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Rheumatology International

Erschienen in:

01.04.2016 | Review Article - Pathology Review

Focal bone involvement in inflammatory arthritis: the role of IL17

verfasst von: Maurizio Rossini, Ombretta Viapiana, Silvano Adami, Luca Idolazzi, Elena Fracassi, Davide Gatti

Erschienen in: Rheumatology International | Ausgabe 4/2016

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Abstract

Conditions such as rheumatoid arthritis (RA) and spondyloarthritis (SpA, such as psoriatic arthritis, PsA, and ankylosing spondylitis, AS) are characterized by an imbalance between osteoclast (OC) bone resorption and osteoblast (OB) bone formation. The two conditions present substantial differences in bone involvement, which is probably related to the different expression of IL17 and TNFα, two cytokines that strongly promote osteoclastogenesis and focal bone erosions. TNFα is the major inflammatory cytokine in RA. It acts by both triggering OC bone erosion via the RANK–RANKL system, and suppressing OB bone formation through the overexpression of DKK1, a powerful inhibitor of the WNT bone anabolic signaling pathway. Differing from TNFα, IL17 promotes also osteogenesis, particularly at inflamed sites undergoing mechanical stress, such as entheses. Therefore, in RA, where overexpression of TNFα is higher than IL17, OC bone resorption largely prevails upon bone formation. In PsA and AS, the prevailing inflammatory cytokine is IL17, which promotes also osteogenesis. Given the prevalent involvement of entheses poor of OC, excess bone formation may even prevail over excess bone resorption. The results of clinical trials support the different pathophysiology of bone involvement in chronic arthritis. Inflammation control through anti-TNFα agents has not resulted in incomparable effects on radiographic progression and excess bone formation in both AS and PsA. Clinical trials investigating IL17 inhibitors, such as secukinumab, in patients with psoriatic disease are underway. The preliminary results on inflammation and symptoms appear positive, while long-term studies are required to demonstrate an effect on excess bone formation.

Adami S, Kanis JA (1995) Assessment of involutional bone loss: methodological and conceptual problems. J Bone Miner Res 10:511–517. doi:10.1002/jbmr.5650100402 PubMedCrossRef

Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261. doi:10.1056/NEJMra053077 PubMedCrossRef

Martin TJ, Seeman E (2008) Bone remodelling: its local regulation and the emergence of bone fragility. Best Pract Res Clin Endocrinol Metab 22:701–722. doi:10.1016/j.beem.2008.07.006 PubMedCrossRef

Kassem M, Marie PJ (2011) Senescence-associated intrinsic mechanisms of osteoblast dysfunctions. Aging Cell 10:191–197. doi:10.1111/j.1474-9726.2011.00669.x PubMedCrossRef

Marie PJ, Kassem M (2011) Extrinsic mechanisms involved in age related defective bone formation. J Clin Endocrinol Metab 96:600–609. doi:10.1210/jc.2010-2113 PubMedCrossRef

Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342. doi:10.1038/nature01658 PubMedCrossRef

Takahashi N, Akatsu T, Udagawa N, Sasaki T, Yamaguchi A, Moseley JM, Martin TJ, Suda T (1988) Osteoblastic cells are involved in osteoclast formation. Endocrinology 123:2600–2602. doi:10.1210/endo-123-5-2600 PubMedCrossRef

Yasuda H, Shima N, Nakagawa N et al (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337. doi:10.1210/endo.139.3.5837 PubMed

Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176. doi:10.1016/S0092-8674(00)81569-X PubMedCrossRef

10.

Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS 3rd, Frankel WN, Lee SY, Choi Y (1997) TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chem 272:25190–25194. doi:10.1074/jbc.272.40.25190 PubMedCrossRef

11.

Baron R, Rawadi G (2007) Minireview: targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 148:2635–2643. doi:10.1210/en.2007-0270 PubMedCrossRef

12.

Canalis E, Giustina A, Bilezikian JP (2007) Mechanisms of anabolic therapies for osteoporosis. N Engl J Med 357:905–906. doi:10.1056/NEJMra067395 PubMedCrossRef

13.

Spencer GJ, Utting JC, Etheridge SL, Arnett TR, Genever PG (2006) Wnt signaling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci 119:1283–1296. doi:10.1242/jcs.02883 PubMedCrossRef

14.

Glass DA 2nd, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G (2005) Canonical WNT signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764. doi:10.1016/j.devcel.2005.02.017 PubMedCrossRef

15.

Rossini M, Gatti D, Adami S (2013) Involvement of WNT/β-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int 93:121–132. doi:10.1007/s00223-013-9749-z PubMedCrossRef

16.

Li J, Sarosi I, Cattley RC et al (2006) Dkk1- mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 39:754–766. doi:10.1016/j.bone.2006.03.017 PubMedCrossRef

17.

Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494. doi:10.1056/NEJMoa030847 PubMedCrossRef

18.

Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden DT (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846. doi:10.1038/nature02040 PubMedCrossRef

19.

Miyamoto K, Yoshida S, Kawasumi M et al (2011) Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. J Exp Med 208:2175–2181. doi:10.1084/jem.20101890 PubMedPubMedCentralCrossRef

20.

Finzel S, Rech J, Schmidt S, Engelke K, Englbrecht M, Schett G (2013) Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arthritis: a micro CT study. Ann Rheum Dis 72:396–400. doi:10.1136/annrheumdis-2011-201075 PubMedCrossRef

21.

Finzel S, Rech J, Schmidt S, Engelke K, Englbrecht M, Stach C, Schett G (2011) Repair of bone erosions in rheumatoid arthritis treated with tumour necrosis factor inhibitors is based on bone apposition at the base of the erosion. Ann Rheum Dis 70:1587–1593. doi:10.1136/ard.2010.148395 PubMedCrossRef

22.

Bromley M, Woolley DE (1984) Chondroclasts and osteoclasts at subchondral sites of erosion in the rheumatoid joint. Arthritis Rheum 27:968–975. doi:10.1002/art.1780270902 PubMedCrossRef

23.

Gravallese EM, Harada Y, Wang JT, Gorn AH, Thornhill TS, Goldring SR (1998) Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am J Pathol 152:943–951PubMedPubMedCentral

24.

Kong YY, Feige U, Sarosi I et al (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304–309. doi:10.1038/46303 PubMedCrossRef

25.

Pettit AR, Ji H, von Stechow D, Müller R, Goldring SR, Choi Y, Benoist C, Gravallese EM (2001) TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol 159:1689–1699. doi:10.1016/S0002-9440(10)63016-7 PubMedPubMedCentralCrossRef

26.

Herman S, Mueller R, Kroenke G, Zerina J, Redlich K, Hueber AJ, Gelse H, Neumann E, Müller-Ladner U, Schett G (2008) Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis. Arthritis Rheum 58:3041–3050. doi:10.1002/art.23943 PubMedCrossRef

27.

Jarrett SJ, Conaghan PG, Sloan VS, Papanastasiou P, Ortmann CE, O’Connor PJ, Grainger AJ, Emery P (2006) Preliminary evidence for a structural benefit of the new bisphosphonate zoledronic acid in early rheumatoid arthritis. Arthritis Rheum 54(5):1410–1414. doi:10.1002/art.21824 PubMedCrossRef

28.

McQueen F, Lloyd R, Doyle A, Robinson E, Lobo M, Exeter M, Taylor WJ, Jones P, Reid IR, Dalbeth N (2011) Zoledronic acid does not reduce MRI erosive progression in PsA but may suppress bone oedema: the Zoledronic Acid in Psoriatic Arthritis (ZAPA) Study. Ann Rheum Dis 70:1091–1094. doi:10.1136/ard.2010.142539 PubMedCrossRef

29.

Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R (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 58:1299–1309. doi:10.1002/art.23417 PubMedCrossRef

30.

Deodhar A, Dore RK, Mandel D, Schechtman J, Shergy W, Trapp R, Ory PA, Peterfy CG, Fuerst T, Wang H, Zhou L, Tsuji W, Newmark R (2010) Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res (Hoboken) 62:569–574. doi:10.1002/acr.20004 CrossRef

31.

U.S. Food and Drug Administration (2013) Drug approvals and databases. Denosumab. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm356667.htm?source=govdelivery. Accessed 11 Oct 2014

32.

Nakashima T, Takayanagi H (2009) Osteoimmunology: crosstalk between the immune and bone systems. J Clin Immunol 29:555–567. doi:10.1007/s10875-009-9316-6 PubMedCrossRef

33.

Takayanagi H (2012) New developments in osteoimmunology. Nat Rev Rheumatol 8:684–689. doi:10.1038/nrrheum.2012.167 PubMedCrossRef

34.

Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT (1999) Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun 265:144–150. doi:10.1006/bbrc.1999.1623 PubMedCrossRef

35.

Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111:821–831. doi:10.1172/JCI200316069 PubMedPubMedCentralCrossRef

36.

Chiu YG, Shao T, Feng C, Mensah KA, Thullen M, Schwarz EM, Ritchlin CT (2010) CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis. Arthritis Res Ther 12:R14. doi:10.1186/ar2915 PubMedPubMedCentralCrossRef

37.

Mirosavljevic D, Quinn JM, Elliott J, Horwood NJ, Martin TJ, Gillespie MT (2003) T-cells mediate an inhibitory effect of interleukin-4 on osteoclastogenesis. J Bone Miner Res 18(6):984–993. doi:10.1359/jbmr.2003.18.6.984 PubMedCrossRef

38.

Li P, Schwarz EM, O’Keefe RJ, Ma L, Boyce BF, Xing L (2004) RANK signaling is not required for TNFα-mediated increase in CD11 OC precursors but is essential for mature OC formation in TNFα-mediated inflammatory arthritis. J Bone Miner Res 19:207–213. doi:10.1359/JBMR.0301233 PubMedCrossRef

39.

Chabaud M, Garnero P, Dayer JM, Guerne PA, Fossiez F, Miossec P (2000) Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis. Cytokine 12:1092–1099. doi:10.1006/cyto.2000.0681 PubMedCrossRef

40.

Agarwal S, Misra R, Aggarwal A (2008) Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases. J Rheumatol 35:515–519PubMed

41.

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4⁺ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132. doi:10.1038/ni1254 PubMedCrossRef

42.

Miossec P, Kolls JK (2012) Targeting IL17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776. doi:10.1038/nrd3794 PubMedCrossRef

43.

Yosef N, Shalek AK, Gaublomme JT et al (2013) Dynamic regulatory network controlling TH17 cell differentiation. Nature 496:461–468. doi:10.1038/nature11981 PubMedPubMedCentralCrossRef

44.

Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6:1133–1141. doi:10.1038/ni1261 PubMedPubMedCentralCrossRef

45.

Hu Y, Shen F, Crellin NK, Ouyang W (2011) The IL17 pathway as a major therapeutic target in autoimmune diseases. Ann NY Acad Sci 1217:60–76. doi:10.1111/j.1749-6632.2010.05825.x PubMedCrossRef

46.

Sato W, Aranami T, Yamamura T (2007) Cutting edge: human Th17 cells are identified as bearing CCR2⁺CCR5⁻ phenotype. J Immunol 178:7525–7529. doi:10.4049/jimmunol.178.12.7525 PubMedCrossRef

47.

Chan AC, Carter PJ (2012) Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 10:301–316. doi:10.1038/nri2761 CrossRef

48.

Yeo L, Toellner KM, Salmon M, Filer A, Buckley CD, Raza K, Scheel-Toellner D (2011) Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis 70:2022–2028. doi:10.1136/ard.2011.153312 PubMedPubMedCentralCrossRef

49.

Boumans MJ, Thurlings RM, Yeo L, Scheel-Toellner D, Vos K, Gerlag DM, Tak PP (2012) Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis. Ann Rheum Dis 71(1):108–113. doi:10.1136/annrheumdis-2011-200198 PubMedCrossRef

50.

Yeo L, Lom H, Juarez M, Snow M, Buckley CD, Filer A, Raza K, Scheel-Toellner D (2015) Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis. Ann Rheum Dis 74(5):928–935. doi:10.1136/annrheumdis-2013-204116 PubMedPubMedCentralCrossRef

51.

Onal M, Xiong J, Chen X, Thostenson JD, Almeida M, Manolagas SC, O’Brien CA (2012) RANKL expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem 287:29851–29860. doi:10.1074/jbc.M112.377945 PubMedPubMedCentralCrossRef

52.

Harre U, Georgess D, Bang H et al (2012) Induction of Osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 122:1791–1802. doi:10.1172/JCI60975 PubMedPubMedCentralCrossRef

53.

Chabaud M, Fossiez F, Taupin JL, Miossec P (1998) Enhancing effect of IL17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol 161:409–414PubMed

54.

Rouvier E, Luciani MF, Mattéi MG, Denizot F, Golstein P (1993) CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol 150:5445–5556PubMed

55.

Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, Miossec P (1999) Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42:963–970. doi:10.1002/1529-0131(199905)42:5<963:AID-ANR15>3.0.CO;2-E PubMedCrossRef

56.

Chabaud M, Miossec P (2001) The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum 44:1293–1303. doi:10.1002/1529-0131(200106)44:6<1293:AID-ART221>3.0.CO;2-T PubMedCrossRef

57.

Lubberts E, Joosten LA, Oppers B, van den Bersselaar L, Coenen-de Roo CJ, Kolls JK, Schwarzenberger P, van de Loo FA, van den Berg WB (2001) IL-1-independent role of IL17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol 167:1004–1013. doi:10.4049/jimmunol.167.2.1004 PubMedCrossRef

58.

Adami S, Cavani A, Rossi F, Girolomoni G (2014) The role of interleukin-17A in psoriatic disease. BioDrugs 28:487–497. doi:10.1007/s40259-014-0098-x PubMedCrossRef

59.

Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H, Maslinski W (2000) High levels of IL17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL17 production via cyclosporine A-sensitive mechanism. J Immunol 164:2832–2838. doi:10.4049/jimmunol.164.5.2832 PubMedCrossRef

60.

Katz Y, Nadiv O, Beer Y (2001) Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukin 1, 6 and 8 in skin and synovial fibroblasts: a possible role as a “fine-tuning cytokine” in inflammation process. Arthritis Rheum 44:2176–2184. doi:10.1002/1529-0131(200109)44:9<2176:AID-ART371>3.0.CO;2-4 PubMedCrossRef

61.

Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP (1998) IL17 stimulates the production and expression of proinflammatory cytokines, IL-1beta and TNF alpha, by human macrophages. J Immunol 160:3513–3521PubMed

62.

Ruddy MJ, Wong GC, Liu XK, Yamamoto H, Kasayama S, Kirkwood KL, Gaffen SL (2004) Functional cooperation between interleukin-17 and tumor necrosis factor-α is mediated by CCAAT/enhancer binding protein family members. J Biol Chem 279:2559–2567. doi:10.1074/jbc.M308809200 PubMedCrossRef

63.

Notley CA, Inglis JJ, Alzabin S, McCann FE, McNamee KE, Williams RO (2008) Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells. J Exp Med 205(11):2491–2497. doi:10.1084/jem.20072707 PubMedPubMedCentralCrossRef

64.

Hull DN, Williams RO, Pathan E, Alzabin S, Abraham S, Taylor PC (2015) Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis. Clin Exp Immunol. doi:10.1111/cei.12626 PubMed

65.

Kikly K, Liu L, Na S, Sedgwick JD (2006) The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 18:670–675. doi:10.1016/j.coi.2006.09.008 PubMedCrossRef

66.

Raychaudhuri SP (2013) Role of IL17 in psoriasis and psoriatic arthritis. Clin Rev Allerg Immunol 44:183–1893. doi:10.1007/s12016-012-8307-1 CrossRef

67.

Gaffen SL (2008) An overview of IL17 function and signalling. Cytokine 43:402–407. doi:10.1016/j.cyto.2008.07.017 PubMedPubMedCentralCrossRef

68.

McInnes IB, Sieper J, Braun J, Emery P, van der Heijde D, Isaacs JD, Dahmen G, Wollenhaupt J, Schulze-Koops H, Kogan J, Ma S, Schumacher MM, Bertolino AP, Hueber W, Tak PP (2014) Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis 73:349–356. doi:10.1136/annrheumdis-2012-202646 PubMedCrossRef

69.

McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewé R, Conaghan PG, Gottlieb AB, Richards H, Pricop L, Ligozio G, Patekar M, Mpofu S, FUTURE 2 Study Group (2015) Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. doi:10.1016/S0140-6736(15)61134-5 PubMedCentral

70.

Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Aelion JA, Lee SH, Codding CE, Kellner H, Ikawa T, Hugot S, Ligozio G, Mpofu S (2014) One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis:phase II, dose-finding, double-blind, randomized, placebo-controlled study. J Rheumatol 41:414–421. doi:10.3899/jrheum.130637 PubMedCrossRef

71.

Evans DM, Spencer CC, Pointon JJ et al (2011) Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet 43:761–767. doi:10.1038/ng.873 PubMedPubMedCentralCrossRef

72.

Cortes A, Hadler J, Pointon JP et al (2013) Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 45:730–738. doi:10.1038/ng.2667 PubMedPubMedCentralCrossRef

73.

Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, Gorman DM, Bowman EP, McClanahan TK, Yearley JH, Eberl G, Buckley CD, Kastelein RA, Pierce RH, Laface DM, Cua DJ (2012) IL-23 induces spondyloarthropathy by acting on ROR-γt+CD3+CD4-CD8- entheseal resident T cells. Nat Med 18:1069–1076. doi:10.1038/nm.2817 PubMedCrossRef

74.

Ruutu M, Thomas G, Steck R, Degli-Esposti MA, Zinkernagel MS, Alexander K, Velasco J, Strutton G, Tran A, Benham H, Rehaume L, Wilson RJ, Kikly K, Davies J, Pettit AR, Brown MA, McGuckin MA, Thomas R (2012) β-glucan triggers spondylarthritis and Crohn’s disease-like ileitis in SKG mice. Arthritis Rheum 64:2211–2222. doi:10.1002/art.34423 PubMedCrossRef

75.

Appel H, Maier R, Wu P, Scheer R, Hempfing A, Kayser R, Thiel A, Radbruch A, Loddenkemper C, Sieper J (2011) Analysis of IL17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther 13:R95. doi:10.1186/ar3370 PubMedPubMedCentralCrossRef

76.

Noordenbos T, Yeremenko N, Gofita I, van de Sande M, Tak PP, Caňete JD, Baeten D (2012) Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheum 64:99–109. doi:10.1002/art.33396 PubMedCrossRef

77.

Baeten D, Baraliakos X, Braun J et al (2013) Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 382:1705–1713. doi:10.1016/S0140-6736(13)61134-4 PubMedCrossRef

78.

Layh-Schmitt G, Colbert RA (2008) The interleukin-23/interleukin-17 axis in spondyloarthritis. Curr Opin Rheumatol 20:392–397. doi:10.1097/BOR.0b013e328303204b PubMedPubMedCentralCrossRef

79.

Wendling D, Cedoz JP, Racadot E, Dumoulin G (2007) Serum IL17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine 74:304–305. doi:10.1016/j.jbspin.2006.11.005 PubMedCrossRef

80.

Singh R, Aggarwal A, Misra R (2007) Th1/Th17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy. J Rheumatol 34:2285–2290PubMed

81.

Shen H, Goodall JC, Hill Gaston JS (2010) Frequency and phenotype of T helper 17 cells in peripheral blood and synovial fluid of patients with reactive arthritis. J Rheumatol 37:2096–2099PubMedCrossRef

82.

Zhang L, Li YG, Li YH, Qi L, Liu XG, Yuan CZ, Hu NW, Ma DX, Li ZF, Yang Q, Li W, Li JM (2012) Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS ONE 7:e31000. doi:10.1371/journal.pone.0031000 PubMedPubMedCentralCrossRef

83.

Kenna TJ, Davidson SI, Duan R, Bradbury LA, McFarlane J, Smith M, Weedon H, Street S, Thomas R, Thomas GP, Brown MA (2012) Enrichment of circulating interleukin-17–secreting interleukin-23 receptor–positive γ/δ T cells in patients with active ankylosing spondylitis. Arthritis Rheum 64:1420–1429. doi:10.1002/art.33507 PubMedCrossRef

84.

Zrioual S, Toh ML, Tournadre A, Zhou Y, Cazalis MA, Pachot A, Miossec V, Miossec P (2008) IL17RA and IL17RC receptors are essential for IL17A-induced ELR + CXC chemokine expression in synoviocytes and are overexpressed in rheumatoid blood. J Immunol 180:655–663. doi:10.4049/jimmunol.180.1.655 PubMedCrossRef

85.

Shen F, Gaffen SL (2008) Structure–function relationships in the IL17 receptor: implications for signal transduction and therapy. Cytokine 41:92–104. doi:10.1016/j.cyto.2007.11.013 PubMedPubMedCentralCrossRef

86.

Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H (2006) Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203:2673–2682. doi:10.1084/jem.20061775 PubMedPubMedCentralCrossRef

87.

Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942–949. doi:10.1038/ni1496 PubMedCrossRef

88.

Romas E, Gillespie MT, Martin TJ (2002) Involvement of receptor activator of NFkappaB ligand and tumor necrosis factor-alpha in bone destruction in rheumatoid arthritis. Bone 30:340–346. doi:10.1016/S8756-3282(01)00682-2 PubMedCrossRef

89.

Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T (1999) IL17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103:1345–1352. doi:10.1172/JCI5703 PubMedPubMedCentralCrossRef

90.

Sadik CD, Kim ND, Alekseeva E, Luster AD (2011) IL17RA signaling amplifies antibody-induced arthritis. PLoS ONE 6:e26342. doi:10.1371/journal.pone.0026342 PubMedPubMedCentralCrossRef

91.

Pickens SR, Chamberlain ND, Volin MV, Gonzalez M, Pope RM, Mandelin AM 2nd, Kolls JK, Shahrara S (2011) Anti-CXCL5 therapy ameliorates IL17-induced arthritis by decreasing joint vascularization. Angiogenesis 14:443–455. doi:10.1007/s10456-011-9227-z PubMedPubMedCentralCrossRef

92.

Koenders MI, Marijnissen RJ, Devesa I, Lubberts E, Joosten LA, Roth J, van Lent PL, van de Loo FA, van den Berg WB (2011) Tumor necrosis factor-interleukin-17 interplay induces S100A8, interleukin-1 beta, and matrix metallo proteinases, and drives irreversible cartilage destruction in murine arthritis: rationale for combination treatment during arthritis. Arthritis Rheum 63:2329–2339. doi:10.1002/art.30418 PubMedCrossRef

93.

Lubberts E, Joosten LA, van de Loo FA, Schwarzenberger P, Kolls J, van den Berg WB (2002) Overexpression of IL17 in the knee joint of collagen type II immunized mice promotes collagen arthritis and aggravates joint destruction. Inflamm Res 51:102–104PubMedCrossRef

94.

Balani D, Aeberli D, Hofstetter W, Seitz M (2013) Interleukin-17A stimulates granulocyte-macrophage colony-stimulating factor release by murine osteoblasts in the presence of 1,25-dihydroxyvitamin D(3) and inhibits murine osteoclast development in vitro. Arthritis Rheum 65:436–446. doi:10.1002/art.37762 PubMedCrossRef

95.

Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, van der Heide D, Landewe R, Lacey D, Richards WG, Schett G (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163. doi:10.1038/nm1538 PubMedCrossRef

96.

Huang H, Zhao N, Xu X, Xu Y, Li S, Zhang J, Yang P (2011) Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells. Cell Prolif 44:420–427. doi:10.1111/j.1365-2184.2011.00769.x PubMedCrossRef

97.

Osta B, Lavocat F, Eljaafari A, Miossec P (2014) Effects of interleukin-17A on osteogenic differentiation of isolated human mesenchymal stem cells. Front Immunol 5:425. doi:10.3389/fimmu.2014.00425 PubMedPubMedCentral

98.

Eyerich K, Pennino D, Scarponi C, Foerster S, Nasorri F, Behrendt H, Ring J, Traidl-Hoffmann C, Albanesi C, Cavani A (2009) IL17 in atopic eczema: linking allergenspecific adaptive and microbial-triggered innate immune response. J Allergy Clin Immunol 123:59–66. doi:10.1016/j.jaci.2008.10.031 PubMedCrossRef

99.

Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, Huang W, Zhang P, Zhang J, Shellito JE, Bagby GJ, Nelson S, Charrier K, Peschon JJ, Kolls JK (2001) Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colonystimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194:519–527. doi:10.1084/jem.194.4.519 PubMedPubMedCentralCrossRef

100.

Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31:787–798. doi:10.1016/j.immuni.2009.09.014 PubMedPubMedCentralCrossRef

101.

Parachuru VP, Coates DE, Milne TJ, Hussaini HM, Rich AM, Seymour GJ (2014) Forkhead box P3-positive regulatory T-cells and interleukin 17-positive T-helper 17 cells in chronic inflammatory periodontal disease. J Periodontal Res 49:817–826. doi:10.1111/jre.12169 PubMedCrossRef

102.

Corneth OB, Mus AM, Asmawidjaja PS, Klein Wolterink RG, van Nimwegen M, Brem MD, Hofman Y, Hendriks RW, Lubberts E (2014) Absence of interleukin-17 receptor A signaling prevents autoimmune inflammation of the joint and leads to a Th2-like phenotype in collagen-induced arthritis. Arthritis Rheumatol 66:340–349. doi:10.1002/art.38229 PubMedCrossRef

103.

Pennino D, Eyerich K, Scarponi C, Carbone T, Eyerich S, Nasorri F, Garcovich S, Traidl-Hoffmann C, Albanesi C, Cavani A (2010) IL17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes. J Immunol 184:4880–4888. doi:10.4049/jimmunol.0901767 PubMedCrossRef

104.

Katayama M, Ohmura K, Yukawa N, Terao C, Hashimoto M, Yoshifuji H, Kawabata D, Fujii T, Iwakura Y, Mimori T (2013) Neutrophils are essential as a source of IL17 in the effector phase of arthritis. PLoS ONE 8:e62231. doi:10.1371/journal.pone.0062231 PubMedPubMedCentralCrossRef

105.

Hueber AJ, Asquith DL, Miller AM, Reilly J, Kerr S, Leipe J, Melendez AJ, McInnes IB (2010) Mast cells express IL17A in rheumatoid arthritis synovium. J Immunol 184:3336–3340. doi:10.4049/jimmunol.0903566 PubMedCrossRef

106.

Suurmond J, Dorjée AL, Boon MR, Knol EF, Huizinga TWJ, Toes REM, Schuerwegh AJM (2011) Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther 13:R150. doi:10.1186/ar3466 PubMedPubMedCentralCrossRef

107.

Crisp AJ, Chapman CM, Kirkham SE, Schiller AL, Krane SM (1984) Articular mastocytosis in rheumatoid arthritis. Arthritis Rheum 27:845–851. doi:10.1002/art.1780270802 PubMedCrossRef

108.

Kopicky-Burd JA, Kagey-Sobotka A, Peters SP, Dvorak AM, Lennox DW, Lichtenstein LM, Wigley FM (1988) Characterization of human synovial mast cells. J Rheumatol 15:1326–1333PubMed

109.

Bridges AJ, Malone DG, Jicinsky J, Chen M, Ory P, Engber W, Graziano FM (1991) Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy. Arthritis Rheum 34:1116–1124. doi:10.1002/art.1780340907 PubMedCrossRef

110.

Gotis-Graham I, McNeil HP (1997) Mast cell responses in rheumatoid synovium. Association of the MCTC subset with matrix turnover and clinical progression. Arthritis Rheum 40:479–489. doi:10.1002/art.1780400314 PubMedCrossRef

111.

Ceponis A, Konttinen YT, Takagi M, Xu JW, Sorsa T, Matucci-Cerinic M, Santavirta S, Bankl HC, Valent P (1998) Expression of stem cell factor (SCF) and SCF receptor (c-kit) in synovial membrane in arthritis: correlation with synovial mast cell hyperplasia and inflammation. J Rheumatol 25:2304–2314PubMed

112.

Frewin DB, Cleland LG, Jonsson JR, Robertson PW (1986) Histamine levels in human synovial fluid. J Rheumatol 13:13–14PubMed

113.

Malone DG, Irani AM, Schwartz LB, Barrett KE, Metcalfe DD (1986) Mast cell numbers and histamine levels in synovial fluids from patients with diverse arthritides. Arthritis Rheum 29:956–963. doi:10.1002/art.1780290803 PubMedCrossRef

114.

Buckley MG, Walters C, Wong WM, Cawley MI, Ren S, Schwartz LB, Walls AF (1997) Mast cell activation in arthritis: detection of alpha- and beta-tryptase, histamine and eosinophil cationic protein in synovial fluid. Clin Sci (Lond) 93:363–370. doi:10.1042/cs0930363 CrossRef

115.

Brodeur JP, Ruddy S, Schwartz LB, Moxley G (1991) Synovial fluid levels of complement SC5b-9 and fragment Bb are elevated in patients with rheumatoid arthritis. Arthritis Rheum 34:1531–1537. doi:10.1002/art.1780341209 PubMedCrossRef

116.

Lavery JP, Lisse JR (1994) Preliminary study of the tryptase levels in the synovial fluid of patients with inflammatory arthritis. Ann Allergy 72:425–427PubMed

117.

Guo Y, Wu Q, Ni B, Mou Z, Jiang Q, Cao Y, Dong H, Wu Y (2014) Tryptase is a candidate autoantigen in rheumatoid arthritis. Immunology 142:67–77. doi:10.1111/imm.12197 PubMedPubMedCentralCrossRef

118.

Rossini M, Zanotti R, Bonadonna P, Artuso A, Caruso B, Schena D, Vecchiato D, Bonifacio M, Viapiana O, Gatti D, Senna G, Riccio A, Passalacqua G, Pizzolo G, Adami S (2011) Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49:880–885. doi:10.1016/j.bone.2011.07.004 PubMedCrossRef

119.

Rossini M, Zanotti R, Viapiana O, Tripi G, Orsolini G, Idolazzi L, Bonadonna P, Schena D, Escribano L, Adami S, Gatti D (2014) Bone involvement and osteoporosis in mastocytosis. Immunol Allergy Clin North Am 34:383–396. doi:10.1016/j.iac.2014.01.011 PubMedCrossRef

120.

Bader-Meunier B, Bulai Livideanu C, Larroche C et al (2014) Association of mastocytosis with inflammatory joint diseases: a series of 31 patients. Semin Arthritis Rheum 44:362–365. doi:10.1016/j.semarthrit.2014.05.016 PubMedCrossRef

121.

Happel KI, Zheng M, Young E, Quinton LJ, Lockhart E, Ramsay AJ, Shellito JE, Schurr JR, Bagby GJ, Nelson S, Kolls JK (2003) Cutting edge: roles of Toll-like receptor 4 and IL 23 in IL 17 expression in response to Klebsiella pneumonia infection. J Immunol 170:4432–4436. doi:10.4049/jimmunol.170.9.4432 PubMedPubMedCentralCrossRef

122.

Sutton C, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KHG (2009) Interleukin 1 and IL 23 induce innate IL 17 production from γδ T cells, amplifying TH17 responses and autoimmunity. Immunity 31:331–341. doi:10.1016/j.immuni.2009.08.001 PubMedCrossRef

123.

Rachitskaya AV, Hansen AM, Horai R, Li Z, Villasmil R, Luger D, Nussenblatt RB, Caspi RR (2008) Cutting edge: NKT cells constitutively express IL 23 receptor and RORγt and rapidly produce IL 17 upon receptor ligation in an IL 6 independent fashion. J Immunol 180:5167–5171. doi:10.4049/jimmunol.180.8.5167 PubMedPubMedCentralCrossRef

124.

Pöllinger B, Junt T, Metzler B, Walker UA, Tyndall A, Allard C, Bay S, Keller R, Raulf F, Di Padova F, O’Reilly T, Horwood NJ, Patel DD, Littlewood-Evans A (2011) TH17 cells, not IL 17 + γδ T cells, drive arthritic bone destruction in mice and humans. J Immunol 186:2602–2612. doi:10.4049/jimmunol.1003370 PubMedCrossRef

125.

Rossini M, Adami S, Viapiana O, Tripi G, Zanotti R, Ortolani R, Vella A, Troplini S, Gatti D (2013) Acute phase response after zoledronic acid is associated with long-term effects on white blood cells. Calcif Tissue Int 93:249–252. doi:10.1007/s00223-013-9750-6 PubMedCrossRef

126.

Viapiana O, Gatti D, Idolazzi L, Fracassi E, Adami S, Troplini S, Povino MR, Rossini M (2014) Bisphosphonates vs infliximab in ankylosing spondylitis treatment. Rheumatology (Oxford) 53:90–94. doi:10.1093/rheumatology/ket321 CrossRef

127.

Borrero CG, Mountz JM, Mountz JD (2011) Emerging MRI methods in rheumatoid arthritis. Nat Rev Rheumatol 7:85–95. doi:10.1038/nrrheum.2010.173 PubMedCrossRef

128.

Proulx ST, Kwok E, You Z, Papuga MO, Beck CA, Shealy DJ, Calvi LM, Ritchlin CT, Awad HA, Boyce BF, Xing L, Schwarz EM (2008) Elucidating bone marrow edema and myelopoiesis in murine arthritis using contrast-enhanced magnetic resonance imaging. Arthritis Rheum 58:2019–2029. doi:10.1002/art.23546 PubMedPubMedCentralCrossRef

129.

Lukas C, van der Heijde D, Fatenejad S, Landewé R (2010) Repair of erosions occurs almost exclusively in damaged joints without swelling. Ann Rheum Dis 69:851–855. doi:10.1136/ard.2009.119156 PubMedCrossRef

130.

Møller Døhn U, Boonen A, Hetland ML, Hansen MS, Knudsen LS, Hansen A, Madsen OR, Hasselquist M, Møller JM, Østergaard M (2009) Erosive progression is minimal, but erosion healing rare, in patients with rheumatoid arthritis treated with adalimumab. A 1-year investigator-initiated follow-up study using high-resolution computed tomography as the primary outcome measure. Ann Rheum Dis 68:1585–1590. doi:10.1136/ard.2008.097048 PubMedCrossRef

131.

Matzelle MM, Gallant MA, Condon KW, Walsh NC, Manning CA, Stein GS, Lian JB, Burr DB, Gravallese EM (2012) Resolution of inflammation induces OB function and regulates the Wnt signaling pathway. Arthritis Rheum 64:1540–1550. doi:10.1002/art.33504 PubMedPubMedCentralCrossRef

132.

Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K, Peterfy CG, Hensor E, Wakefield RJ, O’Connor PJ, Emery P (2008) An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum 58:2958–2967. doi:10.1002/art.23945 PubMedCrossRef

133.

Walsh NC, Reinwald S, Manning CA, Condon KW, Iwata K, Burr DB, Gravallese EM (2009) OB function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res 24:1572–1585. doi:10.1359/jbmr.090320 PubMedCrossRef

134.

Luyten FP, Tylzanowski P, Lories RJ (2009) Wnt signaling and osteoarthritis. Bone 44:522–527. doi:10.1016/j.bone.2008.12.006 PubMedCrossRef

135.

Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, Mueller R, Haibel H, Baraliakos X, Hempfing A, Rudwaleit M, Sieper J, Schett G (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60:3257–3562. doi:10.1002/art.24888 PubMedCrossRef

136.

Kwon SR, Lim MJ, Suh CH, Park SG, Hong YS, Yoon BY, Kim HA, Choi HJ, Park W (2012) Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy. Rheumatol Int 32:2523–2527. doi:10.1007/s00296-011-1981-0 PubMedCrossRef

137.

Daoussis D, Liossis SN, Solomou EE, Tsanaktsi A, Bounia K, Karampetsou M, Yiannopoulos G, Andonopoulos AP (2010) Evidence that Dkk 1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 62:150–158. doi:10.1002/art.27231 PubMedCrossRef

138.

Heiland GR, Appel H, Poddubnyy D, Zwerina J, Hueber A, Haibel H, Baraliakos X, Listing J, Rudwaleit M, Schett G, Sieper J (2012) High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 71:572–574. doi:10.1136/annrheumdis-2011-200216 PubMedCrossRef

139.

Rossini M, Viapiana O, Adami S, Fracassi E, Idolazzi L, Dartizio C, Povino MR, Orsolini G, Gatti D (2015) In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathyroid hormone, bone erosions and bone mineral density. Clin Exp Rheumatol 33:77–83PubMed

140.

Lories R (2011) The balance of tissue repair and remodeling in chronic arthritis. Nat Rev Rheumatol 7:700–707. doi:10.1038/nrrheum.2011.156 PubMedCrossRef

141.

Schett G (2014) Bone formation in psoriatic arthritis: a report from the GRAPPA 2013 annual meeting. J Rheumatol 41:1218–1219. doi:10.3899/jrheum.140173 PubMedCrossRef

142.

McGonagle D, Lories RJ, Tan AL, Benjamin M (2007) The concept of a ‘‘synovio-entheseal complex’’ and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 56:2482–2491. doi:10.1002/art.22758 PubMedCrossRef

143.

Maksymowych WP, Chiowchanwisawakit P, Clare T, Pedersen SJ, Østergaard M, Lambert RG (2009) Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: evidence of a relationship between inflammation and new bone formation. Arthritis Rheum 60:93–102. doi:10.1002/art.24132 PubMedCrossRef

144.

Poggenborg RP, Wiell C, Bøyesen P, Boonen A, Bird P, Pedersen SJ, Sørensen IJ, Madsen OR, Slot O, Møller JM, Hasselquist M, Kubassova O, Østergaard M (2014) No overall damage progression despite persistent inflammation in adalimumab-treated psoriatic arthritis patients: results from an investigator-initiated 48-week comparative magnetic resonance imaging, computed tomography and radiography trial. Rheumatology (Oxford) 53:746–756. doi:10.1093/rheumatology/ket426 CrossRef

145.

van der Heijde D, Salonen D, Weissman BN, Landewé R, Maksymowych WP, Kupper H, Ballal S, Gibson E, Wong R (2009) Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 11(4):R127. doi:10.1186/ar2794 PubMedPubMedCentralCrossRef

146.

van der Heijde D, Landewé R, Einstein S, Ory P, Vosse D, Ni L, Lin SL, Tsuji W, Davis JC Jr (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 58(5):1324–1331. doi:10.1002/art.23471 PubMedCrossRef

147.

van der Heijde D, Landewé R, Baraliakos X, Houben H, van Tubergen A, Williamson P, Xu W, Baker D, Goldstein N, Braun J (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 58(10):3063–3070. doi:10.1002/art.23901 PubMedCrossRef

148.

Haroon N, Inman RD, Learch TJ, Weisman MH, Lee M, Rahbar MH, Ward MM, Reveille JD, Gensler LS (2013) The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 65(10):2645–2654. doi:10.1002/art.38070 PubMedPubMedCentral

149.

Haroon N (2014) The effect of tumor necrosis factor-blockade on new bone formation in ankylosing spondylitis: what is the evidence? Curr Opin Rheumatol 26(4):389–394. doi:10.1097/BOR.0000000000000077 PubMedCrossRef

150.

Baraliakos X, Braun J, Sieper J, Baeten DL, Readie A, Ligozio G, Richards H (2015) Secukinumab reduces sacroiliac joint and spinal inflammation in patients with ankylosing spondylitis: MRI data from a phase 3 randomised, double-blind, placebo-controlled study. Ann Rheum Dis 74(2):281

151.

van der Heijde D, Landewé RBM, Mease PJ, McInnes IB, Conaghan PG, Pricop L, Ligozio G, Richards H, Mpofu S (2014) Secukinumab, a monoclonal antibody to interleukin-17A, provides significant and sustained inhibition of joint structural damage in active psoriatic arthritis regardless of prior TNF inhibitors or concomitant methotrexate: a phase 3 randomized, double-blind, placebo-controlled study. Arthritis Rheum 66:S424CrossRef

152.

Tan AL, Tanner SF, Waller ML, Hensor EM, Burns A, Jeavons AP, Bury RF, Emery P, McGonagle D (2013) High-resolution [18F]fluoride positron emission tomography of the distal interphalangeal joint in psoriatic arthritis–a bone-enthesis-nail complex. Rheumatology (Oxford) 52:898–904. doi:10.1093/rheumatology/kes384 CrossRef

153.

Idolazzi L, Vantaggiato E, Salgarello M, Perandini S, Fassio A, Povino MR, Fracassi E, Viapiana O, Gatti D, Rossini M, Adami S (2015) 18F-Fluoride PET/CT for detection of axial involvement in ankylosing spondylitis. Ann Rheum Dis 74(2):1158. doi:10.1136/annrheumdis-2015-eular.3789

Titel: Focal bone involvement in inflammatory arthritis: the role of IL17
verfasst von: Maurizio Rossini
Ombretta Viapiana
Silvano Adami
Luca Idolazzi
Elena Fracassi
Davide Gatti
Publikationsdatum: 01.04.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 4/2016
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-015-3387-x

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Focal bone involvement in inflammatory arthritis: the role of IL17

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