caporali R, Bazzani C, Gorla R et al (2009) Predicting response to anti-TNF treatment in rheumatoid arthritis patients. Autoimmun Rev 8:431–437PubMed
21.
Ingegnoli F, Favalli EG, Meroni PL (2011) Does polymorphysm of genes coding for pro-inflammatory mediators predict the clinical response to tnf alpha blocking agents? A review analysis of the literature. Autoimmun Rev 10:460–463PubMed
22.
van Vollenhoven RF (2011) Unresolved issues in biologic therapy for rheumatoid arthritis. Nat Rev Rheumatol 7:205–215PubMed
23.
Perricone C, Ceccarelli F, Valesini G (2011) An overview on the genetic of rheumatoid arthritis: a never-ending story. Autoimmun Rev 10:599–608PubMed
24.
Mcinnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219PubMed
25.
Choy E (2012) Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 51:v3–v11
26.
Schmidt D, Goronzy JJ, Weyand CM (1996) CD4+ CD7− CD28− T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest 97:2027–2037PubMedCentralPubMed
27.
Wegner N, Lundberg K, Kinloch A, Fisher B, Malmström V, Feldmann M et al (2010) Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev 233:34–54PubMed
28.
Wiik AS, van Venrooij WJ, Pruijn GJM (2010) All you wanted to know about anti-CCP but were afraid to ask. Autoimmun Rev 10:90–93PubMed
29.
Szodoray P, Szabó Z, Kapitány A, Gyetvai A, Lakos G, Szántó S et al (2010) Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis. Autoimmun Rev 9:140–143PubMed
30.
Moura RA, Graca L, Fonseca JE (2012) To B or not to B the conductor of rheumatoid arthritis orchestra. Clin Rev Allergy Immunol 43:281–291PubMed
31.
Benucci M, Manfredi M, Puttini PS, Atzeni F (2010) Predictive factors of response to rituximab therapy in rheumatoid arthritis: what do we know today? Autoimmun Rev 9:801–803PubMed
32.
Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361:888–898PubMed
33.
34.
Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Mazurov V et al (2012) Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis DOI: annrheumdis-2012-201601
35.
Mcinnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442PubMed
36.
Cohen SB, Cohen SB, Dore RK, Dore RK, Lane NE, Lane NE et al (2008) Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 58:1299–1309PubMed
37.
Genovese MC, Cohen S, Moreland LW, Lium D, Robbins S, Newmark R et al (2004) Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 50:1412–1419PubMed
38.
Weinblatt ME, Combe B, Covucci A, Aranda R, Becker J-C, Keystone EC (2006) Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, placebo-controlled study. Arthritis Rheum 54:2807–2816PubMed
39.
Tincani A, Andreoli L, Bazzani C, Bosiso D, Sozzani S (2007) Inflammatory molecules: a target for treatment of systemic autoimmune diseases. Autoimmun Rev 7:1–7PubMed
40.
Atzeni F, Sarzi-Puttini P, Gorla R, Marchesoni A, Caporali R (2011) Switching rheumatoid arthritis treatments: an update. Autoimmun Rev 10:397–403PubMed
41.
42.
Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T (2006) Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum 54:3782–3789PubMed
43.
Favalli EG, Marchesoni A, Colombo GL, Sinigaglia L (2008) Pattern of use, economic burden and vial optimization of infliximab for rheumatoid arthritis in Italy. Clin Exp Rheumatol 26:45–51PubMed
44.
45.
Bendtzen K (2011) Is there a need for immunopharmacologic guidance of anti-tumor necrosis factor therapies? Arthritis Rheum 63:867–870PubMed
46.
Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A et al (2003) Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 348:601–608PubMed
47.
Radstake TRDJ, Svenson M, Eijsbouts AM, Van Den Hoogen FHJ, Enevold C, van Riel PLCM et al (2009) Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis 68:1739–1745PubMed
48.
Emi Aikawa N, Carvalho JF, Artur Almeida Silva C, Bonfá E (2009) Immunogenicity of anti-TNF-α agents in autoimmune diseases. Clin Rev Allergy Immunol 38:82–89
49.
Bendtzen K, Ainsworth M, Steenholdt C, Thomsen OØ, Brynskov J (2009) Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand J Gastroenterol 44:774–781PubMed
50.
Dubey S, Kerrigan N, Mills K, Scott DG (2009) Bronchospasm associated with anti-TNF treatment. Clin Rheumatol 28:989–992PubMed
51.
Descotes J, Gouraud A (2008) Clinical immunotoxicity of therapeutic proteins. Expert Opin Drug Metab Toxicol 4:1537–1549PubMed
52.
Bendtzen K, Svenson M (2011) Enzyme immunoassays and radioimmunoassays for quantification of anti-TNF biopharmaceuticals and anti-drug antibodies. In: Tovey MG (ed) Detection and quantification of antibodies to biopharmaceuticals. Practical and applied considerations. John Wiley & Sons, Inc, West Sussex, pp 83–101
53.
Bendtzen K (2008) Immunogenicity of anti-TNF antibodies. In: van de Weert M, Møller EH (eds) Immunogenicity of biopharmaceuticals, vol VIII. Springer, New York, pp 189–203
54.
Svenson M, Geborek P, Saxne T, Bendtzen K (2007) Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies. Rheumatology (Oxford) 46:1828–1834
55.
Lallemand C, Kavrochorianou N, Steenholdt C, Bendtzen K, Ainsworth MA, Meritet J-F et al (2011) Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists. J Immunol Methods 373:229–239PubMed
56.
Rigby WFC (2007) Drug Insight: different mechanisms of action of tumor necrosis factor antagonists—passive–aggressive behavior? Nat Rev Clin Pract 4:227–233
57.
Mitoma H, Horiuchi T, Tsukamoto H, Tamimoto Y, Kimoto Y, Uchino A et al (2008) Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor alpha-expressing cells: comparison among infliximab, etanercept, and adalimumab. Arthritis Rheum 58:1248–1257PubMed
58.
Nesbitt A, Fossati G, Bergin M, Stephens P, Stephens S, Foulkes R et al (2007) Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm Bowel Dis 13:1323–1332PubMed
59.
Lügering A, Schmidt M, Lügering N, Pauels HG, Domschke W, Kucharzik T (2001) Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology 121:1145–1157PubMed
60.
Kirchner S, Holler E, Haffner S, Andreesen R, Eissner G (2004) Effect of different tumor necrosis factor (TNF) reactive agents on reverse signaling of membrane integrated TNF in monocytes. Cytokine 28:67–74PubMed
61.
Harashima S, Horiuchi T, Hatta N, Morita C, Higuchi M, Sawabe T et al (2001) Outside-to-inside signal through the membrane TNF-alpha induces E-selectin (CD62E) expression on activated human CD4+ T cells. J Immunol 166:130–136PubMed
62.
Vudattu NK, Holler E, Ewing P, Schulz U, Haffner S, Burger V et al (2005) Reverse signalling of membrane-integrated tumour necrosis factor differentially regulates alloresponses of CD4+ and CD8+ T cells against human microvascular endothelial cells. Immunology 115:536–543PubMedCentralPubMed
63.
van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I et al (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 124:1774–1785PubMed
64.
Yu M, Shi W, Zhang J, Niu L, Chen Q, Yan D et al (2009) Influence of reverse signaling via membrane TNF-alpha on cytotoxicity of NK92 cells. Eur J Cell Biol 88:181–191PubMed
65.
Nurmohamed MT (2009) Cardiovascular risk in rheumatoid arthritis. Autoimmun Rev 8:663–667PubMed
66.
Sarzi-Puttini P, Atzeni F, Gerli R, Bartoloni E, Doria A, Barskova T et al (2010) Cardiac involvement in systemic rheumatic diseases: an update. Autoimmun Rev 9:849–852PubMed
67.
Watson DJ, Rhodes T, Guess HA (2003) All-cause mortality and vascular events among patients with rheumatoid arthritis, osteoarthritis, or no arthritis in the UK General Practice Research Database. J Rheumatol 30:1196–1202PubMed
68.
Bartoloni E, Alunno A, Bistoni O, Gerli R (2011) Cardiovascular risk in rheumatoid arthritis and systemic autoimmune rheumatic disorders: a suggested model of preventive strategy. Clin Rev Allergy Immunol. doi:10.​1007/​s12016-010-8251
69.
Bergholm R, Leirisalo-Repo M, Vehkavaara S, Makimattila S, Taskinen MR, Yki-Jarvinen H (2002) Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Arterioscler Thromb Vasc Biol 22:1637–1641PubMed
70.
Hannawi S, Marwick TH, Thomas R (2009) Inflammation predicts accelerated brachial arterial wall changes in patients with recent onset rheumatoid arthritis. Arthritis Res Ther 11:R5.1
71.
van Sijl AM, Peters MJ, Dk K, de Vet HC, Gonzalez-Gay MA, Smulders YM et al (2011) Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum 40:389–397PubMed
72.
Bartoloni E, Alunno A, Bistoni O, Gerli R (2010) How early is the atherosclerotic risk in rheumatoid arthritis? Autoimmun Rev 9:701–707PubMed
73.
Brady S, de Courten B, Reid CM, Cicuttini FM, de Courten MP, Liew D (2009) The role of traditional cardiovascular risk factors among patients with rheumatoid arthritis. J Rheumatol 36:34–40PubMed
74.
Bartoloni E, Shoenfeld Y, Gerli R (2011) Inflammatory and autoimmune mechanisms in the induction of atherosclerotic damage in systemic rheumatic diseases: two faces of the same coin. Arthritis Care Res 63:178–183
75.
Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catalano A et al (2010) From endothelial dysfunction to atherosclerosis. Autoimmun Rev 9:830–834PubMed
76.
Gerli R, Bartoloni Bocci EB, Sherer Y, Vaudo G, Moscatelli S, Shoenfeld Y (2008) Association of anti-cyclic citrullinated peptide antibodies with subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum Dis 67:724–725PubMed
77.
Peters MJ, van Halm VP, Voskuyl AE, Smulders YM, Boers M, Lems WF et al (2009) Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study. Arthritis Rheum 61:1571–1579PubMed
78.
Situnayake R, Sitas G (1997) Dyslipidemia and rheumatoid arthritis. Ann Rheum Dis 56:41–42
79.
Lazarevic MB, Vitic J, Mladenovic V, Myones BL, Skosey JL, Swedler WI (1992) Dyslipoproteinemia in the course of active rheumatoid arthritis. Semin Arthritis Rheum 22:172–178PubMed
80.
Vaisar T, Pennathur S, Green PS, Gharib SA, Hoofnagle AN, Cheung MC et al (2007) Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J Clin Invest 117:746–756PubMedCentralPubMed
81.
McMahon M, Grossman J, FitzGerald J, Dahlin-Lee E, Wallace DJ, Thong BY et al (2006) Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 54:2541–2549PubMed
82.
Cederholm A, Svenungsson E, Stengel D, Fei GZ, Pockeley AG, Ninio E et al (2004) Platelet-activating factor-acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus. Arthritis Rheum 50:2869–2876PubMed
83.
Dinu A, Merrill JT, Shen C, Antonov IV, Myones BL, Lahita RG (1998) Frequency of antibodies to the cholesterol transport apolipoprotein A1 in patients with SLE. Lupus 7:355–360PubMed
84.
Vaarala O, Alfthan G, Jauhiainen M, Leirisalo-Repo M, Aho K, Palosuo T (1993) Cross-reaction between antibodies to oxidised low-density lipoprotein and to cardiolipin in systemic lupus erythematosus. Lancet 341:923–925PubMed
85.
Ohashi R, Mu H, Wang X, Yao Q, Chen C (2005) Reverse cholesterol transport and cholesterol efflux in atherosclerosis. Q J Med 98:845–856
86.
Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K et al (2011) Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med 364:127–135PubMedCentralPubMed
87.
Azzam KM, Fessler MB (2012) Crosstalk between reverse cholesterol transport and innate immunity. Trends Endocrinol Metab 23:169–178PubMedCentralPubMed
88.
Atzeni F, Turiel M, Caporali R, Cavagna L, Tomasoni L, Sitia et al (2010) The effects of pharmacological therapy on the cardiovascular system of patients with systemic rheumatic diseases. Autoimmun Rev 9:835–839PubMed
89.
Chighizola C, Schioppo T, Ingegnoli F, Meroni PL (2012) Potential effect of anti-inflammatory treatment on reducing the cardiovascular risk in rheumatoid arthritis. Curr Vasc Pharmacol 43:292–301
90.
Fon Tacer K, Kuzman D, Seliskar M, Pompon D, Rozman D (2007) TNF-α interferes with lipid homeostasis and activates acute and proatherogenic process. Physiol Genomics 31:216–227PubMed
91.
Zhang Y, McGillicuddy FC, Hinkle CC, O'Neill S, Glick JM, Rothblat GH et al (2010) Adipocyte modulation of high-density lipoprotein cholesterol. Circulation 121:1347–1355PubMedCentralPubMed
92.
Macor P, Durigutto P, De Maso L, Garrovo C, Biffi S, Cortini A et al (2012) Treatment of arthritis models by targeting synovial endothelium with a neutralizing recombinant antibody to C5. Arthritis Rheum 64:2559–2567PubMed
93.
Brodeurm JP, Ruddy S, Schwartz LB, Moxley G (1991) Synovial fluid levels of complement SCb-9 and fragment Bb are elevated in patients with rheumatoid arthritis. Arthritis Rheum 34:1531–1537
94.
Chen M, Daha MR, Kallenberg GC (2010) The complement system in systemic autoimmune diseases. J Autoimmun 34:276–286
95.
Hietala MA, Nandakumar KS, Persson L, Fahlen S, Holmdahl R, Pekna M (2004) Complement activation by both classical and alternative pathway is critical for the effector phase of arthritis. J Immunol 34:1208–1216
96.
Wang Y, Kristan J, Hao L, Lenkoski CS, Shen Y, Matis LA (2000) A role for complement in antibody-mediated inflammation: C5-deficient DBA/1 mice are resistant to collagen-induced arthritis. J Immunol 164:4340–4347PubMed
97.
Ji H, Ohmura K, Mahmood U, Lee DM, Hofhuis FM, Boackle SA et al (2002) Arthritis critically dependent on innate immune system players. Immunity 16:157–168PubMed
98.
Banda NK, Takahashi M, Levitt B, Glogowska M, Nicholas J, Takahashi K et al (2010) Essential role of complement mannose-binding lectin-associated serine-protyeases-1/3 in the murine collagen antibody-induced model of inflammatory arthritis. J Immunol 185:5598–5606PubMedCentralPubMed
99.
100.
Whaley K, Guc D, Gulati P, Lappin D (1992) Synthesis of complement components by synovial membrane. Immunopharmacology 24:83–89PubMed
101.
Ballanti E, Perricone E, di Muzio G, Kroegler B, Chimenti MS, Graceffa D et al (2011) Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationship with anti-TNF inhibitors. Autoimmun Rev 10:617–623PubMed
102.
Robbins DL, Fiegal DW Jr, Leek JC, Shapiro R, Wiesner K (1986) Complement activation by 19S IgM rheumatoid factor: relationship to disease activity in rheumatoid arthritis. J Rheumatol 13:33–38PubMed
103.
Sato Y, Sato R, Watanabe H, Kogure A, Watanabe K, Nishimaki T et al (1993) Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors. Ann Rheum Dis 52:795–800PubMedCentralPubMed
104.
Sato Y, Watanabe H, Kogure A, Miyata M, Watanabe K, Nishimaki T et al (1995) Complement-activating properties of IgM rheumatoid factors reacting with IgG subclasses. Clin Rheumatol 14:425–428PubMed
105.
Trouw LA, Haisma EM, Levarht EW, van der Woude D, Ioan-Facsinay A, Daha M et al (2009) Anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathways. Arthritis Rheum 60:1923–1931PubMed
106.
Wolbink GJ, Brouwer MC, Buysman S, ten Berge IJM, Hack CE (1996) CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes. J Immunol 157:473–479PubMed
107.
Sjöberg A, Onnerfjord P, Mörgelin M, Heinegård D, Blom AM (2005) The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q. J Biol Chem 280:32301–32308PubMed
108.
Groeneveld TW, Oroszlan M, Owens RT, Faber-Krol MC, Bakker AC, Arlaud GJ et al (2005) Interactions of the extracellular matrix proteoglycans decorin and biglycan with C1q and collectins. J Immunol 175:4715–4723PubMed
109.
Happonen KE, Heinegård D, Saxne T, Blom AM (2012) Interactions of the complement system with molecules of extracellular matrix: relevance for joint diseases. Immunobiology 217:1088–1096PubMed
110.
Kurreeman FA, Goulielmos GN, Alizadeh BZ, Rueda B, Houwing-Duistermaat J, Sanchez E et al (2009) The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases. Ann Rheum Dis 69:696–699PubMed
111.
Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B et al (2007) TRAF1-C5 as a risk locus for rheumatoid arthritis—a genomewide study. N Engl J Med 357:1199–1209PubMedCentralPubMed
112.
Wang Y, Rollins SA, Madri JA, Matis LA (1995) Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease. Proc Natl Acad Sci U S A 92:8955–8959PubMedCentralPubMed
113.
Woodruff TM, Strachan AJ, Dryburgh N, Shiels IA, Reid RC, Fairlie DP et al (2002) Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis Rheum 46:2476–2485PubMed
114.
Kaplan M (2002) Eculizumab (alexion). Curr Opin Investig Drugs 3:1017–1023PubMed
115.
Rosenblum H, Amital H (2011) Anti-TNF therapy: safety aspects of taking the risk. Autoimmun Rev 10:563–568PubMed
116.
Polachek A, Caspi D, Elkayam O (2012) The perioperative use of biologic agents in patients with rheumatoid arthritis. Autoimmun Rev DOI:j.autrev.2012.04.001
117.
Henry A, Gong HP, Nesbitt A (2011) Mapping the certolizumab pegol epitope on TNF and comparison with infliximab, adalimumab and etanercept. Ann Rheum Dis 70(Suppl3):249
Metadata
Title
Novel Mechanisms of Action of the Biologicals in Rheumatic Diseases
Authors
Cecilia Beatrice Chighizola
Ennio Giulio Favalli
Pier Luigi Meroni
Publication date
01-08-2014
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 1/2014
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-013-8359-x

Other articles of this Issue 1/2014

Clinical Reviews in Allergy & Immunology 1/2014 Go to the issue

ReviewPaper

Recommendations for the Management of Beta-Lactam Intolerance

ReviewPaper

Semaphorins: Their Dual Role in Regulating Immune-Mediated Diseases

Erratum

Erratum to: Infectious Aspects and the Etiopathogenesis of Rheumatoid Arthritis

ReviewPaper

Unique Topics and Issues in Rheumatology and Clinical Immunology

OriginalPaper

Hypersensitivity Reactions to Corticosteroids

ReviewPaper

The Clinical Significance of Posttranslational Modification of Autoantigens
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

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Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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