Novel mechanisms of action of the biologicals in rheumatic diseases

Clinical Reviews in Allergy and Immunology

Volumn 47, Issue 1, 2014, Pages 6-16

  Chighizola, Cecilia Beatrice ^a,b,c   Favalli, Ennio Giulio ^a   Meroni, Pier Luigi ^a,b,c  

^a ISTITUTO ORTOPEDICO GAETANO PINI   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

^c ISTITUTO AUXOLOGICO ITALIANO   (Italy)

Author keywords

Biological agents; Biosimilarity; Immunogenicity; Rheumatoid arthritis

Indexed keywords

ABATACEPT; ADALIMUMAB; ARGININE DEIMINASE; BIOLOGICAL PRODUCT; C REACTIVE PROTEIN; CARTILAGE OLIGOMERIC MATRIX PROTEIN; CD20 ANTIBODY; CERTOLIZUMAB PEGOL; CHOLESTEROL; COMPLEMENT COMPONENT C5A; COMPLEMENT MEMBRANE ATTACK COMPLEX; CYTOKINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DRUG ANTIBODY; ETANERCEPT; FC RECEPTOR; GOLIMUMAB; HIGH DENSITY LIPOPROTEIN; INFLIXIMAB; LOW DENSITY LIPOPROTEIN; OSTEOCLAST DIFFERENTIATION FACTOR; OXIDIZED LOW DENSITY LIPOPROTEIN; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RITUXIMAB; SCAVENGER RECEPTOR BI; TOCILIZUMAB; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; TUMOR NECROSIS FACTOR INHIBITOR; ANTIBODIES, MONOCLONAL; ANTIGEN-ANTIBODY COMPLEX; ANTIRHEUMATIC AGENTS; BIOLOGICAL PRODUCTS; COMPLEMENT C5; TUMOR NECROSIS FACTOR-ALPHA;

ANTIGEN ANTIBODY COMPLEX; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; ARTERIAL WALL THICKNESS; ATHEROSCLEROSIS; BIOLOGICAL ACTIVITY; BIOLOGICAL THERAPY; CYTOKINE PRODUCTION; DISEASE COURSE; DISEASE SEVERITY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG MECHANISM; ENZYME LINKED IMMUNOSORBENT ASSAY; EXPERIMENTAL ARTHRITIS; HUMAN; HUMORAL IMMUNITY; IMMUNOGENICITY; INFLAMMATION; LEUKOCYTE; LIPOPROTEIN BLOOD LEVEL; MACROPHAGE; MONOCYTE; NATURAL KILLER CELL; NONHUMAN; PATHOGENESIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RHEUMATIC DISEASE; RHEUMATOID ARTHRITIS; SYNOVITIS; T LYMPHOCYTE ACTIVATION; TARGET CELL; TARGET ORGAN; ANIMALS; ANTAGONISTS AND INHIBITORS; ANTIGEN-ANTIBODY COMPLEX; BIOLOGICAL AVAILABILITY; DRUG EFFECTS; HUMANS; IMMUNOLOGY; LYMPHOCYTE DEPLETION; METABOLISM; METHODS; MOLECULAR TARGETED THERAPY; RHEUMATIC DISEASES; SYNOVIAL MEMBRANE;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGEN-ANTIBODY COMPLEX; ANTIRHEUMATIC AGENTS; BIOLOGICAL AVAILABILITY; BIOLOGICAL PRODUCTS; BIOLOGICAL THERAPY; CHOLESTEROL; COMPLEMENT C5; HUMANS; LYMPHOCYTE DEPLETION; MOLECULAR TARGETED THERAPY; RHEUMATIC DISEASES; SYNOVIAL MEMBRANE; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84906215442     PISSN: 10800549     EISSN: 15590267     Source Type: Journal    
DOI: 10.1007/s12016-013-8359-x     Document Type: Review

References (117)

1. Atzeni F, Benucci M, Sallì S, Dongiovanni S, Boccassini L, Sarzi-Puttini P (2012) Different effects of biological drugs in rheumatoid arthritis. Autoimmun Rev. doi:10.1016/j.autrev.2012.10.020
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 372:375-382
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 68:1870-1877
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 70:39-46
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 340:253-259 (Pubitemid 29063266)
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 69:1129-1135
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 371:987-997 (Pubitemid 351392039)
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 144:865-876 (Pubitemid 46768126)
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 374:210-221
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 67:1516-1523
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 353:1114-1123 (Pubitemid 41317434)
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 8:431-437
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 10:460-463
22. van Vollenhoven RF (2011) Unresolved issues in biologic therapy for rheumatoid arthritis. Nat Rev Rheumatol 7:205-215
23. Perricone C, Ceccarelli F, Valesini G (2011) An overview on the genetic of rheumatoid arthritis: a never-ending story. Autoimmun Rev 10:599-608
24. Mcinnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205-2219
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 97:2027-2037 (Pubitemid 26143956)
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 233:34-54
28. Wiik AS, van Venrooij WJ, Pruijn GJM (2010) All you wanted to know about anti-CCP but were afraid to ask. Autoimmun Rev 10:90-93
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 9:140-143
30. Moura RA, Graca L, Fonseca JE (2012) To B or not to B the conductor of rheumatoid arthritis orchestra. Clin Rev Allergy Immunol 43:281-291
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 9:801-803
32. Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361:888-898
33. Mijnheer G, Prakken BJ, van Wijk F (2013) The effect of autoimmune arthritis treatment strategies on regulatory T-cell dynamics. Curr Opin Rheumatol 25. doi:10.1097/BOR.0b013e32835d0ee4
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 7:429-442
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, placebocontrolled, phase II clinical trial. Arthritis Rheum 58:1299-1309 (Pubitemid 351705919)
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 50:1412-1419 (Pubitemid 38608062)
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 54:2807-2816 (Pubitemid 44497759)
39. Tincani A, Andreoli L, Bazzani C, Bosiso D, Sozzani S (2007) Inflammatory molecules: a target for treatment of systemic auto-immune diseases. Autoimmun Rev 7:1-7 (Pubitemid 47633384)
40. Atzeni F, Sarzi-Puttini P, Gorla R, Marchesoni A, Caporali R (2011) Switching rheumatoid arthritis treatments: an update. Autoimmun Rev 10:397-403
41. Atzeni F, Talotta R, Benucci M, Salaffi F, Cassinotti A, Varisco V et al (2012) Immunogenicity and autoimmunity during anti-TNF therapy. Autoimmun Rev. doi:10.1016/j.autrev.2012.10.021
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 54:3782-3789 (Pubitemid 44955878)
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 26:45-51 (Pubitemid 351395047)
44. Olivieri I, D'Angelo S, Padula A, Leccese P, Nigro A, Palazzi C (2012) Can we reduce the dosage of biologics in spondyloarthritis? Autoimmun Rev. doi:10.1016/j.autrev.2012.08.013
45. Bendtzen K (2011) Is there a need for immunopharmacologic guidance of anti-tumor necrosis factor therapies? Arthritis Rheum 63:867-870
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 348:601-608 (Pubitemid 36204954)
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 68:1739-1745
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 44:774-781
50. Dubey S, Kerrigan N, Mills K, Scott DG (2009) Bronchospasm associated with anti-TNF treatment. Clin Rheumatol 28:989-992
51. Descotes J, Gouraud A (2008) Clinical immunotoxicity of therapeutic proteins. Expert Opin Drug Metab Toxicol 4:1537-1549
52. Bendtzen K, Svenson M (2011) Enzyme immunoassays and radio-immunoassays 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 (Pubitemid 350168300)
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 373:229-239
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 58:1248-1257 (Pubitemid 351705913)
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 13:1323-1332 (Pubitemid 350206841)
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 121:1145-1157 (Pubitemid 33022095)
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 28:67-74 (Pubitemid 39295687)
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 166:130-136 (Pubitemid 32038425)
62. Vudattu NK, Holler E, Ewing P, Schulz U, Haffner S, Burger Vet 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 115:536-543 (Pubitemid 41032441)
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 124:1774-1785 (Pubitemid 36666774)
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 88:181-191
65. Nurmohamed MT (2009) Cardiovascular risk in rheumatoid arthritis. Autoimmun Rev 8:663-667
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 9:849-852
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 30:1196-1202 (Pubitemid 36666340)
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 22:1637-1641
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 40:389-397
72. Bartoloni E, Alunno A, Bistoni O, Gerli R (2010) How early is the atherosclerotic risk in rheumatoid arthritis? Autoimmun Rev 9:701-707
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 36:34-40
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 9:830-834
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 67:724-725 (Pubitemid 351571944)
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 61:1571-1579
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 22:172-178
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 117:746-756 (Pubitemid 46348533)
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 54:2541-2549 (Pubitemid 44205015)
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 50:2869-2876 (Pubitemid 39209524)
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 7:355-360 (Pubitemid 28347016)
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 341:923-925 (Pubitemid 23109111)
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 (Pubitemid 43071450)
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 364:127-135
87. Azzam KM, Fessler MB (2012) Crosstalk between reverse cholesterol transport and innate immunity. Trends Endocrinol Metab 23:169-178
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 9:835-839
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 31:216-227 (Pubitemid 350014399)
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 121:1347-1355
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 64:2559-2567
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 (Pubitemid 39256000)
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 164:4340-4347 (Pubitemid 30215097)
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 16:157-168 (Pubitemid 34211957)
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 185:5598-5606
99. Mihai S, Nimmerjahn F (2012) The role of Fc receptors and complement in autoimmunity. Autoimmun Rev. doi:10.1016/j.autrev.2012.10.008
100. Whaley K, Guc D, Gulati P, Lappin D (1992) Synthesis of complement components by synovial membrane. Immunopharmacology 24:83-89
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 10:617-623
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 13:33-38 (Pubitemid 16118719)
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 52:795-800 (Pubitemid 23328691)
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 14:425-428
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 60:1923-1931
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 157:473-479 (Pubitemid 26190582)
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 280:32301-32308 (Pubitemid 41361839)
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 175:4715-4723 (Pubitemid 41362013)
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 217:1088-1096
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 69:696-699
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 357:1199-1209 (Pubitemid 47443179)
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 92:8955-8959
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 46:2476-2485
114. Kaplan M (2002) Eculizumab (alexion). Curr Opin Investig Drugs 3:1017-1023
115. Rosenblum H, Amital H (2011) Anti-TNF therapy: safety aspects of taking the risk. Autoimmun Rev 10:563-568
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