{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:00:03Z","timestamp":1787508003595,"version":"build-2736575974"},"reference-count":188,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"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>Extensive research into ankylosing spondylitis (AS) has suggested the major role of genetics, immune reactions, and the joint\u2013gut axis in its etiology, although an ultimate consensus does not yet exist. The available evidence indicates that both autoinflammation and T-cell-mediated autoimmune processes are actively involved in the disease process of AS. So far, B cells have received relatively little attention in AS pathogenesis; this is largely due to a lack of conventional disease-defining autoantibodies. However, against prevailing dogma, there is a growing body of evidence suggestive of B cell involvement. This is illustrated by disturbances in circulating B cell populations and the formation of auto-reactive and non-autoreactive antibodies, along with B cell infiltrates within the axial skeleton of AS patients. Furthermore, the depletion of B cells, using rituximab, displayed beneficial results in a subgroup of patients with AS. This review provides an overview of our current knowledge of B cells in AS, and discusses their potential role in its pathogenesis. An overarching picture portrays increased B cell activation in AS, although it is unclear whether B cells directly affect pathogenesis, or are merely bystanders in the disease process.<\/jats:p>","DOI":"10.3390\/ijms222413325","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:28:11Z","timestamp":1639358891000},"page":"13325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7865-6742","authenticated-orcid":false,"given":"Rick","family":"Wilbrink","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"Spoorenberg","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenny M. P. J.","family":"Verstappen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G. M.","family":"Kroese","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1016\/S0140-6736(11)60071-8","article-title":"Spondyloarthritis","volume":"377","author":"Dougados","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(16)31591-4","article-title":"Axial Spondyloarthritis","volume":"390","author":"Sieper","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1136\/annrheumdis-2013-203582","article-title":"Prevalence of Extra-Articular Manifestations in Patients with Ankylosing Spondylitis: A Systematic Review and Meta-Analysis","volume":"74","author":"Stolwijk","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41584-021-00625-y","article-title":"Ankylosing Spondylitis: An Autoimmune or Autoinflammatory Disease?","volume":"17","author":"Mauro","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41584-019-0294-7","article-title":"The IL-23\u2013IL-17 Pathway as a Therapeutic Target in Axial Spondyloarthritis","volume":"15","author":"Sieper","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.3389\/fimmu.2018.02668","article-title":"The Early Phases of Ankylosing Spondylitis: Emerging Insights From Clinical and Basic Science","volume":"9","author":"Watad","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.berh.2018.07.011","article-title":"Born to Run: The Paradox of Biomechanical Force in Spondyloarthritis from an Evolutionary Perspective","volume":"31","author":"Debusschere","year":"2017","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/j.0105-2896.2009.00852.x","article-title":"Genetics and Genomics of Ankylosing Spondylitis","volume":"233","author":"Thomas","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_10","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":"Mediat. Inflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10615","DOI":"10.1111\/jcmm.15680","article-title":"Association of IFN-\u03b3 Polymorphisms with Ankylosing Spondylitis Risk","volume":"24","author":"Liu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fimmu.2018.00422","article-title":"Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity","volume":"9","author":"Smith","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"37573","DOI":"10.1074\/jbc.M205470200","article-title":"Molecular Mimicry of an HLA-B27-Derived Ligand of Arthritis-Linked Subtypes with Chlamydial Proteins","volume":"277","author":"Ramos","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1136\/annrheumdis-2016-210000","article-title":"Dysbiosis and Zonulin Upregulation Alter Gut Epithelial and Vascular Barriers in Patients with Ankylosing Spondylitis","volume":"76","author":"Ciccia","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"vi4","DOI":"10.1093\/rheumatology\/key001","article-title":"Progress in Our Understanding of the Pathogenesis of Ankylosing Spondylitis","volume":"57","author":"Simone","year":"2018","journal-title":"Rheumatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41584-018-0091-8","article-title":"Effects of the IL-23\u2013IL-17 Pathway on Bone in Spondyloarthritis","volume":"14","author":"Gravallese","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1002\/art.22060","article-title":"Immunohistologic Analysis of Zygapophyseal Joints in Patients with Ankylosing Spondylitis","volume":"54","author":"Appel","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.3389\/fimmu.2021.686273","article-title":"CD27-CD38lowCD21low B-Cells Are Increased in Axial Spondyloarthritis","volume":"12","author":"Wilbrink","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Quaden, D.H.F., de Winter, L.M., and Somers, V. (2016). Detection of Novel Diagnostic Antibodies in Ankylosing Spondylitis: An Overview, Elsevier B.V.","DOI":"10.1016\/j.autrev.2016.06.001"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1136\/annrheumdis-2018-213779","article-title":"HLA Class I and II Alleles in Susceptibility to Ankylosing Spondylitis","volume":"78","author":"Reveille","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s12016-016-8538-7","article-title":"The Bach Family of Transcription Factors: A Comprehensive Review","volume":"50","author":"Zhou","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4048","DOI":"10.1038\/emboj.2010.257","article-title":"Bach2 Represses Plasma Cell Gene Regulatory Network in B Cells to Promote Antibody Class Switch","volume":"29","author":"Muto","year":"2010","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.4049\/jimmunol.1801400","article-title":"Bach2 Controls T Follicular Helper Cells by Direct Repression of Bcl-6","volume":"202","author":"Lahmann","year":"2019","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.4049\/jimmunol.1801626","article-title":"Bach2 Negatively Regulates Tfh Cell Differentiation and Is Critical for CD4+ T Cell Memory","volume":"202","author":"Geng","year":"2019","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/gene.2017.11","article-title":"Epigenetic and Gene Expression Analysis of Ankylosing Spondylitis-Associated Loci Implicate Immune Cells and the Gut in the Disease Pathogenesis","volume":"18","author":"Li","year":"2017","journal-title":"Genes Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nri3536","article-title":"T-Bet: A Bridge between Innate and Adaptive Immunity","volume":"13","author":"Lazarevic","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","article-title":"A Novel Transcription Factor, T-Bet, Directs Th1 Lineage Commitment","volume":"100","author":"Szabo","year":"2000","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/ni.1731","article-title":"The Transcription Factor T-Bet Controls Regulatory T Cell Homeostasis and Function during Type 1 Inflammation","volume":"10","author":"Koch","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1073\/pnas.082114899","article-title":"T-Bet Regulates IgG Class Switching and Pathogenic Production","volume":"99","author":"Peng","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/imr.12736","article-title":"T-Bet+ Memory B Cells: Generation, Function, and Fate","volume":"288","author":"Knox","year":"2019","journal-title":"Immunol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/j.celrep.2019.10.087","article-title":"Transcription Factor T-Bet in B Cells Modulates Germinal Center Polarization and Antibody Affinity Maturation in Response to Malaria","volume":"29","author":"Ly","year":"2019","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"653611","DOI":"10.3389\/fimmu.2021.653611","article-title":"Influence of IL10 (Rs1800896) Polymorphism and TNF-\u03b1, IL-10, IL-17A, and IL-17F Serum Levels in Ankylosing Spondylitis","volume":"12","author":"Braga","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nri2711","article-title":"The Regulation of IL-10 Production by Immune Cells","volume":"10","author":"Saraiva","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.immuni.2009.11.009","article-title":"CD19+CD24hiCD38hi B Cells Exhibit Regulatory Capacity in Healthy Individuals but Are Functionally Impaired in Systemic Lupus Erythematosus Patients","volume":"32","author":"Blair","year":"2010","journal-title":"Immunity"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.cell.2019.03.016","article-title":"B Cell Responses: Cell Interaction Dynamics and Decisions","volume":"177","author":"Cyster","year":"2019","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9518137","DOI":"10.1155\/2020\/9518137","article-title":"Peripheral B Cell Subsets in Autoimmune Diseases: Clinical Implications and Effects of B Cell-Targeted Therapies","volume":"2020","author":"Jin","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/BF01330297","article-title":"Stimulation of Whole Blood Cultures in Patients with Ankylosing Spondylitis by a Mitogen Derived FromMycoplasma Arthritidis (MAS) and Other Mitogens","volume":"16","author":"Brand","year":"1997","journal-title":"Rheumatol. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s10067-011-1721-6","article-title":"Inverse Correlation of Programmed Death 1 (PD-1) Expression in T Cells to the Spinal Radiologic Changes in Taiwanese Patients with Ankylosing Spondylitis","volume":"30","author":"Chen","year":"2011","journal-title":"Clin. Rheumatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.3899\/jrheum.070839","article-title":"Intracytoplasmic Cytokine Expression and T Cell Subset Distribution in the Peripheral Blood of Patients with Ankylosing Spondylitis","volume":"35","author":"Alesza","year":"2008","journal-title":"J. Rheumatol."},{"key":"ref_44","first-page":"4578","article-title":"High Frequency of Circulating Follicular Helper T Cells Is Correlated with B Cell Subtypes in Patients with Ankylosing Spondylitis","volume":"15","author":"Long","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_45","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_46","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_47","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_48","doi-asserted-by":"crossref","unstructured":"Bautista-Caro, M.B., Arroyo-Villa, I., Castillo-Gallego, C., de Miguel, E., Peiteado, D., Plasencia-Rodr\u00edguez, C., Villalba, A., Sanchez-Mateos, P., Puig-Kr\u00f6ger, A., and Mart\u00edn-Mola, E. (2014). Decreased Frequencies of Circulating Follicular Helper T Cell Counterparts and Plasmablasts in Ankylosing Spondylitis Patients Na\u00efve for TNF Blockers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107086"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.lfs.2013.09.003","article-title":"Peripheral B-Cell Activation and Exhaustion Markers in Patients with Ankylosing Spondylitis","volume":"93","author":"Niu","year":"2013","journal-title":"Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.3389\/fimmu.2019.02458","article-title":"Challenges and Opportunities for Consistent Classification of Human B Cell and Plasma Cell Populations","volume":"10","author":"Sanz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3389\/fimmu.2012.00372","article-title":"Multiple Regulatory Mechanisms Control B-1 B Cell Activation","volume":"3","author":"Sindhava","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/art.34364","article-title":"Increased Numbers of CD5+ B Lymphocytes with a Regulatory Phenotype in Spondylarthritis","volume":"64","author":"Cantaert","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_53","first-page":"2527","article-title":"Effect of Abnormal Activated B Cells in Patients with Ankylosing Spondylitis and Its Molecular Mechanism","volume":"22","author":"Ge","year":"2018","journal-title":"Eur. Rev. Med Pharmacol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.5114\/reum.2015.50551","article-title":"Cytokine Profiles in Axial Spondyloarthritis","volume":"53","author":"Madej","year":"2015","journal-title":"Reumatologia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1399-0039.1997.tb02703.x","article-title":"Role of the Human CD38 Molecule in B Cell Activation and Proliferation","volume":"49","author":"Funaro","year":"1997","journal-title":"Tissue Antigens"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7766","DOI":"10.1074\/jbc.M105902200","article-title":"Distinct Role of CD80 and CD86 in the Regulation of the Activation of B Cell and B Cell Lymphoma","volume":"277","author":"Suvas","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/eji.1830260332","article-title":"Activated B Cells Express Functional Fas Ligand","volume":"26","author":"Hahne","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3389\/fimmu.2012.00207","article-title":"The Fas\/CD95 Receptor Regulates the Death of Autoreactive B Cells and the Selection of Antigen-Specific B Cells","volume":"3","author":"Koncz","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fimmu.2012.00078","article-title":"Origin and Function of Circulating Plasmablasts during Acute Viral Infections","volume":"3","author":"Fink","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3109\/14397595.2014.902149","article-title":"Increased Frequency of Circulating Follicular Helper T Cells in Patients with Ankylosing Spondylitis","volume":"25","author":"Wu","year":"2015","journal-title":"Mod. Rheumatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/sji.12339","article-title":"CD21 \u2212\/Low B Cells: A Snapshot of a Unique B Cell Subset in Health and Disease","volume":"82","author":"Thorarinsdottir","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.clim.2004.05.010","article-title":"A New CD21low B Cell Population in the Peripheral Blood of Patients with SLE","volume":"113","author":"Wehr","year":"2004","journal-title":"Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/art.37828","article-title":"Expansion of Autoreactive Unresponsive CD21-\/Low B Cells in Sj\u00f6gren\u2019s Syndrome-Associated Lymphoproliferation","volume":"65","author":"Saadoun","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.1182\/blood-2009-09-243071","article-title":"Complement Receptor 2\/CD21- Human Naive B Cells Contain Mostly Autoreactive Unresponsive Clones","volume":"115","author":"Isnardi","year":"2010","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/cei.12795","article-title":"CD21\u2013\/Low B Cells in Human Blood Are Memory Cells","volume":"185","author":"Thorarinsdottir","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1038\/s41467-018-03750-7","article-title":"IL-21 Drives Expansion and Plasma Cell Differentiation of Autoreactive CD11chiT-Bet+ B Cells in SLE","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.immuni.2019.04.004","article-title":"T-Bet Transcription Factor Promotes Antibody Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN\u03b3 on B Cells HHS Public Access","volume":"50","author":"Stone","year":"2019","journal-title":"Immunity"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3389\/fimmu.2020.00032","article-title":"CD11c+ B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors","volume":"11","author":"Golinski","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_69","first-page":"158","article-title":"Increased Frequency of Leukocyte-Reactive Antinuclear Antibody in Patients with Ankylosing Spondylitis","volume":"4","author":"Vasey","year":"1977","journal-title":"J. Rheumatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1136\/ard.38.6.526","article-title":"Antinuclear Antibodies in Ankylosing Spondylitis, Psoriatic Arthritis, and Psoriasis","volume":"38","author":"Rosenberg","year":"1979","journal-title":"Ann. Rheum. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1046\/j.1365-2249.1999.01008.x","article-title":"Anti-Lactoferrin Antibodies and Other Types of Anti-Neutrophil Cytoplasmic Antibodies (ANCA) in Reactive Arthritis and Ankylosing Spondylitis","volume":"117","author":"Locht","year":"1999","journal-title":"Clin. Exp. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.3899\/jrheum.100269","article-title":"PANCA, ASCA, and OmpC Antibodies in Patients with Ankylosing Spondylitis without Inflammatory Bowel Disease","volume":"37","author":"Ratnawati","year":"2010","journal-title":"J. Rheumatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fimmu.2019.00384","article-title":"Prefoldin 5 and Anti-Prefoldin 5 Antibodies as Biomarkers for Uveitis in Ankylosing Spondylitis","volume":"10","author":"Kwon","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/art.1780250403","article-title":"Antibodies to and Elevations of Beta 2 Microglobulin in the Serum of Ankylosing Spondylitis Patients","volume":"25","author":"Curry","year":"1982","journal-title":"Arthritis Rheum."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1136\/annrheumdis-2012-202208","article-title":"Autoantibodies against CD74 in Spondyloarthritis","volume":"73","author":"Baerlecken","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_76","first-page":"1127","article-title":"IgA Antibodies against CD74 Are Associated with Structural Damage in the Axial Skeleton in Patients with Axial Spondyloarthritis","volume":"38","author":"Witte","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3389\/fimmu.2019.00574","article-title":"Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence","volume":"10","author":"Ziade","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13075-018-1535-x","article-title":"Anti-CD74 Antibodies Have No Diagnostic Value in Early Axial Spondyloarthritis: Data from the Spondyloarthritis Caught Early (SPACE) Cohort","volume":"20","author":"Baerlecken","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/art.40777","article-title":"Sensitivity and Specificity of Autoantibodies Against CD74 in Nonradiographic Axial Spondyloarthritis","volume":"71","author":"Riechers","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e23433","DOI":"10.1097\/MD.0000000000023433","article-title":"CD74 Auto-Antibodies Display Little Clinical Value in Chinese Han Population with Axial Spondyloarthritis","volume":"99","author":"Hu","year":"2020","journal-title":"Medicine"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1093\/rheumatology\/keaa882","article-title":"Anti-CD74 IgA Autoantibodies in Radiographic Axial Spondyloarthritis: A Longitudinal Swedish Study","volume":"60","author":"Do","year":"2021","journal-title":"Rheumatology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1136\/ard.54.8.631","article-title":"IgAl and IgA2 Subclass Antibodies against Klebsiella Pneumoniae in the Sera of Patients with Peripheral and Axial Types of Ankylosing Spondylitis","volume":"54","author":"Lehtinen","year":"1995","journal-title":"Ann. Rheum. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1136\/ard.62.5.455","article-title":"Anti-Saccharomyces Cerevisiae IgA Antibodies Are Raised in Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy","volume":"62","author":"Hoffman","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"R166","DOI":"10.1186\/ar4350","article-title":"Elevated Serum Anti-Flagellin Antibodies Implicate Subclinical Bowel Inflammation in Ankylosing Spondylitis: An Observational Study","volume":"15","author":"Wallis","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_86","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_87","first-page":"55","article-title":"Serum Heat-Shock Protein-65 Antibody Levels Are Elevated but Not Associated with Disease Activity in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis","volume":"10","author":"Ulusoy","year":"2018","journal-title":"Open Access Rheumatol. Res. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3109\/03009748309098543","article-title":"Iga Antibodies to Klebsiella Pneumoniae in Ankylosing Spondylitis","volume":"12","author":"Trull","year":"2009","journal-title":"Scand. J. Rheumatol."},{"key":"ref_89","first-page":"743","article-title":"Antibodies to Klebsiella Pneumoniae in Dutch Patients with Ankylosing Spondylitis and Acute Anterior Uveitis and to Proteus Mirabilis in Rheumatoid Arthritis","volume":"25","author":"Fielder","year":"1998","journal-title":"J. Rheumatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3899\/jrheum.170833","article-title":"Sclerostin and Antisclerostin Antibody Serum Levels Predict the Presence of Axial Spondyloarthritis in Patients with Inflammatory Bowel Disease","volume":"45","author":"Luchetti","year":"2018","journal-title":"J. Rheumatol."},{"key":"ref_91","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_92","doi-asserted-by":"crossref","first-page":"M9.00384","DOI":"10.1074\/mcp.M9.00384","article-title":"Detection of Multiple Autoantibodies in Patients with Ankylosing Spondylitis Using Nucleic Acid Programmable Protein Arrays","volume":"11","author":"Wright","year":"2012","journal-title":"Mol. Cell. Proteom."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Hu, Q., Sun, Y., Li, Y., Shi, H., Teng, J., Liu, H., Cheng, X., Ye, J., Su, Y., and Yin, Y. (2018). Anti-SIRT1 Autoantibody Is Elevated in Ankylosing Spondylitis: A Potential Disease Biomarker. BMC Immunol., 19.","DOI":"10.1186\/s12865-018-0280-x"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1002\/art.38763","article-title":"Role of Protein Phosphatase Magnesium-Dependent 1a and Anti-Protein Phosphatase Magnesium-Dependent 1A Autoantibodies in Ankylosing Spondylitis","volume":"66","author":"Kim","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lee, J.-S., Lee, E.-J., Lee, J.-H., Hong, S.-C., Lee, C.-K., Yoo, B., Oh, J.-S., Lee, S.-H., Kim, T.-J., and Lee, S.-H. (2020). Autoantibodies against Protein Phosphatase Magnesium-Dependent 1A as a Biomarker for Predicting Radiographic Progression in Ankylosing Spondylitis Treated with Anti-Tumor Necrosis Factor Agents. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123968"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00223-017-0291-2","article-title":"Autoantibodies to Osteoprotegerin Are Associated with Low Hip Bone Mineral Density and History of Fractures in Axial Spondyloarthritis: A Cross-Sectional Observational Study","volume":"101","author":"Hauser","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1093\/jnen\/nly079","article-title":"Acute Sarcomeric M-Line Disease Associated with ATP Synthase Subunit a Autoantibodies in Ankylosing Spondylitis","volume":"77","author":"Guglielmi","year":"2018","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3109\/03009749709065703","article-title":"Serum IgA1 and IgA2 Subclass Antibodies against Collagens in Patients with Ankylosing Spondylitis","volume":"26","author":"Tani","year":"1997","journal-title":"Scand. J. Rheumatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/1756-185X.13113","article-title":"Strongly Positive Anti-CCP Antibodies in Patients with Sacroiliitis or Reactive Arthritis Post-E. Coli Infection: A Mini Case-Series Based Review","volume":"21","author":"Wright","year":"2018","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4598","DOI":"10.1093\/rheumatology\/keab050","article-title":"Predictive Value of Anti-CarP and Anti-PAD3 Antibodies Alone or in Combination with RF and ACPA for the Severity of Rheumatoid Arthritis","volume":"60","author":"Lamacchia","year":"2021","journal-title":"Rheumatology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1080\/03009742.2020.1798500","article-title":"Antibodies against Carbamylated Proteins: Prevalence and Associated Disease Characteristics in Belgian Patients with Rheumatoid Arthritis or Other Rheumatic Diseases","volume":"50","author":"Sidiras","year":"2021","journal-title":"Scand. J. Rheumatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1002\/art.41427","article-title":"Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts","volume":"72","author":"Quaden","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_103","first-page":"401","article-title":"Anti-Nuclear Antibodies, Acti-DNA and C4 Complement Evolution in Rheumatiod Arthritis and Ankylosing Spondylitis Treated with TNF-\u03b1 Blockers","volume":"26","author":"Barnetche","year":"2008","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_104","first-page":"661","article-title":"The Formation of Autoantibodies and Antibodies to TNF-\u03b1 Blocking Agents in Relation to Clinical Response in Patients with Ankylosing Spondylitis","volume":"28","author":"Arends","year":"2010","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11926-015-0500-9","article-title":"Antinuclear Antibody (ANA) Testing in Patients Treated with Biological DMARDs: Is It Useful?","volume":"17","year":"2015","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"27764","DOI":"10.1074\/jbc.M113.476358","article-title":"Prefoldin Plays a Role as a Clearance Factor in Preventing Proteasome Inhibitor-Induced Protein Aggregation","volume":"288","author":"Abe","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/340443a0","article-title":"Association of Class I Major Histocompatibility Heavy and Light Chains Induced by Viral Peptides","volume":"340","author":"Townsend","year":"1989","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/348600a0","article-title":"Intracellular Transport of Class II MHC Molecules Directed by Invariant Chain","volume":"348","author":"Lotteau","year":"1990","journal-title":"Nature"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.3389\/fimmu.2020.01273","article-title":"Role of MIF Cytokine\/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair","volume":"11","author":"Farr","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nri1200","article-title":"Macrophage Migration Inhibitory Factor: A Regulator of Innate Immunity","volume":"3","author":"Calandra","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cyto.2014.11.015","article-title":"Macrophage Migration Inhibitory Factor Is Essential for Osteoclastogenic Mechanisms in Vitro and in Vivo Mouse Model of Arthritis","volume":"72","author":"Gu","year":"2015","journal-title":"Cytokine"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.bone.2009.06.028","article-title":"Macrophage Migration Inhibitory Factor Inhibits Osteoclastogenesis","volume":"45","author":"Jacquin","year":"2009","journal-title":"Bone"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1359\/jbmr.060310","article-title":"Transgenic Mice Overexpressing Macrophage Migration Inhibitory Factor (MIF) Exhibit High-Turnover Osteoporosis","volume":"21","author":"Onodera","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"ref_114","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_115","doi-asserted-by":"crossref","first-page":"eabg1210","DOI":"10.1126\/scitranslmed.abg1210","article-title":"Macrophage Migration Inhibitory Factor Drives Pathology in a Mouse Model of Spondyloarthritis and Is Associated with Human Disease","volume":"13","author":"Nakamura","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"27203","DOI":"10.1074\/jbc.M104684200","article-title":"Invariant Chain Induces B Cell Maturation by Activating a TAFII105-NF-\u039aB-Dependent Transcription Program","volume":"276","author":"Matza","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1182\/blood-2005-11-4334","article-title":"Cell-Surface CD74 Initiates a Signaling Cascade Leading to Cell Proliferation and Survival","volume":"107","author":"Starlets","year":"2006","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1084\/jem.20030286","article-title":"MIF Signal Transduction Initiated by Binding to CD74","volume":"197","author":"Leng","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3109\/s10165-009-0230-9","article-title":"Evaluation of Inflammation and Oxidative Stress in Ankylosing Spondylitis: A Role for Macrophage Migration Inhibitory Factor","volume":"20","author":"Kozaci","year":"2014","journal-title":"Mod. Rheumatol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/rheumatology\/keaa292","article-title":"Diagnostic Value of Anti-CD74 Antibodies in Early and Late Axial Spondyloarthritis and Its Relationship to Disease Activity","volume":"60","author":"Abdelaziz","year":"2021","journal-title":"Rheumatology"},{"key":"ref_121","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_122","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00223-015-0023-4","article-title":"Characterisation of Osteoprotegerin Autoantibodies in Coeliac Disease","volume":"97","author":"Real","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar2165","article-title":"Biology of RANK, RANKL, and Osteoprotegerin","volume":"9","author":"Boyce","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nri2062","article-title":"Osteoimmunology: Shared Mechanisms and Crosstalk between the Immune and Bone Systems","volume":"7","author":"Takayanagi","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/art.39489","article-title":"Production of RANKL by Memory B Cells: A Link Between B Cells and Bone Erosion in Rheumatoid Arthritis","volume":"68","author":"Meednu","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.bone.2008.12.028","article-title":"Prevalence and Risk Factors of Osteoporosis and Vertebral Fractures in Patients with Ankylosing Spondylitis","volume":"44","author":"Ghozlani","year":"2009","journal-title":"Bone"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"119041","DOI":"10.1016\/j.lfs.2021.119041","article-title":"SIRT1, a Promising Regulator of Bone Homeostasis","volume":"269","author":"Chen","year":"2021","journal-title":"Life Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4514","DOI":"10.1210\/en.2011-1128","article-title":"Sirt1 Is a Regulator of Bone Mass and a Repressor of Sost Encoding for Sclerostin, a Bone Formation Inhibitor","volume":"152","author":"Artsi","year":"2011","journal-title":"Endocrinology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bone.2016.10.007","article-title":"Role and Mechanism of Action of Sclerostin in Bone","volume":"96","author":"Sato","year":"2017","journal-title":"Bone"},{"key":"ref_130","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_131","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00223-019-00542-z","article-title":"Serum Sclerostin and Bone Morphogenetic Protein-2 Levels in Patients with Ankylosing Spondylitis: A Meta-Analysis","volume":"105","author":"Yang","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_132","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 Rheumatol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1172\/JCI23738","article-title":"Modulation of Bone Morphogenetic Protein Signaling Inhibits the Onset and Progression of Ankylosing Enthesitis","volume":"115","author":"Lories","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/jbmr.1608","article-title":"Absence of Sclerostin Adversely Affects B-Cell Survival","volume":"27","author":"Cain","year":"2012","journal-title":"J. Bone Miner. Res.  Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11914-020-00563-w","article-title":"The Effects of Sclerostin on the Immune System","volume":"18","author":"Donham","year":"2020","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/rheumatology\/33.7.644","article-title":"Intestinal Permeability in Patients with Ankylosing Spondylitis and Their Healthy Relatives","volume":"33","year":"1994","journal-title":"Br. J. Rheumatol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1136\/annrheumdis-2012-202135","article-title":"Microscopic Gut Inflammation in Axial Spondyloarthritis: A Multiparametric Predictive Model","volume":"72","author":"Jacques","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/rheumatology\/XXVII.suppl_2.95","article-title":"Ileocolonoscopic Findings in Seronegative Spondylarthropathies","volume":"27","author":"Mielants","year":"1988","journal-title":"Br. J. Rheumatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1136\/ard.51.6.790","article-title":"Increased Levels of Serum IgA as IgA1 Monomers in Ankylosing Spondylitis","volume":"51","author":"Hocini","year":"1992","journal-title":"Ann. Rheum. Dis."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1136\/ard.44.11.766","article-title":"IgA Serum Levels and Disease Activity in Ankylosing Spondylitis: A Prospective Study","volume":"44","author":"Franssen","year":"1985","journal-title":"Ann. Rheum. Dis."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Yang, L., Wang, L., Wang, X., Xian, C.J., and Lu, H. (2016). A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122126"},{"key":"ref_142","first-page":"778","article-title":"Low Levels of Heat Shock Proteins-60 and -65 Autoantibodies in Sj\u00f6gren\u2019s Syndrome","volume":"7","author":"Shovman","year":"2005","journal-title":"Isr. Med. Assoc. J. IMAJ"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fimmu.2015.00192","article-title":"Citrullination and Carbamylation in the Pathophysiology of Rheumatoid Arthritis","volume":"6","author":"Pruijn","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jbspin.2012.10.002","article-title":"The Relationship between Peripheral Arthritis and Anti-Cyclic Citrullinated Peptide Antibodies in Ankylosing Spondylitis","volume":"80","author":"Kim","year":"2013","journal-title":"Jt. Bone Spine"},{"key":"ref_145","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_146","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.jcma.2012.05.006","article-title":"Association of Serum Interleukin-17 and Interleukin-23 Levels with Disease Activity in Chinese Patients with Ankylosing Spondylitis","volume":"75","author":"Chen","year":"2012","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10067-010-1647-4","article-title":"Increased Serum IL-17 and IL-23 in the Patient with Ankylosing Spondylitis","volume":"30","author":"Mei","year":"2010","journal-title":"Clin. Rheumatol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s00296-009-0883-x","article-title":"Expression of IL-23 and IL-17 and Effect of IL-23 on IL-17 Production in Ankylosing Spondylitis","volume":"29","author":"Wang","year":"2009","journal-title":"Rheumatol. Int."},{"key":"ref_149","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_150","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_151","first-page":"3472","article-title":"Targeting the Interleukin-23\/Interleukin-17 Inflammatory Pathway: Successes and Failures in the Treatment of Axial Spondyloarthritis","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.3389\/fimmu.2020.623874","article-title":"IL-23 Inhibition in Ankylosing Spondylitis: Where Did It Go Wrong?","volume":"11","author":"Baeten","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri3707","article-title":"The IL-23-IL-17 Immune Axis: From Mechanisms to Therapeutic Testing","volume":"14","author":"Gaffen","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_154","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_155","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 \u2212 CD8 \u2212 Entheseal Resident T Cells","volume":"18","author":"Sherlock","year":"2012","journal-title":"Nat. Med."},{"key":"ref_156","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_157","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.immuni.2015.09.003","article-title":"Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability","volume":"43","author":"Lee","year":"2015","journal-title":"Immunity"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1002\/art.24568","article-title":"S Frequency and Phenotype of Peripheral Blood Th17 Cells in Ankylosing Spondylitis and Rheumatoid Arthritis","volume":"60","author":"Shen","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1159\/000329527","article-title":"IL-17A and IL-17F Expression in B Lymphocytes","volume":"157","author":"Halwani","year":"2012","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Schlegel, P.M., Steiert, I., K\u00f6tter, I., and M\u00fcller, C.A. (2013). B Cells Contribute to Heterogeneity of IL-17 Producing Cells in Rheumatoid Arthritis and Healthy Controls. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082580"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ni1552","article-title":"Interleukin 17\u2013Producing T Helper Cells and Interleukin 17 Orchestrate Autoreactive Germinal Center Development in Autoimmune BXD2 Mice","volume":"9","author":"Hsu","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Halwani, R., Al-Kufaidy, R., Vazquez-Tello, A., Pureza, M.A., BaHammam, A.S., Al-Jahdali, H., Alnassar, S.A., Hamid, Q., and Al-Muhsen, S. (2014). IL-17 Enhances Chemotaxis of Primary Human B Cells during Asthma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114604"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.4049\/jimmunol.1502641","article-title":"IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity","volume":"197","author":"Subbarayal","year":"2016","journal-title":"J. Immunol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nri3700","article-title":"Ectopic Lymphoid-like Structures in Infection, Cancer and Autoimmunity","volume":"14","author":"Pitzalis","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrd4296","article-title":"Interleukin-21: A Double-Edged Sword with Therapeutic Potential","volume":"13","author":"Spolski","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s00296-010-1655-3","article-title":"Increased Plasma Levels of IL-21 and IL-23 in Spondyloarthritis Are Not Associated with Clinical and MRI Findings","volume":"32","author":"Andersen","year":"2010","journal-title":"Rheumatol. Int."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.3899\/jrheum.130125","article-title":"Higher Frequency of Peripheral Blood Interleukin 21 Positive Follicular Helper T Cells in Patients with Ankylosing Spondylitis","volume":"40","author":"Xiao","year":"2013","journal-title":"J. Rheumatol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.4049\/jimmunol.2000206","article-title":"CD11c + T-Bet + B Cells Require IL-21 and IFN-\u03b3 from Type 1 T Follicular Helper Cells and Intrinsic Bcl-6 Expression but Develop Normally in the Absence of T-Bet","volume":"205","author":"Levack","year":"2020","journal-title":"J. Immunol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e20200288","DOI":"10.1084\/jem.20200288","article-title":"Transmembrane TNF Drives Osteoproliferative Joint Inflammation Reminiscent of Human Spondyloarthritis","volume":"217","author":"Kaaij","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_170","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\u2014Cellularity Correlates with the Degree of Enhancement Detected by Magnetic Resonance Imaging","volume":"59","author":"Bollow","year":"2000","journal-title":"Ann. Rheum. Dis."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/rheumatology\/kep174","article-title":"Hip Involvement in Ankylosing Spondylitis: Epidemiology and Risk Factors Associated with Hip Replacement Surgery","volume":"49","author":"Font","year":"2010","journal-title":"Rheumatology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"316421","DOI":"10.1155\/2015\/316421","article-title":"Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement","volume":"2015","author":"Feng","year":"2015","journal-title":"Int. J. Rheumatol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/ar297","article-title":"B Lymphocyte Involvement in Ankylosing Spondylitis: The Heavy Chain Variable Segment Gene Repertoire of B Lymphocytes from Germinal Center-like Foci in the Synovial Membrane Indicates Antigen Selection","volume":"3","author":"Voswinkel","year":"2001","journal-title":"Arthritis Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1046\/j.1365-2249.1996.d01-806.x","article-title":"Evidence for a Selected Humoral Immune Response Encoded by VH4 Family Genes in the Synovial Membrane of a Patient with Rheumatoid Arthritis (RA)","volume":"106","author":"VOSWINKEL","year":"1996","journal-title":"Clin. Exp. Immunol."},{"key":"ref_175","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_176","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1136\/ard.41.6.579","article-title":"Histopathology of the Synovial Membrane of Peripheral Joints in Ankylosing Spondylitis","volume":"41","author":"Revell","year":"1982","journal-title":"Ann. Rheum. Dis."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/1529-0131(199801)41:1<180::AID-ART24>3.0.CO;2-V","article-title":"Immunohistologic Analysis of Peripheral Joint Disease in Ankylosing Spondylitis","volume":"41","author":"Cunnane","year":"1998","journal-title":"Arthritis Rheumatol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1136\/ard.2003.018549","article-title":"Histological Evidence That Infliximab Treatment Leads to Downregulation of Inflammation and Tissue Remodelling of the Synovial Membrane in Spondyloarthropathy","volume":"64","author":"Kruithof","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/s41573-020-00092-2","article-title":"B Cell Depletion Therapies in Autoimmune Disease: Advances and Mechanistic Insights","volume":"20","author":"Lee","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1093\/rheumatology\/ken362","article-title":"The Use of Rituximab to Treat a Patient with Ankylosing Spondylitis and Hepatitis, B","volume":"47","year":"2008","journal-title":"Rheumatology"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1136\/ard.2008.107102","article-title":"Rituximab in the Spondyloarthropathies: Data of Eight Patients Followed up in the French Autoimmunity and Rituximab (AIR) Registry","volume":"69","author":"Nocturne","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"143","DOI":"10.12659\/AJCR.900563","article-title":"Rituximab Can Induce Remission in a Patient with Ankylosing Spondylitis Who Failed Anti-TNF-\u03b1 Agent","volume":"18","author":"AlDhaheri","year":"2017","journal-title":"Am. J. Case Rep."},{"key":"ref_183","first-page":"792526","article-title":"The Efficacy and Safety of Rituximab in a Patient with Rheumatoid Spondylitis","volume":"2013","author":"Kobak","year":"2013","journal-title":"Case Rep. Rheumatol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1007\/s10067-012-2002-8","article-title":"Rituximab in a Patient with Ankylosing Spondylitis with Demyelinating Disease: A Case Report and Review of the Literature","volume":"31","author":"Omair","year":"2012","journal-title":"Clin. Rheumatol."},{"key":"ref_185","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_186","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/art.23266","article-title":"Spondylarthritis in the Absence of B Lymphocytes","volume":"58","author":"Baeten","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_187","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_188","first-page":"CD005468","article-title":"TNF-Alpha Inhibitors for Ankylosing Spondylitis","volume":"4","author":"Maxwell","year":"2015","journal-title":"Cochrane Database Syst. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13325\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:45:31Z","timestamp":1760168731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,11]]},"references-count":188,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413325"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413325","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,11]]}}}