{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T01:00:23Z","timestamp":1781312423267,"version":"3.54.1"},"reference-count":240,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including \u03b3\u03b4 T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4\/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms24076463","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T02:23:46Z","timestamp":1680143026000},"page":"6463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Uncovering the Underworld of Axial Spondyloarthritis"],"prefix":"10.3390","volume":"24","author":[{"given":"Sergio","family":"Del Vescovo","sequence":"first","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Polyclinic Hospital, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-5930","authenticated-orcid":false,"given":"Vincenzo","family":"Venerito","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Polyclinic Hospital, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5686-0127","authenticated-orcid":false,"given":"Claudia","family":"Iannone","sequence":"additional","affiliation":[{"name":"Division of Clinical Rheumatology, ASST Gaetano Pini-CTO Institute, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4524-9566","authenticated-orcid":false,"given":"Giuseppe","family":"Lopalco","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Polyclinic Hospital, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41584-020-00552-4","article-title":"Axial Spondyloarthritis: Concept, Construct, Classification and Implications for Therapy","volume":"17","author":"Robinson","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15013","DOI":"10.1038\/nrdp.2015.13","article-title":"Axial Spondyloarthritis","volume":"1","author":"Sieper","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1136\/ard.2008.101501","article-title":"New Criteria for Inflammatory Back Pain in Patients with Chronic Back Pain: A Real Patient Exercise by Experts from the Assessment of SpondyloArthritis International Society (ASAS)","volume":"68","author":"Sieper","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e12913","DOI":"10.1111\/eci.12913","article-title":"Pathophysiology of Axial Spondyloarthritis: Consensus and Controversies","volume":"48","author":"Schoones","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41590-020-00816-x","article-title":"The Immunology of Rheumatoid Arthritis","volume":"22","author":"Weyand","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13075-020-2115-4","article-title":"Innate Lymphoid Cells in Inflammatory Arthritis","volume":"22","author":"Fang","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"565275","DOI":"10.3389\/fimmu.2020.565275","article-title":"Innate Lymphocytes in Inflammatory Arthritis","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3389\/fmed.2018.00063","article-title":"Role of Subclinical Gut Inflammation in the Pathogenesis of Spondyloarthritis","volume":"5","author":"Rizzo","year":"2018","journal-title":"Front. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41584-022-00761-z","article-title":"Treatment of Axial Spondyloarthritis: An Update","volume":"18","author":"Danve","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.rdc.2012.09.003","article-title":"Epidemiology of Spondyloarthritis","volume":"38","author":"Stolwijk","year":"2012","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00281-021-00838-z","article-title":"The Enigmatic Role of HLA-B*27 in Spondyloarthritis Pathogenesis","volume":"43","author":"Navid","year":"2021","journal-title":"Semin. Immunopathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11926-017-0640-1","article-title":"An Update on the Genetic Polymorphism of HLA-B*27 With 213 Alleles Encompassing 160 Subtypes (and Still Counting)","volume":"19","author":"Khan","year":"2017","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/art.39948","article-title":"Polymorphisms in the F Pocket of HLA\u2013B27 Subtypes Strongly Affect Assembly, Chaperone Interactions, and Heavy-Chain Misfolding","volume":"69","author":"Guiliano","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ijbiomac.2016.08.066","article-title":"Differences in Conformational Stability of the Two Alpha Domains of the Disease-Associated and Non-Disease-Associated Subtypes of HLA-B27","volume":"94","author":"Rana","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1093\/rheumatology\/ket219","article-title":"The Arthritis-Associated HLA-B*27:05 Allele Forms More Cell Surface B27 Dimer and Free Heavy Chain Ligands for KIR3DL2 than HLA-B*27:09","volume":"52","author":"Cauli","year":"2013","journal-title":"Rheumatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20185","DOI":"10.1074\/jbc.RA119.010257","article-title":"Allelic Association with Ankylosing Spondylitis Fails to Correlate with Human Leukocyte Antigen B27 Homodimer Formation","volume":"294","author":"Indumathy","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/art.39567","article-title":"Increased Conformational Flexibility of HLA\u2013B*27 Subtypes Associated With Ankylosing Spondylitis","volume":"68","author":"Loll","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3389\/fimmu.2020.00179","article-title":"Conformational Plasticity of HLA-B27 Molecules Correlates Inversely With Efficiency of Negative T Cell Selection","volume":"11","author":"Loll","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s13238-012-2077-7","article-title":"Recognition of Self and Altered Self by T Cells in Autoimmunity and Allergy","volume":"4","author":"Yin","year":"2013","journal-title":"Protein Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1136\/jcp.40.9.948","article-title":"The HLA System: Structure and Function","volume":"40","author":"Bodmer","year":"1987","journal-title":"J. Clin. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1136\/ard.60.4.316","article-title":"Immunohistological Study of Entheses in Spondyloarthropathies: Comparison in Rheumatoid Arthritis and Osteoarthritis","volume":"60","author":"Laloux","year":"2001","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1002\/art.41129","article-title":"Altered Cytotoxicity Profile of CD8+ T Cells in Ankylosing Spondylitis","volume":"72","author":"Gracey","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1002\/art.20948","article-title":"HLA\u2013B27\u2013Restricted CD8+ T Cell Response to Cartilage-Derived Self Peptides in Ankylosing Spondylitis","volume":"52","author":"Atagunduz","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1136\/annrheumdis-2015-208677","article-title":"Genetic Association of Ankylosing Spondylitis with TBX21 Influences T-Bet and pro-Inflammatory Cytokine Expression in Humans and SKG Mice as a Model of Spondyloarthritis","volume":"76","author":"Lau","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/art.40028","article-title":"Discovery of T Cell Receptor \u03b2 Motifs Specific to HLA-B27-Positive Ankylosing Spondylitis by Deep Repertoire Sequence Analysis","volume":"69","author":"Faham","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/art.41252","article-title":"Altered Repertoire Diversity and Disease-Associated Clonal Expansions Revealed by T Cell Receptor Immunosequencing in Ankylosing Spondylitis Patients","volume":"72","author":"Hanson","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/ncb0805-766","article-title":"ERAD: The Long Road to Destruction","volume":"7","author":"Meusser","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1002\/art.38809","article-title":"Endoplasmic Reticulum Degradation\u2013Enhancing \u03b1-Mannosidase\u2013like Protein 1 Targets Misfolded HLA\u2013B27 Dimers for Endoplasmic Reticulum\u2013Associated Degradation","volume":"66","author":"Guiliano","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrrheum.2016.192","article-title":"Causes and Consequences of Endoplasmic Reticulum Stress in Rheumatic Disease","volume":"13","author":"Navid","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","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":"ref_31","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.4049\/jimmunol.175.4.2438","article-title":"HLA-B27 Misfolding in Transgenic Rats Is Associated with Activation of the Unfolded Protein Response","volume":"175","author":"Turner","year":"2005","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1002\/art.24763","article-title":"HLA\u2013B27 Misfolding and the Unfolded Protein Response Augment Interleukin-23 Production and Are Associated with Th17 Activation in Transgenic Rats","volume":"60","author":"DeLay","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s10753-021-01575-z","article-title":"Upregulation of Unfolded Protein Response and ER Stress-Related IL-23 Production in M1 Macrophages from Ankylosing Spondylitis Patients","volume":"45","author":"Rezaiemanesh","year":"2022","journal-title":"Inflammation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"rky014","DOI":"10.1093\/rap\/rky014","article-title":"Altered Cytokine Expression by Macrophages from HLA-B27-Positive Spondyloarthritis Patients without Evidence of Endoplasmic Reticulum Stress","volume":"2","author":"Ambarus","year":"2018","journal-title":"Rheumatol. Adv. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","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":"ref_36","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/art.40414","article-title":"The Role of Autophagy in the Degradation of Misfolded HLA-B27 Heavy Chains","volume":"70","author":"Navid","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"795053","DOI":"10.3389\/fimmu.2021.795053","article-title":"Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27","volume":"12","author":"Thakur","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1002\/eji.200323678","article-title":"Lymphoblastoid Cells Express HLA-B27 Homodimers Both Intracellularly and at the Cell Surface Following Endosomal Recycling","volume":"33","author":"Bird","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Hatano, H., Shaw, J., Olde Nordkamp, M., Jiang, G., Li, D., and Kollnberger, S. (2015). The Leukocyte Immunoglobulin-Like Receptor Family Member LILRB5 Binds to HLA-Class I Heavy Chains. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129063"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/eji.200635997","article-title":"Interaction of HLA-B27 Homodimers with KIR3DL1 and KIR3DL2, Unlike HLA-B27 Heterotrimers, Is Independent of the Sequence of Bound Peptide","volume":"37","author":"Kollnberger","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","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":"Ridley","year":"2013","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","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":"ref_43","doi-asserted-by":"crossref","unstructured":"Yu, H.-C., Huang, K.-Y., Lu, M.-C., Huang Tseng, H.-Y., Liu, S.-Q., Lai, N.-S., and Huang, H.-B. (2022). HLA-B*27 Heavy Chain Homo-Oligomers Promote the Cytotoxicity of NK Cells via Activation of PI3K\/AKT Signaling. Medicina, 58.","DOI":"10.3390\/medicina58101411"},{"key":"ref_44","doi-asserted-by":"crossref","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":"ref_45","doi-asserted-by":"crossref","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":"ref_46","doi-asserted-by":"crossref","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":"Jt. Bone Spine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1136\/annrheumdis-2019-215832","article-title":"HLA-B27 Alters BMP\/TGF\u03b2 Signalling in Drosophila, Revealing Putative Pathogenic Mechanism for Spondyloarthritis","volume":"78","author":"Grandon","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5357","DOI":"10.1172\/JCI125212","article-title":"HLA-B27\u2013Mediated Activation of TNAP Phosphatase Promotes Pathogenic Syndesmophyte Formation in Ankylosing Spondylitis","volume":"129","author":"Liu","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jaut.2016.12.008","article-title":"Separate Effects of the Ankylosing Spondylitis Associated ERAP1 and ERAP2 Aminopeptidases Determine the Influence of Their Combined Phenotype on the HLA-B*27 Peptidome","volume":"79","author":"Guasp","year":"2017","journal-title":"J. Autoimmun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.3389\/fimmu.2018.02463","article-title":"How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins","volume":"9","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"BSR20171503","DOI":"10.1042\/BSR20171503","article-title":"The Role of Polymorphic ERAP1 in Autoinflammatory Disease","volume":"38","author":"Reeves","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7146","DOI":"10.1038\/ncomms8146","article-title":"Major Histocompatibility Complex Associations of Ankylosing Spondylitis Are Complex and Involve Further Epistasis with ERAP1","volume":"6","author":"Cortes","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/ng.2007.17","article-title":"Association Scan of 14,500 Nonsynonymous SNPs in Four Diseases Identifies Autoimmunity Variants","volume":"39","author":"Burton","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1074\/mcp.M116.066241","article-title":"The Human Leukocyte Antigen (HLA)-B27 Peptidome in Vivo, in Spondyloarthritis-Susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion","volume":"16","author":"Barnea","year":"2017","journal-title":"Mol. Cell. Proteom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17594","DOI":"10.1073\/pnas.1408882111","article-title":"Functionally Distinct ERAP1 Allotype Combinations Distinguish Individuals with Ankylosing Spondylitis","volume":"111","author":"Reeves","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1136\/annrheumdis-2011-200347","article-title":"Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Exhibits Functionally Significant Interaction with HLA-B27 and Relates to Subtype Specificity in Ankylosing Spondylitis","volume":"71","author":"Haroon","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1136\/annrheumdis-2014-206996","article-title":"Silencing or Inhibition of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Suppresses Free Heavy Chain Expression and Th17 Responses in Ankylosing Spondylitis","volume":"75","author":"Chen","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.molimm.2016.04.002","article-title":"ERAP1 Reduces Accumulation of Aberrant and Disulfide-Linked Forms of HLA-B27 on the Cell Surface","volume":"74","author":"Tran","year":"2016","journal-title":"Mol. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/gene.2014.62","article-title":"Disease-Associated Polymorphisms in ERAP1 Do Not Alter Endoplasmic Reticulum Stress in Patients with Ankylosing Spondylitis","volume":"16","author":"Kenna","year":"2015","journal-title":"Genes Immun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/art.33396","article-title":"Interleukin-17-Positive Mast Cells Contribute to Synovial Inflammation in Spondylarthritis","volume":"64","author":"Noordenbos","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1189\/jlb.3HI1215-542R","article-title":"Human Mast Cells Capture, Store, and Release Bioactive, Exogenous IL-17A","volume":"100","author":"Noordenbos","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12967-016-1050-2","article-title":"A Proof-of-Concept Study with the Tyrosine Kinase Inhibitor Nilotinib in Spondyloarthritis","volume":"14","author":"Paramarta","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"861459","DOI":"10.3389\/fimmu.2022.861459","article-title":"Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis","volume":"13","author":"Jiang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1002\/art.42090","article-title":"Characterization of Blood Mucosal-Associated Invariant T Cells in Patients with Axial Spondyloarthritis and of Resident Mucosal-Associated Invariant T Cells From the Axial Entheses of Non-Axial Spondyloarthritis Control Patients","volume":"74","author":"Rosine","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"R95","DOI":"10.1186\/ar3370","article-title":"Analysis of IL-17(+) 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","volume":"13","author":"Appel","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/eji.202048878","article-title":"IL-17A Expressed on Neutrophil Extracellular Traps Promotes Mesenchymal Stem Cell Differentiation toward Bone-Forming Cells in Ankylosing Spondylitis","volume":"51","author":"Papagoras","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/1756-185X.14057","article-title":"Neutrophil Extracellular Traps and Inflammatory Response: Implications for the Immunopathogenesis of Ankylosing Spondylitis","volume":"24","year":"2021","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12929-020-00634-1","article-title":"Enhanced NETosis Generation in Radiographic Axial Spondyloarthritis: Utility as Biomarker for Disease Activity and Anti-TNF-\u03b1 Therapy Effectiveness","volume":"27","author":"Barbarroja","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_69","first-page":"33","article-title":"The Role of NETosis in Systemic Lupus Erythematosus","volume":"1","author":"Salemme","year":"2019","journal-title":"J. Cell. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1136\/ard.59.2.135","article-title":"Quantitative Analyses of Sacroiliac Biopsies in Spondyloarthropathies: T Cells and Macrophages Predominate in Early and Active Sacroiliitis- Cellularity Correlates with the Degree of Enhancement Detected by Magnetic Resonance Imaging","volume":"59","author":"Bollow","year":"2000","journal-title":"Ann. Rheum. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17842","DOI":"10.1038\/s41598-021-96262-2","article-title":"Monocyte-Derived and M1 Macrophages from Ankylosing Spondylitis Patients Released Higher TNF-\u03b1 and Expressed More IL1B in Response to BzATP than Macrophages from Healthy Subjects","volume":"11","author":"Akhtari","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","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":"ref_73","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1002\/art.40582","article-title":"Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor-Like Molecule 1A+Interleukin-23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and Modulate Innate Lymphoid Cell 3 Immune Functions","volume":"70","author":"Ciccia","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1111\/apm.12757","article-title":"M2 Polarization of Monocytes in Ankylosing Spondylitis and Relationship with Inflammation and Structural Damage","volume":"125","author":"Zhao","year":"2017","journal-title":"APMIS"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41420-022-00900-1","article-title":"Transfer of MicroRNA-22-3p by M2 Macrophage-Derived Extracellular Vesicles Facilitates the Development of Ankylosing Spondylitis through the PER2-Mediated Wnt\/\u03b2-Catenin Axis","volume":"8","author":"Liu","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1002\/art.40175","article-title":"Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis","volume":"69","author":"Ranganathan","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.drudis.2018.06.017","article-title":"Small-Molecule Inhibitors of Macrophage Migration Inhibitory Factor (MIF) as an Emerging Class of Therapeutics for Immune Disorders","volume":"23","author":"Kok","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1126\/science.aaz8777","article-title":"Trained ILC3 Responses Promote Intestinal Defense","volume":"375","author":"Serafini","year":"2022","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"789788","DOI":"10.3389\/fimmu.2021.789788","article-title":"Innate Lymphoid Cells in Autoimmune Diseases","volume":"12","author":"Clottu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fimmu.2012.00072","article-title":"Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells","volume":"3","author":"Hoorweg","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1084\/jem.20140678","article-title":"CX3CR1+ Mononuclear Phagocytes Support Colitis-Associated Innate Lymphoid Cell Production of IL-22","volume":"211","author":"Longman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1002\/art.40150","article-title":"Brief Report: Group 3 Innate Lymphoid Cells in Human Enthesis","volume":"69","author":"Cuthbert","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1136\/annrheumdis-2014-206323","article-title":"Type 3 Innate Lymphoid Cells Producing IL-17 and IL-22 Are Expanded in the Gut, in the Peripheral Blood, Synovial Fluid and Bone Marrow of Patients with Ankylosing Spondylitis","volume":"74","author":"Ciccia","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"553742","DOI":"10.3389\/fimmu.2020.553742","article-title":"Innate Cells: The Alternative Source of IL-17 in Axial and Peripheral Spondyloarthritis?","volume":"11","author":"Rosine","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1136\/annrheumdis-2016-209695","article-title":"MAIT Cells: Not Just Another Brick in the Wall","volume":"75","author":"Debusschere","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e000821","DOI":"10.1136\/rmdopen-2018-000821","article-title":"MAIT Cells: Potent Major Cellular Players in the IL-17 Pathway of Spondyloarthritis?","volume":"4","author":"Toussirot","year":"2018","journal-title":"RMD Open"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1136\/annrheumdis-2015-208902","article-title":"IL-7 Primes IL-17 in Mucosal-Associated Invariant T (MAIT) Cells, Which Contribute to the Th17-Axis in Ankylosing Spondylitis","volume":"75","author":"Gracey","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.3899\/jrheum.151133","article-title":"Involvement of Mucosal-Associated Invariant T Cells in Ankylosing Spondylitis","volume":"43","author":"Hayashi","year":"2016","journal-title":"J. Rheumatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.3389\/fimmu.2018.01610","article-title":"Increased IL-22- and IL-17A-Producing Mucosal-Associated Invariant T Cells in the Peripheral Blood of Patients With Ankylosing Spondylitis","volume":"9","author":"Toussirot","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"127","DOI":"10.12688\/f1000research.21378.1","article-title":"Recent Advances in INKT Cell Development","volume":"9","author":"Hogquist","year":"2020","journal-title":"F1000Research"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1002\/art.27324","article-title":"Invariant Natural Killer T Cells Are Natural Regulators of Murine Spondylarthritis","volume":"62","author":"Jacques","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3389\/fcimb.2017.00398","article-title":"Activation of INKT Cells Prevents Salmonella-Enterocolitis and Salmonella-Induced Reactive Arthritis by Downregulating IL-17-Producing \u0393\u03b4T Cells","volume":"7","author":"Sarnacki","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41467-018-07911-6","article-title":"ROR\u03b3t Inhibition Selectively Targets IL-17 Producing INKT and \u0393\u03b4-T Cells Enriched in Spondyloarthritis Patients","volume":"10","author":"Venken","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/imm.12993","article-title":"Interleukin-17-Producing \u0393\u03b4 T (\u0393\u03b417) Cells in Inflammatory Diseases","volume":"155","author":"Akitsu","year":"2018","journal-title":"Immunology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/art.33507","article-title":"Enrichment of Circulating Interleukin-17-Secreting Interleukin-23 Receptor-Positive \u03b3\/\u03b4 T Cells in Patients with Active Ankylosing Spondylitis","volume":"64","author":"Kenna","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1136\/annrheumdis-2019-215210","article-title":"Evidence That Tissue Resident Human Enthesis \u0393\u03b4T-Cells Can Produce IL-17A Independently of IL-23R Transcript Expression","volume":"78","author":"Cuthbert","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nm.2817","article-title":"IL-23 Induces Spondyloarthropathy by Acting on ROR-\u0393t+ CD3+CD4-CD8- Entheseal Resident T Cells","volume":"18","author":"Sherlock","year":"2012","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1002\/art.39732","article-title":"Interleukin-23-Dependent \u03b3\/\u03b4 T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice","volume":"68","author":"Reinhardt","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/rheumatology\/kez364","article-title":"Differential Expression of TLR2 and TLR4 in A4\u03b27-Positive Leukocytes of Patients with Axial Spondyloarthritis","volume":"59","year":"2020","journal-title":"Rheumatology"},{"key":"ref_100","doi-asserted-by":"crossref","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":"ref_101","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1002\/art.34423","article-title":"\u03b2-Glucan Triggers Spondylarthritis and Crohn\u2019s Disease\u2013like Ileitis in SKG Mice","volume":"64","author":"Ruutu","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/35006664","article-title":"The Duration of Antigen Receptor Signalling Determines CD4+ versus CD8+ T-Cell Lineage Fate","volume":"404","author":"Yasutomo","year":"2000","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/ni.1860","article-title":"The Zinc-Finger Protein MAZR Is Part of the Transcription Factor Network That Controls the CD4 versus CD8 Lineage Fate of Double-Positive Thymocytes","volume":"11","author":"Sakaguchi","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.ebiom.2019.07.032","article-title":"TCR Repertoire and CDR3 Motif Analyses Depict the Role of A\u03b2 T Cells in Ankylosing Spondylitis","volume":"47","author":"Zheng","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"973243","DOI":"10.3389\/fimmu.2022.973243","article-title":"TCR Repertoire Profiling Revealed Antigen-Driven CD8+ T Cell Clonal Groups Shared in Synovial Fluid of Patients with Spondyloarthritis","volume":"13","author":"Komech","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s13075-020-02226-8","article-title":"TNF-\u03b1 Inhibitor Therapy Can Improve the Immune Imbalance of CD4+ T Cells and Negative Regulatory Cells but Not CD8+ T Cells in Ankylosing Spondylitis","volume":"22","author":"Yang","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"696973","DOI":"10.3389\/fimmu.2021.696973","article-title":"Imbalance of Peripheral Lymphocyte Subsets in Patients with Ankylosing Spondylitis: A Meta-Analysis","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e13190","DOI":"10.1111\/sji.13190","article-title":"Increased Proportions of Inflammatory T Cells and Their Correlations with Cytokines and Clinical Parameters in Patients with Ankylosing Spondylitis from Northern Sweden","volume":"96","author":"Lejon","year":"2022","journal-title":"Scand. J. Immunol."},{"key":"ref_109","first-page":"8709804","article-title":"Meta-Analysis of Changes in the Number and Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis","volume":"2020","author":"Li","year":"2020","journal-title":"Biomed Res. Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/art.39464","article-title":"Sexual Dimorphism in the Th17 Signature of Ankylosing Spondylitis","volume":"68","author":"Gracey","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/rheumatology\/kes267","article-title":"Decreased Th17 and Th1 Cells in the Peripheral Blood of Patients with Early Non-Radiographic Axial Spondyloarthritis: A Marker of Disease Activity in HLA-B27+ Patients","volume":"52","author":"Peiteado","year":"2013","journal-title":"Rheumatology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00281-019-00733-8","article-title":"The Pathogenicity of Th17 Cells in Autoimmune Diseases","volume":"41","author":"Yasuda","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"iv79","DOI":"10.1093\/rheumatology\/keaa435","article-title":"Treatment Strategies in Axial Spondyloarthritis: What, When and How?","volume":"59","author":"Fragoulis","year":"2020","journal-title":"Rheumatology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s13075-019-1948-1","article-title":"Prostaglandin Receptor EP4 Expression by Th17 Cells Is Associated with High Disease Activity in Ankylosing Spondylitis","volume":"21","author":"Klasen","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e174","DOI":"10.1136\/annrheumdis-2019-216456","article-title":"Gut-Derived CD8(+) Tissue-Resident Memory T Cells Are Expanded in the Peripheral Blood and Synovia of SpA Patients","volume":"80","author":"Guggino","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1136\/annrheumdis-2019-215349","article-title":"Integrin and Transcriptomic Profiles Identify a Distinctive Synovial CD8+ T Cell Subpopulation in Spondyloarthritis","volume":"78","author":"Qaiyum","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41413-019-0057-8","article-title":"Ankylosing Spondylitis: Etiology, Pathogenesis, and Treatments","volume":"7","author":"Zhu","year":"2019","journal-title":"Bone Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.intimp.2018.03.032","article-title":"Dysfunction of Regulatory T Cells in Patients with Ankylosing Spondylitis Is Associated with a Loss of Tim-3","volume":"59","author":"Wang","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s11926-018-0729-1","article-title":"Functional Defects of Treg Cells: New Targets in Rheumatic Diseases, Including Ankylosing Spondylitis","volume":"20","author":"Miao","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.3389\/fimmu.2020.02151","article-title":"Semaphorin 4D Induces an Imbalance of Th17\/Treg Cells by Activating the Aryl Hydrocarbon Receptor in Ankylosing Spondylitis","volume":"11","author":"Xie","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e6605","DOI":"10.1097\/MD.0000000000006605","article-title":"Immunohistological Analysis of Active Sacroiliitis in Patients with Axial Spondyloarthritis","volume":"96","author":"Peng","year":"2017","journal-title":"Medicine"},{"key":"ref_122","first-page":"1784","article-title":"Value of the Peripheral Blood B-Cells Subsets in Patients with Ankylosing Spondylitis","volume":"122","author":"Lin","year":"2009","journal-title":"Chin. Med. J."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Bautista-Caro, M.-B., de Miguel, E., Peiteado, D., Plasencia-Rodr\u00edguez, C., Villalba, A., Monjo-Henry, I., Puig-Kr\u00f6ger, A., S\u00e1nchez-Mateos, P., Mart\u00edn-Mola, E., and Miranda-Car\u00fas, M.-E. (2017). Increased Frequency of Circulating CD19+CD24hiCD38hi B Cells with Regulatory Capacity in Patients with Ankylosing Spondylitis (AS) Na\u00efve for Biological Agents. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180726"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1089\/dna.2015.3046","article-title":"Defective Function of CD24(+)CD38(+) Regulatory B Cells in Ankylosing Spondylitis","volume":"35","author":"Chen","year":"2016","journal-title":"DNA Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Wilbrink, R., Spoorenberg, A., Verstappen, G.M.P.J., and Kroese, F.G.M. (2021). B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413325"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.jbspin.2008.01.023","article-title":"Lack of Short-Term Efficacy of Rituximab upon Symptoms of Ankylosing Spondylitis Treated for an Associated Vasculitis","volume":"75","author":"Wendling","year":"2008","journal-title":"Jt. Bone Spine"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1136\/annrheumdis-2012-201926","article-title":"One-Year Follow-up of Ankylosing Spondylitis Patients Responding to Rituximab Treatment and Re-Treated in Case of a Flare","volume":"72","author":"Song","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/art.27383","article-title":"Different Response to Rituximab in Tumor Necrosis Factor Blocker-Naive Patients with Active Ankylosing Spondylitis and in Patients in Whom Tumor Necrosis Factor Blockers Have Failed: A Twenty-Four-Week Clinical Trial","volume":"62","author":"Song","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00011-016-0995-1","article-title":"The Biological Function and Significance of CD74 in Immune Diseases","volume":"66","author":"Su","year":"2017","journal-title":"Inflamm. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/eji.201948502","article-title":"Impaired Proteolysis by SPPL2a Causes CD74 Fragment Accumulation That Can Be Recognized by Anti-CD74 Autoantibodies in Human Ankylosing Spondylitis","volume":"50","author":"Leijten","year":"2020","journal-title":"Eur. J. Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1136\/annrheumdis-2012-202177","article-title":"High Prevalence of Anti-CD74 Antibodies Specific for the HLA Class II-Associated Invariant Chain Peptide (CLIP) in Patients with Axial Spondyloarthritis","volume":"73","author":"Baraliakos","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Puccetti, A., Dolcino, M., Tinazzi, E., Moretta, F., D\u2019Angelo, S., Olivieri, I., and Lunardi, C. (2017). Antibodies Directed against a Peptide Epitope of a Klebsiella Pneumoniae-Derived Protein Are Present in Ankylosing Spondylitis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171073"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1136\/annrheumdis-2013-203630","article-title":"Serum Levels of Novel Noggin and Sclerostin-Immune Complexes Are Elevated in Ankylosing Spondylitis","volume":"73","author":"Tsui","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/s00774-020-01176-0","article-title":"Sclerostin: From Bench to Bedside","volume":"39","author":"Tanaka","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.biocel.2011.01.007","article-title":"Noggin","volume":"43","author":"Krause","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_136","doi-asserted-by":"crossref","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":"ref_137","doi-asserted-by":"crossref","unstructured":"Jang, D.-I., Lee, A.-H., Shin, H.-Y., Song, H.-R., Park, J.-H., Kang, T.-B., Lee, S.-R., and Yang, S.-H. (2021). The Role of Tumor Necrosis Factor Alpha (TNF-\u03b1) in Autoimmune Disease and Current TNF-\u03b1 Inhibitors in Therapeutics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052719"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/path.2287","article-title":"TNF-Mediated Inflammatory Disease","volume":"214","author":"Bradley","year":"2008","journal-title":"J. Pathol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/art.1780380407","article-title":"Use of Immunohistologic and in Situ Hybridization Techniques in the Examination of Sacroiliac Joint Biopsy Specimens from Patients with Ankylosing Spondylitis","volume":"38","author":"Braun","year":"1995","journal-title":"Arthritis Rheum."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"31","DOI":"10.22631\/rr.2017.69997.1014","article-title":"Gene Expression Profile of Proinflammatory Cytokines in Iranian Patients with Ankylosing Spondylitis","volume":"2","author":"Asadbeik","year":"2017","journal-title":"Rheumatol. Res."},{"key":"ref_141","doi-asserted-by":"crossref","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":"Geka","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0140-6736(18)31362-X","article-title":"Efficacy and Safety of Continuing versus Withdrawing Adalimumab Therapy in Maintaining Remission in Patients with Non-Radiographic Axial Spondyloarthritis (ABILITY-3): A Multicentre, Randomised, Double-Blind Study","volume":"392","author":"Sieper","year":"2018","journal-title":"Lancet"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1136\/annrheumdis-2012-201766","article-title":"Efficacy and Safety of Adalimumab in Patients with Non-Radiographic Axial Spondyloarthritis: Results of a Randomised Placebo-Controlled Trial (ABILITY-1)","volume":"72","author":"Sieper","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1080\/14712598.2017.1347156","article-title":"Etanercept for Treating Axial Spondyloarthritis","volume":"17","author":"Guillot","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1759720X20987700","DOI":"10.1177\/1759720X20987700","article-title":"Sustained Clinical Response and Safety of Etanercept in Patients with Early Axial Spondyloarthritis: 10-Year Results of the ESTHER Trial","volume":"13","author":"Proft","year":"2021","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3402","DOI":"10.1002\/art.23969","article-title":"Efficacy and Safety of Golimumab in Patients with Ankylosing Spondylitis: Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial","volume":"58","author":"Inman","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.cyto.2016.08.014","article-title":"Molecular Mechanisms of Action of Anti-TNF-\u03b1 Agents\u2014Comparison among Therapeutic TNF-\u03b1 Antagonists","volume":"101","author":"Mitoma","year":"2018","journal-title":"Cytokine"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/art.20852","article-title":"Efficacy and Safety of Infliximab in Patients with Ankylosing Spondylitis: Results of a Randomized, Placebo-Controlled Trial (ASSERT)","volume":"52","author":"Dijkmans","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1136\/annrheumdis-2017-212377","article-title":"Limited Radiographic Progression and Sustained Reductions in MRI Inflammation in Patients with Axial Spondyloarthritis: 4-Year Imaging Outcomes from the RAPID-AxSpA Phase III Randomised Trial","volume":"77","author":"Baraliakos","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/art.41667","article-title":"Tumor Necrosis Factor Inhibitors Reduce Spinal Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: A Longitudinal Analysis From the Alberta Prospective Cohort","volume":"73","author":"Sepriano","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/art.41206","article-title":"3rd Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis","volume":"72","author":"Karmacharya","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"a028522","DOI":"10.1101\/cshperspect.a028522","article-title":"Interleukin 17 Family Cytokines: Signaling Mechanisms, Biological Activities, and Therapeutic Implications","volume":"10","author":"Monin","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1172\/JCI78085","article-title":"Pouring Fuel on the Fire: Th17 Cells, the Environment, and Autoimmunity","volume":"125","author":"Burkett","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nm.3883","article-title":"The Emerging Role of Resident Memory T Cells in Protective Immunity and Inflammatory Disease","volume":"21","author":"Park","year":"2015","journal-title":"Nat. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1038\/jid.2014.261","article-title":"The IL-17A-Producing CD8+ T-Cell Population in Psoriatic Lesional Skin Comprises Mucosa-Associated Invariant T Cells and Conventional T Cells","volume":"134","author":"Teunissen","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.4049\/jimmunol.0903271","article-title":"IL-17 Contributes to Angiogenesis in Rheumatoid Arthritis","volume":"184","author":"Pickens","year":"2010","journal-title":"J. Immunol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Tsukazaki, H., and Kaito, T. (2020). The Role of the IL-23\/IL-17 Pathway in the Pathogenesis of Spondyloarthritis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176401"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"637829","DOI":"10.3389\/fimmu.2021.637829","article-title":"Role of the IL-23\/IL-17 Pathway in Rheumatic Diseases: An Overview","volume":"12","author":"Schinocca","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41584-019-0294-7","article-title":"The IL-23-IL-17 Pathway as a Therapeutic Target in Axial Spondyloarthritis","volume":"15","author":"Sieper","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Danoy, P., Pryce, K., Hadler, J., Bradbury, L.A., Farrar, C., Pointon, J., Ward, M., Weisman, M., Reveille, J.D., and Wordsworth, B.P. (2010). Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn\u2019s Disease. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001195"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"70310","DOI":"10.18632\/oncotarget.20319","article-title":"IL-23R and IL-17A Polymorphisms Correlate with Susceptibility of Ankylosing Spondylitis in a Southwest Chinese Population","volume":"8","author":"Yang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_162","first-page":"3125922","article-title":"Polymorphisms within Genes Coding for IL-17A and F and Their Receptor as Clinical Hallmarks in Ankylosing Spondylitis","volume":"2021","author":"Kolossa","year":"2021","journal-title":"Mediators Inflamm."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ng.2667","article-title":"Identification of Multiple Risk Variants for Ankylosing Spondylitis through High-Density Genotyping of Immune-Related Loci","volume":"45","author":"Cortes","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1007\/s12325-022-02240-z","article-title":"Levels of Peripheral Th17 Cells and Th17-Related Cytokines in Patients with Ankylosing Spondylitis: A Meta-Analysis","volume":"39","author":"Su","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/art.1780350911","article-title":"Appendicular and Vertebral Bone Mass in Ankylosing Spondylitis. A Comparison of Plain Radiographs with Single- and Dual-Photon Absorptiometry and with Quantitative Computed Tomography","volume":"35","author":"Devogelaer","year":"1992","journal-title":"Arthritis Rheum."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1152\/physrev.00036.2016","article-title":"Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems","volume":"97","author":"Okamoto","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/03008207.2020.1759562","article-title":"RANKL Expression of Primary Osteoblasts Is Enhanced by an IL-17-Mediated JAK2\/STAT3 Pathway through Autophagy Suppression","volume":"62","author":"Wang","year":"2021","journal-title":"Connect. Tissue Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"10928","DOI":"10.1038\/ncomms10928","article-title":"IL-17-Producing \u0393\u03b4 T Cells Enhance Bone Regeneration","volume":"7","author":"Ono","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_169","doi-asserted-by":"crossref","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":"ref_170","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3389\/fimmu.2014.00425","article-title":"Effects of Interleukin-17A on Osteogenic Differentiation of Isolated Human Mesenchymal Stem Cells","volume":"5","author":"Osta","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41584-018-0091-8","article-title":"Effects of the IL-23-IL-17 Pathway on Bone in Spondyloarthritis","volume":"14","author":"Gravallese","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"96993","DOI":"10.18632\/oncotarget.20823","article-title":"Interleukin-17A-Promoted MSC2 Polarization Related with New Bone Formation of Ankylosing Spondylitis","volume":"8","author":"He","year":"2017","journal-title":"Oncotarget"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13075-018-1582-3","article-title":"IL-17A Induces Osteoblast Differentiation by Activating JAK2\/STAT3 in Ankylosing Spondylitis","volume":"20","author":"Jo","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Daoussis, D., Kanellou, A., Panagiotopoulos, E., and Papachristou, D. (2022). DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126660"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/art.38896","article-title":"Combined Inhibition of Tumor Necrosis Factor \u03b1 and Interleukin-17 as a Therapeutic Opportunity in Rheumatoid Arthritis: Development and Characterization of a Novel Bispecific Antibody","volume":"67","author":"Fischer","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_176","doi-asserted-by":"crossref","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":"ref_177","doi-asserted-by":"crossref","first-page":"L1283","DOI":"10.1152\/ajplung.00367.2005","article-title":"IL-17A Acts via P38 MAPK to Increase Stability of TNF-Alpha-Induced IL-8 MRNA in Human ASM","volume":"290","author":"Henness","year":"2006","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10067-019-04749-1","article-title":"The Important Role of Central Sensitization in Chronic Musculoskeletal Pain Seen in Different Rheumatic Diseases","volume":"39","author":"Guler","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"151933","DOI":"10.1016\/j.semarthrit.2021.11.006","article-title":"Central Sensitization Has Major Impact on Quality of Life in Patients with Axial Spondyloarthritis","volume":"52","author":"Kieskamp","year":"2022","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_180","first-page":"481","article-title":"The Relationship between Central Sensitization and Disease Activity, Quality of Life, and Sleep Quality among Patients with Axial Spondyloarthritis","volume":"192","year":"2022","journal-title":"Irish J. Med. Sci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s40122-021-00310-8","article-title":"Assessment of Neuropathic Pain in Ankylosing Spondylitis: Prevalence and Characteristics","volume":"10","author":"Zhou","year":"2021","journal-title":"Pain Ther."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1080\/14397595.2020.1754322","article-title":"Neuropathic Component of Low Back Pain in Patients with Ankylosing Spondylitis","volume":"31","author":"Borman","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_183","first-page":"324","article-title":"Neuropathic Pain Component in Axial Spondyloarthritis and the Influence on Disease Burden","volume":"24","author":"Gok","year":"2018","journal-title":"J. Clin. Rheumatol. Pract. Rep. Rheum. Musculoskelet. Dis."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00393-019-0654-3","article-title":"Neuropathic Pain in Ankylosing Spondylitis: A Meta-Analysis","volume":"79","author":"Kim","year":"2020","journal-title":"Z. Rheumatol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.pain.2009.11.006","article-title":"IL-17 Mediates Articular Hypernociception in Antigen-Induced Arthritis in Mice","volume":"148","author":"Pinto","year":"2010","journal-title":"Pain"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.it.2016.10.001","article-title":"Nociceptor Sensory Neuron\u2013Immune Interactions in Pain and Inflammation","volume":"38","author":"Verri","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1002\/art.37695","article-title":"Interleukin-17 Sensitizes Joint Nociceptors to Mechanical Stimuli and Contributes to Arthritic Pain through Neuronal Interleukin-17 Receptors in Rodents","volume":"64","author":"Richter","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"10334","DOI":"10.1038\/s41598-017-10509-5","article-title":"Interleukin-17A Is Involved in Mechanical Hyperalgesia but Not in the Severity of Murine Antigen-Induced Arthritis","volume":"7","author":"Ebbinghaus","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.mcn.2012.11.006","article-title":"Neuronal IL-17 Receptor Upregulates TRPV4 but Not TRPV1 Receptors in DRG Neurons and Mediates Mechanical but Not Thermal Hyperalgesia","volume":"52","author":"Boettger","year":"2013","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pain.2012.10.022","article-title":"Spinal Interleukin-17 Promotes Thermal Hyperalgesia and NMDA NR1 Phosphorylation in an Inflammatory Pain Rat Model","volume":"154","author":"Meng","year":"2013","journal-title":"Pain"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1136\/annrheumdis-2016-210023","article-title":"Secukinumab Efficacy in Anti-TNF-Naive and Anti-TNF-Experienced Subjects with Active Ankylosing Spondylitis: Results from the MEASURE 2 Study","volume":"76","author":"Sieper","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1080\/14397595.2018.1538004","article-title":"Efficacy and Safety of Secukinumab in Japanese Patients with Active Ankylosing Spondylitis: 24-Week Results from an Open-Label Phase 3 Study (MEASURE 2-J)","volume":"30","author":"Kishimoto","year":"2020","journal-title":"Mod. Rheumatol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s40744-018-0123-5","article-title":"Efficacy and Safety of Secukinumab 150 Mg with and Without Loading Regimen in Ankylosing Spondylitis: 104-Week Results from MEASURE 4 Study","volume":"5","author":"Kivitz","year":"2018","journal-title":"Rheumatol. Ther."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"e001005","DOI":"10.1136\/rmdopen-2019-001005","article-title":"Long-Term Efficacy and Safety of Secukinumab 150 Mg in Ankylosing Spondylitis: 5-Year Results from the Phase III MEASURE 1 Extension Study","volume":"5","author":"Baraliakos","year":"2019","journal-title":"RMD Open"},{"key":"ref_195","doi-asserted-by":"crossref","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":"ref_196","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1016\/S0140-6736(18)31946-9","article-title":"Ixekizumab, an Interleukin-17A Antagonist in the Treatment of Ankylosing Spondylitis or Radiographic Axial Spondyloarthritis in Patients Previously Untreated with Biological Disease-Modifying Anti-Rheumatic Drugs (COAST-V): 16 Week Results of a Phase 3 R","volume":"392","author":"Dougados","year":"2018","journal-title":"Lancet"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1136\/annrheumdis-2019-216118","article-title":"Efficacy and Safety of Ixekizumab through 52 Weeks in Two Phase 3, Randomised, Controlled Clinical Trials in Patients with Active Radiographic Axial Spondyloarthritis (COAST-V and COAST-W)","volume":"79","author":"Dougados","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1136\/ard-2022-223296","article-title":"ASAS-EULAR Recommendations for the Management of Axial Spondyloarthritis: 2022 Update","volume":"82","author":"Ramiro","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/bjd.16497","article-title":"Ixekizumab or Secukinumab in Psoriasis: What Difference Does It Make?","volume":"178","author":"Paul","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/rheumatology\/key375","article-title":"Secukinumab Shows Sustained Efficacy and Low Structural Progression in Ankylosing Spondylitis: 4-Year Results from the MEASURE 1 Study","volume":"58","author":"Braun","year":"2019","journal-title":"Rheumatology"},{"key":"ref_201","first-page":"1936","article-title":"Bimekizumab Blocks T Cell-Mediated Osteogenic Differentiation of Periosteal Stem Cells: Coupling Pathological Bone Formation to IL17A and IL-17F Signaling","volume":"69","author":"Shah","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.3389\/fimmu.2020.01894","article-title":"Bimekizumab, a Novel Humanized IgG1 Antibody That Neutralizes Both IL-17A and IL-17F","volume":"11","author":"Adams","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1136\/annrheumdis-2020-216980","article-title":"Dual Neutralisation of Interleukin-17A and Interleukin-17F with Bimekizumab in Patients with Active Ankylosing Spondylitis: Results from a 48-Week Phase IIb, Randomised, Double-Blind, Placebo-Controlled, Dose-Ranging Study","volume":"79","author":"Gensler","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1136\/ard-2022-223595","article-title":"Efficacy and Safety of Bimekizumab in Axial Spondyloarthritis: Results of Two Parallel Phase 3 Randomised Controlled Trials","volume":"82","author":"Deodhar","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_205","doi-asserted-by":"crossref","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":"ref_206","doi-asserted-by":"crossref","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":"ref_207","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/S0140-6736(13)60594-2","article-title":"Efficacy and Safety of Ustekinumab in Patients with Active Psoriatic Arthritis: 1 Year Results of the Phase 3, Multicentre, Double-Blind, Placebo-Controlled PSUMMIT 1 Trial","volume":"382","author":"McInnes","year":"2013","journal-title":"Lancet"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1136\/annrheumdis-2021-221048","article-title":"Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 24-Week Results from the Randomised, Double-Blind, Phase 3 KEEPsAKE 2 Trial","volume":"81","author":"Papp","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1136\/annrheumdis-2021-221019","article-title":"Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 24-Week Results from the Randomised, Double-Blind, Phase 3 KEEPsAKE 1 Trial","volume":"81","author":"Kristensen","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.semarthrit.2018.05.011","article-title":"Effects of Ustekinumab versus Tumor Necrosis Factor Inhibition on Enthesitis: Results from the Enthesial Clearance in Psoriatic Arthritis (ECLIPSA) Study","volume":"48","author":"Araujo","year":"2019","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1002\/art.22758","article-title":"The Concept of a \u201cSynovio-Entheseal Complex\u201d and Its Implications for Understanding Joint Inflammation and Damage in Psoriatic Arthritis and Beyond","volume":"56","author":"McGonagle","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1136\/annrheumdis-2015-209068","article-title":"Efficacy and Safety of Ustekinumab in Psoriatic Arthritis Patients with Peripheral Arthritis and Physician-Reported Spondylitis: Post-Hoc Analyses from Two Phase III, Multicentre, Double-Blind, Placebo-Controlled Studies (PSUMMIT-1\/PSUMMIT-2)","volume":"75","author":"Kavanaugh","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"e715","DOI":"10.1016\/S2665-9913(21)00105-3","article-title":"Efficacy of Guselkumab on Axial Involvement in Patients with Active Psoriatic Arthritis and Sacroiliitis: A Post-Hoc Analysis of the Phase 3 DISCOVER-1 and DISCOVER-2 Studies","volume":"3","author":"Mease","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"585134","DOI":"10.3389\/fimmu.2020.585134","article-title":"Interleukin (IL)-12 and IL-18 Synergize to Promote MAIT Cell IL-17A and IL-17F Production Independently of IL-23 Signaling","volume":"11","author":"Cole","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1002\/art.38638","article-title":"Interleukin-23 Mediates the Intestinal Response to Microbial \u03b2-1,3-Glucan and the Development of Spondyloarthritis Pathology in SKG Mice","volume":"66","author":"Benham","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.3389\/fimmu.2018.01550","article-title":"The Initiation, but Not the Persistence, of Experimental Spondyloarthritis Is Dependent on Interleukin-23 Signaling","volume":"9","author":"Na","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1056\/NEJMra1202117","article-title":"JAKs and STATs in Immunity, Immunodeficiency, and Cancer","volume":"368","author":"Holland","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/pro.3519","article-title":"The Molecular Details of Cytokine Signaling via the JAK\/STAT Pathway","volume":"27","author":"Morris","year":"2018","journal-title":"Protein Sci."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41584-021-00726-8","article-title":"Janus Kinase-Targeting Therapies in Rheumatology: A Mechanisms-Based Approach","volume":"18","author":"Tanaka","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1093\/rheumatology\/keab740","article-title":"A Review of JAK\u2013STAT Signalling in the Pathogenesis of Spondyloarthritis and the Role of JAK Inhibition","volume":"61","author":"McInnes","year":"2022","journal-title":"Rheumatology"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.clim.2010.05.003","article-title":"Analysis of JAK2 and STAT3 Polymorphisms in Patients with Ankylosing Spondylitis in Chinese Han Population","volume":"136","author":"Chen","year":"2010","journal-title":"Clin. Immunol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"363ra149","DOI":"10.1126\/scitranslmed.aag1974","article-title":"Resolving TYK2 Locus Genotype-to-Phenotype Differences in Autoimmunity","volume":"8","author":"Dendrou","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_223","unstructured":"Maeda, Y., Stavre, Z., Huang, T., Manning, C., Shaughn, B., Macoritto, M., Hyland, D., Waegell, W., and Gravallese, E.M. (2018, January 19\u201324). Blockade of the JAK\/STAT Pathway Inhibits Inflammation and Bone Formation in Two Murine Models of Spondyloarthritis. Proceedings of the 2018 ACR\/ARHP Annual Meeting, Chicago, IL, USA."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"15645","DOI":"10.1038\/s41598-018-34026-1","article-title":"Inhibiting Ex-Vivo Th17 Responses in Ankylosing Spondylitis by Targeting Janus Kinases","volume":"8","author":"Hammitzsch","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nrd.2017.201","article-title":"JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases","volume":"16","author":"Schwartz","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_226","doi-asserted-by":"crossref","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":"Deodhar","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1136\/annrheumdis-2020-219601","article-title":"Tofacitinib for the Treatment of Ankylosing Spondylitis: A Phase III, Randomised, Double-Blind, Placebo-Controlled Study","volume":"80","author":"Deodhar","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1016\/S0140-6736(18)32463-2","article-title":"Efficacy and Safety of Filgotinib, a Selective Janus Kinase 1 Inhibitor, in Patients with Active Ankylosing Spondylitis (TORTUGA): Results from a Randomised, Placebo-Controlled, Phase 2 Trial","volume":"392","author":"Baraliakos","year":"2018","journal-title":"Lancet"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/S0140-6736(19)32534-6","article-title":"Efficacy and Safety of Upadacitinib in Patients with Active Ankylosing Spondylitis (SELECT-AXIS 1): A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Phase 2\/3 Trial","volume":"394","author":"Song","year":"2019","journal-title":"Lancet"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1136\/annrheumdis-2022-eular.2534","article-title":"OP0016 efficacy and safety of upadacitinib in patients with active non-radiographic axial spondyloarthritis: A double-blind, randomized, placebo-controlled phase 3 trial","volume":"81","author":"Deodhar","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.celrep.2019.09.035","article-title":"Signal Integration and Transcriptional Regulation of the Inflammatory Response Mediated by the GM-\/M-CSF Signaling Axis in Human Monocytes","volume":"29","author":"Rodriguez","year":"2019","journal-title":"Cell Rep."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s13075-022-02888-6","article-title":"Serum Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Is Increased in Patients with Active Radiographic Axial Spondyloarthritis and Persists despite Anti-TNF Treatment","volume":"24","author":"Papagoras","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s40674-018-0095-1","article-title":"Novel Therapeutic Targets in Axial Spondyloarthritis","volume":"4","author":"Worth","year":"2018","journal-title":"Curr. Treat. Options Rheumatol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/nyas.12059","article-title":"Role of PI3K\/Akt and MTOR Complexes in Th17 Cell Differentiation","volume":"1280","author":"Nagai","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41413-017-0004-5","article-title":"MTOR Signaling in Skeletal Development and Disease","volume":"6","author":"Chen","year":"2018","journal-title":"Bone Res."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.3389\/fimmu.2019.02344","article-title":"MTOR Blockade by Rapamycin in Spondyloarthritis: Impact on Inflammation and New Bone Formation in Vitro and in Vivo","volume":"10","author":"Chen","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"102435","DOI":"10.1016\/j.jaut.2020.102435","article-title":"Selective Targeting of PI3K\u03b4 Suppresses Human IL-17-Producing T Cells and Innate-like Lymphocytes and May Be Therapeutic for IL-17-Mediated Diseases","volume":"111","author":"Chen","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"699987","DOI":"10.3389\/fimmu.2021.699987","article-title":"Paradoxical Augmentation of Experimental Spondyloarthritis by RORC Inhibition in HLA-B27 Transgenic Rats","volume":"12","author":"Mandour","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"151925","DOI":"10.1016\/j.semarthrit.2021.11.002","article-title":"Gut Microbiota Changes in Patients with Spondyloarthritis: A Systematic Review","volume":"52","author":"Wang","year":"2022","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"So, J., and Tam, L.-S. (2020). Gut Microbiome and Its Interaction with Immune System in Spondyloarthritis. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111727"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:06:42Z","timestamp":1760123202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,30]]},"references-count":240,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076463"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076463","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,30]]}}}