{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:21:41Z","timestamp":1791451301368,"version":"4.3.3"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["CIRG19may0052"],"award-info":[{"award-number":["CIRG19may0052"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["MH 095:003\\016-0001"],"award-info":[{"award-number":["MH 095:003\\016-0001"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["MH 095:003\\016-0002"],"award-info":[{"award-number":["MH 095:003\\016-0002"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NMRC\/CG\/M003\/2017"],"award-info":[{"award-number":["NMRC\/CG\/M003\/2017"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NMRC\/MOHIAFCAT2\/005\/2015"],"award-info":[{"award-number":["NMRC\/MOHIAFCAT2\/005\/2015"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NMRC\/OFLCG\/002\/2018"],"award-info":[{"award-number":["NMRC\/OFLCG\/002\/2018"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NMRC\/TA\/0059\/2017"],"award-info":[{"award-number":["NMRC\/TA\/0059\/2017"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NMRC\/TCR\/0015-NCC\/2016"],"award-info":[{"award-number":["NMRC\/TCR\/0015-NCC\/2016"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Juvenile spondyloarthritis (JSpA) refers to a diverse spectrum of immune-mediated inflammatory arthritides whose onset occurs in late childhood and adolescence. Like its adult counterpart, JSpA is typified by a strong association with human leukocyte antigen-B27 (HLA-B27) and potential axial involvement, while lacking rheumatoid factor (RF) and distinguishing autoantibodies. A characteristic manifestation of JSpA is enthesitis (inflammation of insertion sites of tendons, ligaments, joint capsules or fascia to bone), which is commonly accompanied by bone resorption and new bone formation at affected sites. In this Review, advances in the role of HLA-B27, enthesitis and its associated osteoproliferation in JSpA pathophysiology and treatment options will be discussed. A deeper appreciation of how these elements contribute to the JSpA disease mechanism will better inform diagnosis, prognosis and therapy, which in turn translates to an improved quality of life for patients.<\/jats:p>","DOI":"10.3389\/fmed.2021.666772","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T05:27:11Z","timestamp":1621488431000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Juvenile Spondyloarthritis: What More Do We Know About HLA-B27, Enthesitis, and New Bone Formation?"],"prefix":"10.3389","volume":"8","author":[{"given":"Shi Huan","family":"Tay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Guan","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Yao","family":"Leong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Albani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaschawee","family":"Arkachaisri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1002\/art.22709","article-title":"Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor","volume":"56","author":"Saurenmann","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B2","doi-asserted-by":"publisher","first-page":"472","DOI":"10.3109\/03009741003742722","article-title":"Incidence and prevalence of juvenile idiopathic arthritis in Catalonia (Spain)","volume":"39","author":"Modesto","year":"2010","journal-title":"Scand J Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jbspin.2009.11.002","article-title":"Prevalence and distribution of juvenile idiopathic arthritis in a region of Western France","volume":"77","author":"Solau-Gervais","year":"2010","journal-title":"Joint Bone Spine"},{"key":"B4","first-page":"111","article-title":"The distribution of juvenile idiopathic arthritis in the eastern Mediterranean: results from the registry of the Turkish Paediatric Rheumatology Association","volume":"29","author":"Demirkaya","year":"2011","journal-title":"Clin Exp Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.3899\/jrheum.120642","article-title":"Enthesitis-related arthritis is associated with higher pain intensity and poorer health status in comparison with other categories of juvenile idiopathic arthritis: the Childhood Arthritis and Rheumatology Research Alliance Registry","volume":"39","author":"Weiss","year":"2012","journal-title":"J Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3455","DOI":"10.1007\/s10067-020-05081-9","article-title":"Juvenile idiopathic arthritis in Southeast Asia: the Singapore experience over two decades","volume":"39","author":"Tanya","year":"2020","journal-title":"Clin Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12969-020-00489-8","article-title":"Do geography and ethnicity play a role in juvenile Spondyloarthritis? A multi-center binational retrospective study","volume":"19","author":"Ghantous","year":"2021","journal-title":"Pediatr Rheumatol Online J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1136\/ard.46.4.277","article-title":"Incidence and prevalence of juvenile chronic arthritis: a population survey","volume":"46","author":"Andersson","year":"1987","journal-title":"Ann Rheum Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1136\/ard.55.9.608","article-title":"Incidence of chronic juvenile rheumatic diseases in Finland during 1980-1990","volume":"14","author":"Kaipiainen-Seppanen","year":"1996","journal-title":"Clin Exp Rheumatol"},{"key":"B10","first-page":"1981","article-title":"The incidence of pediatric rheumatic diseases: results from the Canadian Pediatric Rheumatology Association Disease Registry","volume":"23","author":"Malleson","year":"1996","journal-title":"J Rheumatol"},{"key":"B11","first-page":"1975","article-title":"Pediatric rheumatology in the United Kingdom: data from the British Pediatric Rheumatology Group National Diagnostic Register","volume":"23","author":"Symmons","year":"1996","journal-title":"J Rheumatol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12969-018-0238-9","article-title":"Clinical features of children with enthesitis-related juvenile idiopathic arthritis \/ juvenile spondyloarthritis followed in a French tertiary care pediatric rheumatology centre","volume":"16","author":"Goirand","year":"2018","journal-title":"Pediatr Rheumatol Online J"},{"key":"B13","first-page":"2256","article-title":"Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy","volume":"27","author":"Minden","year":"2000","journal-title":"J Rheumatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e000366","DOI":"10.1136\/rmdopen-2016-000366","article-title":"Course of patients with juvenile spondyloarthritis during 4 years of observation, juvenile part of GESPIC","volume":"3","author":"Wei\u00df","year":"2017","journal-title":"RMD Open."},{"key":"B15","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.bone.2015.04.035","article-title":"Bone development","volume":"80","author":"Berendsen","year":"2015","journal-title":"Bone"},{"key":"B16","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1242\/dev.105536","article-title":"A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation","volume":"142","author":"Kozhemyakina","year":"2015","journal-title":"Development"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.bone.2009.03.671","article-title":"Local communication on and within bone controls bone remodeling","volume":"44","author":"Henriksen","year":"2009","journal-title":"Bone"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1002\/art.24888","article-title":"Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis","volume":"60","author":"Appel","year":"2009","journal-title":"Arthritis Rheum"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1097\/SCS.0000000000003625","article-title":"Biology of bone formation, fracture healing, and distraction osteogenesis","volume":"28","author":"Runyan","year":"2017","journal-title":"J Craniofac Surg"},{"key":"B20","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s11914-011-0058-z","article-title":"Osteoporosis: a paradox in ankylosing spondylitis","volume":"9","author":"Carter","year":"2011","journal-title":"Curr Osteoporos Rep"},{"key":"B21","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.rdc.2012.08.003","article-title":"Pathophysiology of new bone formation and ankylosis in spondyloarthritis","volume":"38","author":"Lories","year":"2012","journal-title":"Rheum Dis Clin North Am"},{"key":"B22","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3389\/fimmu.2019.00679","article-title":"Osteoimmunology of bone loss in inflammatory rheumatic diseases","volume":"10","author":"Coury","year":"2019","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"R104","DOI":"10.1186\/ar2496","article-title":"The relationship between inflammation and new bone formation in patients with ankylosing spondylitis","volume":"10","author":"Baraliakos","year":"2008","journal-title":"Arthritis Res Ther"},{"key":"B24","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1002\/art.24132","article-title":"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","volume":"60","author":"Maksymowych","year":"2009","journal-title":"Arthritis Rheum"},{"key":"B25","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/nm1538","article-title":"Dickkopf-1 is a master regulator of joint remodeling","volume":"13","author":"Diarra","year":"2007","journal-title":"Nat Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1136\/ard.2008.102046","article-title":"Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints","volume":"69","author":"Uderhardt","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1002\/art.22372","article-title":"Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis","volume":"56","author":"Lories","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1002\/art.23901","article-title":"Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis","volume":"58","author":"van","year":"2008","journal-title":"Arthritis Rheum"},{"key":"B29","doi-asserted-by":"publisher","first-page":"R127","DOI":"10.1186\/ar2794","article-title":"Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years","volume":"11","author":"van","year":"2009","journal-title":"Arthritis Res Ther"},{"key":"B30","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1136\/annrheumdis-2012-202698","article-title":"Continuous long-term anti-TNF therapy does not lead to an increase in the rate of new bone formation over 8 years in patients with ankylosing spondylitis","volume":"73","author":"Baraliakos","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"B31","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/ar2642","article-title":"Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis","volume":"11","author":"Lories","year":"2009","journal-title":"Arthritis Res Ther"},{"key":"B32","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1046\/j.1469-7580.2001.19950503.x","article-title":"The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites","volume":"199","author":"Benjamin","year":"2001","journal-title":"J Anat."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.1002\/art.23755","article-title":"Distinct topography of erosion and new bone formation in achilles tendon enthesitis: implications for understanding the link between inflammation and bone formation in spondylarthritis","volume":"58","author":"McGonagle","year":"2008","journal-title":"Arthritis Rheum"},{"key":"B34","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1136\/annrheumdis-2013-203643","article-title":"Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells","volume":"73","author":"Jacques","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"B35","doi-asserted-by":"publisher","first-page":"258","DOI":"10.5435\/00124635-200107000-00006","article-title":"Diffuse idiopathic skeletal hyperostosis: musculoskeletal manifestations","volume":"9","author":"Belanger","year":"2001","journal-title":"J Am Acad Orthop Surg"},{"key":"B36","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/art.38291","article-title":"Review: the interleukin-23\/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond","volume":"66","author":"Smith","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/s41584-018-0044-2","article-title":"IL-17 in the immunopathogenesis of spondyloarthritis","volume":"14","author":"Taams","year":"2018","journal-title":"Nat Rev Rheumatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1172\/JCI5703","article-title":"IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis","volume":"103","author":"Kotake","year":"1999","journal-title":"J Clin Invest"},{"key":"B39","doi-asserted-by":"publisher","first-page":"R29","DOI":"10.1186\/ar2936","article-title":"Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors","volume":"12","author":"Adamopoulos","year":"2010","journal-title":"Arthritis Res Ther"},{"key":"B40","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.bone.2016.01.010","article-title":"Proinflammatory T cells and IL-17 stimulate osteoblast differentiation","volume":"84","author":"Croes","year":"2016","journal-title":"Bone"},{"key":"B41","doi-asserted-by":"publisher","first-page":"5950395","DOI":"10.1155\/2017\/5950395","article-title":"Different modulatory effects of IL-17, IL-22, and IL-23 on osteoblast differentiation","volume":"2017","author":"Zhang","year":"2017","journal-title":"Mediat Inflamm"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1136\/annrheumdis-2018-213328","article-title":"Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study","volume":"77","author":"Baeten","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1111\/1756-185X.13552","article-title":"Urinalysis monitoring in children with Henoch-Schonlein purpura: is it time to revise?","volume":"22","author":"Wang","year":"2019","journal-title":"Int J Rheum Dis"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.bbrc.2020.02.054","article-title":"IL-17 promotes osteoblast differentiation, bone regeneration, and remodeling in mice","volume":"524","author":"Kim","year":"2020","journal-title":"Biochem Biophys Res Commun"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4466","DOI":"10.1002\/jcp.29323","article-title":"IL-17 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes","volume":"235","author":"Liao","year":"2020","journal-title":"J Cell Physiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"10928","DOI":"10.1038\/ncomms10928","article-title":"IL-17-producing gammadelta T cells enhance bone regeneration","volume":"7","author":"Ono","year":"2016","journal-title":"Nat Commun"},{"key":"B47","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/art.40736","article-title":"Expansion of interleukin-22- and granulocyte-macrophage colony-stimulating factor-expressing, but not interleukin-17A-expressing, group 3 innate lymphoid cells in the inflamed joints of patients with spondyloarthritis","volume":"71","author":"Blijdorp","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nm.2817","article-title":"IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells","volume":"18","author":"Sherlock","year":"2012","journal-title":"Nat Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1136\/annrheumdis-2017-eular.6421","article-title":"FRI0427 First description of gamma delta t cells at normal human enthesis","volume":"76","author":"Cuthbert","year":"2017","journal-title":"Ann Rheum Dis."},{"key":"B50","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41467-018-07911-6","article-title":"RORgammat inhibition selectively targets IL-17 producing iNKT and gammadelta-T cells enriched in Spondyloarthritis patients","volume":"10","author":"Venken","year":"2019","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1093\/rheumatology\/key128","article-title":"Modified stoke ankylosing spondylitis spinal score as an outcome measure to assess the impact of treatment on structural progression in ankylosing spondylitis","volume":"58","author":"van","year":"2019","journal-title":"Rheumatology"},{"key":"B52","doi-asserted-by":"publisher","first-page":"21094","DOI":"10.1038\/s41598-020-78204-6","article-title":"Anti-IL-17A treatment reduces serum inflammatory, angiogenic and tissue remodeling biomarkers accompanied by less synovial high endothelial venules in peripheral spondyloarthritis","volume":"10","author":"Kaaij","year":"2020","journal-title":"Sci Rep."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1056\/NEJMoa1505066","article-title":"Secukinumab, an interleukin-17a inhibitor, in ankylosing spondylitis","volume":"373","author":"Baeten","year":"2015","journal-title":"N Engl J Med"},{"key":"B54","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/art.40728","article-title":"Three Multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of ustekinumab in axial spondyloarthritis","volume":"71","author":"Deodhar","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.4049\/jimmunol.1300274","article-title":"Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase\/prostaglandin E2 pathway, independent of IL-23","volume":"191","author":"Paulissen","year":"2013","journal-title":"J Immunol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.rdc.2020.01.003","article-title":"Juvenile-versus adult-onset spondyloarthritis: similar, but different","volume":"46","author":"Weiss","year":"2020","journal-title":"Rheum Dis Clin North Am"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1038\/s41467-017-01771-2","article-title":"Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis","volume":"8","author":"Al-Mossawi","year":"2017","journal-title":"Nat Commun"},{"key":"B58","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1136\/annrheumdis-2018-214944","article-title":"Identification of myeloid cells in the human enthesis as the main source of local IL-23 production","volume":"78","author":"Bridgewood","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"B59","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1097\/BOR.0000000000000569","article-title":"The ties that bind: skin, gut and spondyloarthritis","volume":"31","author":"Gracey","year":"2019","journal-title":"Curr Opin Rheumatol"},{"key":"B60","first-page":"128","article-title":"IL-23 receptor gene rs7517847 and rs1004819 SNPs in ulcerative colitis","volume":"9","author":"Hayatbakhsh","year":"2012","journal-title":"Iran J Immunol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1007\/s00011-012-0509-8","article-title":"Association of IL23R polymorphisms with psoriasis and psoriatic arthritis: a meta-analysis","volume":"61","author":"Zhu","year":"2012","journal-title":"Inflamm Res"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1093\/rheumatology\/kez363","article-title":"The effect of tumour necrosis factor inhibitors on radiographic progression in axial spondyloarthritis: a systematic literature review","volume":"58","author":"Boers","year":"2019","journal-title":"Rheumatology"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1759720X20906040","DOI":"10.1177\/1759720X20906040","article-title":"Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: a structured literature review","volume":"12","author":"Baraliakos","year":"2020","journal-title":"Ther Adv Musculoskelet Dis."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e0177231","DOI":"10.1371\/journal.pone.0177231","article-title":"Ankylosing spondylitis patients at risk of poor radiographic outcome show diminishing spinal radiographic progression during long-term treatment with TNF-alpha inhibitors","volume":"12","author":"Maas","year":"2017","journal-title":"PLoS ONE"},{"key":"B65","doi-asserted-by":"publisher","first-page":"i15","DOI":"10.1093\/rheumatology\/keaa040","article-title":"Enthesitis in psoriatic arthritis (Part 2): imaging","volume":"59","author":"Kaeley","year":"2020","journal-title":"Rheumatology."},{"key":"B66","doi-asserted-by":"publisher","first-page":"337","DOI":"10.3389\/fmed.2020.00337","article-title":"High-resolution peripheral quantitative computed tomography for bone evaluation in inflammatory rheumatic disease","volume":"7","author":"Klose-Jensen","year":"2020","journal-title":"Front Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s13075-020-02327-4","article-title":"Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis","volume":"22","author":"Christodoulou-Vafeiadou","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2588","DOI":"10.1002\/eji.1830271018","article-title":"A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55\/p75 TNF receptor signaling","volume":"27","author":"Alexopoulou","year":"1997","journal-title":"Eur J Immunol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3389\/fcell.2019.00091","article-title":"TNFR1 and TNFR2 in the control of the life and death balance of macrophages","volume":"7","author":"Wajant","year":"2019","journal-title":"Front Cell Dev Biol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"e12109","DOI":"10.15252\/emmm.202012109","article-title":"Aberrant upregulation of CaSR promotes pathological new bone formation in ankylosing spondylitis","volume":"12","author":"Li","year":"2020","journal-title":"EMBO Mol Med"},{"key":"B71","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/nmat4863","article-title":"The microstructure and micromechanics of the tendon-bone insertion","volume":"16","author":"Rossetti","year":"2017","journal-title":"Nat Mater"},{"key":"B72","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41584-019-0364-x","article-title":"Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis","volume":"16","author":"Gracey","year":"2020","journal-title":"Nat Rev Rheumatol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nrrheum.2017.188","article-title":"Enthesitis: from pathophysiology to treatment","volume":"13","author":"Schett","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.gaitpost.2012.10.005","article-title":"Age-related changes in spatiotemporal characteristics of gait accompany ongoing lower limb linear growth in late childhood and early adolescence","volume":"38","author":"Froehle","year":"2013","journal-title":"Gait Posture"},{"key":"B75","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1111\/j.1469-7580.2011.01461.x","article-title":"Age-related changes in mechanical properties of the Achilles tendon","volume":"220","author":"Waugh","year":"2012","journal-title":"J Anat"},{"key":"B76","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1126\/science.1095522","article-title":"An antigenic peptide produced by peptide splicing in the proteasome","volume":"304","author":"Vigneron","year":"2004","journal-title":"Science"},{"key":"B77","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/nri2687","article-title":"Proteasomes in immune cells: more than peptide producers?","volume":"10","author":"Groettrup","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/0167-5699(90)90051-A","article-title":"Guilt by association: HLA-B27 and ankylosing spondylitis","volume":"11","author":"Benjamin","year":"1990","journal-title":"Immunol Today"},{"key":"B79","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/0140-6736(93)91760-J","article-title":"HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis","volume":"342","author":"Hermann","year":"1993","journal-title":"Lancet."},{"key":"B80","doi-asserted-by":"publisher","first-page":"R521","DOI":"10.1186\/ar1221","article-title":"Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis","volume":"6","author":"Appel","year":"2004","journal-title":"Arthritis Res Ther"},{"key":"B81","first-page":"1750","article-title":"Multiple T cell expansions are found in the blood and synovial fluid of patients with reactive arthritis","volume":"24","author":"Allen","year":"1997","journal-title":"J Rheumatol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1080\/08916930902960362","article-title":"Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients","volume":"42","author":"Mamedov","year":"2009","journal-title":"Autoimmunity"},{"key":"B83","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1002\/eji.1830270205","article-title":"Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes","volume":"27","author":"Fiorillo","year":"1997","journal-title":"Eur J Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.ebiom.2019.07.032","article-title":"TCR repertoire and CDR3 motif analyses depict the role of alphabeta T cells in Ankylosing spondylitis","volume":"47","author":"Zheng","year":"2019","journal-title":"EBioMedicine"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1074\/mcp.M115.056358","article-title":"Human Leukocyte Antigen (HLA) B27 allotype-specific binding and candidate arthritogenic peptides revealed through heuristic clustering of data-independent acquisition mass spectrometry (DIA-MS) data","volume":"15","author":"Schittenhelm","year":"2016","journal-title":"Mol Cell Proteomics"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.4049\/jimmunol.170.2.1099","article-title":"CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats","volume":"170","author":"May","year":"2003","journal-title":"J Immunol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1002\/art.24599","article-title":"Spondylarthritis in HLA-B27\/human beta2-microglobulin-transgenic rats is not prevented by lack of CD8","volume":"60","author":"Taurog","year":"2009","journal-title":"Arthritis Rheum"},{"key":"B88","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1002\/art.40770","article-title":"Interleukin-17a inhibition diminishes inflammation and new bone formation in experimental spondyloarthritis","volume":"71","author":"van","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1126\/science.aaf4384","article-title":"A large fraction of HLA class I ligands are proteasome-generated spliced peptides","volume":"354","author":"Liepe","year":"2016","journal-title":"Science"},{"key":"B90","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/ng.873","article-title":"Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility","volume":"43","author":"Evans","year":"2011","journal-title":"Nat Genet"},{"key":"B91","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.immuni.2006.09.012","article-title":"ERAAP synergizes with MHC class I molecules to make the final cut in the antigenic peptide precursors in the endoplasmic reticulum","volume":"25","author":"Kanaseki","year":"2006","journal-title":"Immunity"},{"key":"B92","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.4049\/jimmunol.162.9.5045","article-title":"Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure","volume":"162","author":"Allen","year":"1999","journal-title":"J Immunol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.1002\/art.10605","article-title":"Cell-surface expression and immune receptor recognition of HLA-B27 homodimers","volume":"46","author":"Kollnberger","year":"2002","journal-title":"Arthritis Rheum"},{"key":"B94","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.4049\/jimmunol.1202926","article-title":"KIR3DL2 binds to HLA-B27 dimers and free H chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis","volume":"190","author":"Wong-Baeza","year":"2013","journal-title":"J Immunol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.1002\/art.21395","article-title":"Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis","volume":"52","author":"Chan","year":"2005","journal-title":"Arthritis Rheum"},{"key":"B96","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.4049\/jimmunol.1002653","article-title":"Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis","volume":"186","author":"Bowness","year":"2011","journal-title":"J Immunol"},{"key":"B97","doi-asserted-by":"crossref","first-page":"6665","DOI":"10.4049\/jimmunol.163.12.6665","article-title":"Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies","volume":"163","author":"Mear","year":"1999","journal-title":"J Immunol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/art.22295","article-title":"HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: Implications for the pathogenesis of spondylarthritis-like disease","volume":"56","author":"Turner","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B99","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1002\/art.24876","article-title":"Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood","volume":"60","author":"Cabral","year":"2009","journal-title":"Arthritis Rheum"},{"key":"B100","doi-asserted-by":"publisher","first-page":"17698","DOI":"10.1073\/pnas.1011736107","article-title":"Endoplasmic reticulum stress-induced transcription factor, CHOP, is crucial for dendritic cell IL-23 expression","volume":"107","author":"Goodall","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B101","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1136\/annrheumdis-2012-202925","article-title":"Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation","volume":"73","author":"Ciccia","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"B102","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1136\/annrheumdis-2012-202135","article-title":"Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model","volume":"72","author":"Van","year":"2013","journal-title":"Ann Rheum Dis."},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24174","article-title":"The phenotype of axial spondyloarthritis: is it dependent on HLA-B27 status?","author":"Coates","year":"2020","journal-title":"Arthritis Care Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jbspin.2015.03.019","article-title":"Presence of HLA-B27 is associated with changes of serum levels of mediators of the Wnt and hedgehog pathway","volume":"83","author":"Aschermann","year":"2016","journal-title":"Joint Bone Spine"},{"key":"B105","doi-asserted-by":"publisher","first-page":"5357","DOI":"10.1172\/JCI125212","article-title":"HLA-B27-mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis","volume":"129","author":"Liu","year":"2019","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","first-page":"e000451","DOI":"10.1136\/rmdopen-2017-000451","article-title":"No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA","volume":"3","author":"Neerinckx","year":"2017","journal-title":"RMD Open"},{"key":"B107","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1002\/art.21054","article-title":"Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial","volume":"52","author":"Wanders","year":"2005","journal-title":"Arthritis Rheum"},{"key":"B108","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/0006-291X(85)90611-4","article-title":"Prostaglandin E2 stimulates collagen and non-collagen protein synthesis and prolyl hydroxylase activity in osteoblastic clone MC3T3-E1 cells","volume":"126","author":"Hakeda","year":"1985","journal-title":"Biochem Biophys Res Commun"},{"key":"B109","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1677\/joe.0.1680131","article-title":"Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro","volume":"168","author":"Keila","year":"2001","journal-title":"J Endocrinol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.prostaglandins.2006.09.005","article-title":"Effects of selective prostaglandins E2 receptor agonists on cultured calvarial murine osteoblastic cells","volume":"81","author":"Alander","year":"2006","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"B111","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nrrheum.2012.37","article-title":"New advances in juvenile spondyloarthritis","volume":"8","author":"Tse","year":"2012","journal-title":"Nat Rev Rheumatol"},{"key":"B112","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/1529-0131(199805)41:5<808::AID-ART6>3.0.CO;2-T","article-title":"Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group","volume":"41","author":"van","year":"1998","journal-title":"Arthritis Rheum."},{"key":"B113","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1136\/ard.61.10.941","article-title":"A 26 week randomised, double blind, placebo controlled exploratory study of sulfasalazine in juvenile onset spondyloarthropathies","volume":"61","author":"Burgos-Vargas","year":"2002","journal-title":"Ann Rheum Dis"},{"key":"B114","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/B978-0-323-24145-8.00019-3","article-title":"Chapter 19 - Enthesitis related arthritis","volume-title":"Textbook of Pediatric Rheumatology","author":"Tse","year":"2016"},{"key":"B115","doi-asserted-by":"publisher","first-page":"2675","DOI":"10.3899\/jrheum.110427","article-title":"Attainment of inactive disease status following initiation of TNF-\u03b1 inhibitor therapy for juvenile idiopathic arthritis: enthesitis-related arthritis predicts persistent active disease","volume":"38","author":"Donnithorne","year":"2011","journal-title":"J Rheumatol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.3899\/jrheum.110145","article-title":"Tumor necrosis factor-blocking agents for children with enthesitis-related arthritis\u2013data from the dutch arthritis and biologicals in children register, 1999-2010","volume":"38","author":"Otten","year":"2011","journal-title":"J Rheumatol"},{"key":"B117","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1093\/rheumatology\/keq292","article-title":"Complete control of disease activity and remission induced by treatment with etanercept in juvenile idiopathic arthritis","volume":"50","author":"Papsdorf","year":"2011","journal-title":"Rheumatology."},{"key":"B118","first-page":"424","article-title":"Long-term outcome of anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondyloarthritis","volume":"32","author":"Hugle","year":"2014","journal-title":"Clin Exp Rheumatol"},{"key":"B119","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1097\/BOR.0000000000000399","article-title":"Janus kinase\/signal transducer and activator of transcription pathways in spondyloarthritis","volume":"29","author":"Raychaudhuri","year":"2017","journal-title":"Curr Opin Rheumatol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1136\/annrheumdis-2016-210322","article-title":"Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study","volume":"76","author":"van","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B121","first-page":"943","article-title":"Efficacy of custom foot orthotics in improving pain and functional status in children with juvenile idiopathic arthritis: a randomized trial","volume":"32","author":"Powell","year":"2005","journal-title":"J Rheumatol"},{"key":"B122","doi-asserted-by":"publisher","first-page":"e000121","DOI":"10.1136\/bmjpo-2017-000121","article-title":"Effectiveness of preformed foot orthoses in reducing lower limb pain, swollen and tender joints and in improving quality of life and gait parameters in children with juvenile idiopathic arthritis: a randomised controlled trial (Protocol)","volume":"1","author":"Fellas","year":"2017","journal-title":"BMJ Paediatr Open"},{"key":"B123","doi-asserted-by":"publisher","first-page":"600","DOI":"10.2519\/jospt.2013.4121","article-title":"A biomechanical perspective on physical therapy management of knee osteoarthritis","volume":"43","author":"Farrokhi","year":"2013","journal-title":"J Orthop Sports Phys Ther"},{"key":"B124","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nrendo.2016.12","article-title":"BMP signalling in skeletal development, disease and repair","volume":"12","author":"Salazar","year":"2016","journal-title":"Nat Rev Endocrinol"},{"key":"B125","doi-asserted-by":"publisher","first-page":"16009","DOI":"10.1038\/boneres.2016.9","article-title":"TGF-beta and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease","volume":"4","author":"Wu","year":"2016","journal-title":"Bone Res"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.666772\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T23:16:21Z","timestamp":1699053381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.666772\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":125,"alternative-id":["10.3389\/fmed.2021.666772"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.666772","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,20]]},"article-number":"666772"}}