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F1000Research 2018The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing... (Review)
Review
The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease.
Topics: Disease Management; Humans; Spondylitis, Ankylosing; Therapeutics
PubMed: 30345001
DOI: 10.12688/f1000research.14956.1 -
Frontiers in Immunology 2019
Topics: Disease Management; Disease Susceptibility; Humans; Immune System Diseases; Spondylitis, Ankylosing
PubMed: 31214188
DOI: 10.3389/fimmu.2019.01232 -
Frontiers in Immunology 2021
Topics: Adaptive Immunity; Animals; Anti-Inflammatory Agents; Cost of Illness; Humans; Immunity, Innate; Quality of Life; Sacroiliac Joint; Spine; Spondylitis, Ankylosing
PubMed: 35003143
DOI: 10.3389/fimmu.2021.822582 -
Rheumatic Diseases Clinics of North... Aug 2017Ankylosing spondylitis (AS) is a common inflammatory arthritis in which genetic factors are the primary determinants of disease risk and severity. Substantial progress... (Review)
Review
Ankylosing spondylitis (AS) is a common inflammatory arthritis in which genetic factors are the primary determinants of disease risk and severity. Substantial progress has been made in identifying genetic pathways involved in the disease, and in translating those discoveries to drug discovery programs. Recently discovered novel disease pathways include those involved in control of DNA methylation, bacterial sensing, and mucosal immunity. Additional pathways are likely to be identified as a higher proportion of the genetic risk of AS is determined.
Topics: Genetic Pleiotropy; Genetic Predisposition to Disease; HLA-B27 Antigen; Humans; Spondylitis, Ankylosing
PubMed: 28711142
DOI: 10.1016/j.rdc.2017.04.006 -
Nature Reviews. Rheumatology Jul 2021Ankylosing spondylitis (AS) is a chronic inflammatory disorder of unknown aetiology. Unlike other systemic autoimmune diseases, in AS, the innate immune system has a... (Review)
Review
Ankylosing spondylitis (AS) is a chronic inflammatory disorder of unknown aetiology. Unlike other systemic autoimmune diseases, in AS, the innate immune system has a dominant role characterized by aberrant activity of innate and innate-like immune cells, including γδ T cells, group 3 innate lymphoid cells, neutrophils, mucosal-associated invariant T cells and mast cells, at sites predisposed to the disease. The intestine is involved in disease manifestations, as it is at the forefront of the interaction between the mucosal-associated immune cells and the intestinal microbiota. Similarly, biomechanical factors, such as entheseal micro-trauma, might also be involved in the pathogenesis of the articular manifestation of AS, and sentinel immune cells located in the entheses could provide links between local damage, genetic predisposition and the development of chronic inflammation. Although these elements might support the autoinflammatory nature of AS, studies demonstrating the presence of autoantibodies (such as anti-CD74, anti-sclerostin and anti-noggin antibodies) and evidence of activation and clonal expansion of T cell populations support an autoimmune component to the disease. This Review presents the evidence for autoinflammation and the evidence for autoimmunity in AS and, by discussing the pathophysiological factors associated with each, aims to reconcile the two hypotheses.
Topics: Animals; Autoimmune Diseases; Hereditary Autoinflammatory Diseases; Humans; Spondylitis, Ankylosing
PubMed: 34113018
DOI: 10.1038/s41584-021-00625-y -
Lancet (London, England) Jul 2017The term axial spondyloarthritis covers both patients with non-radiographic and radiographic axial spondyloarthritis, which is also termed ankylosing spondylitis. The... (Review)
Review
The term axial spondyloarthritis covers both patients with non-radiographic and radiographic axial spondyloarthritis, which is also termed ankylosing spondylitis. The disease usually starts in the third decade of life with a male to female ratio of two to one for radiographic axial spondyloarthritis and of one to one for non-radiographic axial spondyloarthritis. More than 90% heritabilty has been estimated, the highest genetic association being with HLA-B27. The pathogenic role of HLA-B27 is still not clear although various hypotheses are available. On the basis of evidence from trials the cytokines tumour necrosis factor (TNF)-α and interleukin-17 appear to have a relevant role in pathogenesis. The mechanisms of interaction between inflammation and new bone formation is still not completely understood but clarification will be important for the prevention of long-term structural damage of the bone. The development of new criteria for classification and for screening of patients with axial spondyloarthritis have been crucial for the early indentification and treatment of such patients, with MRI being the most important existing imaging method. Non-steroidal anti-inflammatory drugs and TNF blockers are effective therapies. Blockade of interleukin-17 is a new and relevant treatment option.
Topics: Back Pain; Early Diagnosis; Humans; Inflammation; Magnetic Resonance Imaging; Spondylitis, Ankylosing
PubMed: 28110981
DOI: 10.1016/S0140-6736(16)31591-4 -
Current Allergy and Asthma Reports Jan 2015Ankylosing spondylitis is an insidiously progressive and debilitating form of arthritis involving the axial skeleton. The long delay in diagnosis and insufficient... (Review)
Review
Ankylosing spondylitis is an insidiously progressive and debilitating form of arthritis involving the axial skeleton. The long delay in diagnosis and insufficient response to currently available therapeutics both advocate for a greater understanding of disease pathogenesis. Genome-wide association studies of this highly genetic disease have implicated specific immune pathways, including the interleukin (IL)-17/IL-23 pathway, control of nuclear factor kappa B (NF-κB) activation, amino acid trimming for major histocompatibility complex (MHC) antigen presentation, and other genes controlling CD8 and CD4 T cell subsets. The relevance of these pathways has borne out in animal and human subject studies, in particular, the response to novel therapeutic agents. Genetics and the findings of autoantibodies in ankylosing spondylitis revisit the question of autoimmune vs. autoinflammatory etiology. As environmental partners to genetics, recent attention has focused on the roles of microbiota and biomechanical stress in initiating and perpetuating inflammation. Herein, we review these current developments in the investigation of ankylosing spondylitis pathogenesis.
Topics: Animals; Autoimmune Diseases; CD4-Positive T-Lymphocytes; Genetic Predisposition to Disease; Humans; Interleukin-17; Interleukin-23; Spondylitis, Ankylosing
PubMed: 25447326
DOI: 10.1007/s11882-014-0489-6 -
Archives of Physical Medicine and... Feb 2018To assess the effectiveness of exercise programs on disease activity and function in ankylosing spondylitis (AS) by a systematic review and meta-analysis of randomized... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effectiveness of exercise programs on disease activity and function in ankylosing spondylitis (AS) by a systematic review and meta-analysis of randomized controlled trials (RCTs).
DATA SOURCES
Medline via PubMed and Cochrane Library.
STUDY SELECTION
Reports of RCTs examining the effectiveness of exercise programs for AS published up to May 2017.
DATA EXTRACTION
Outcomes were evolution of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after the completion of exercise programs. Modalities of exercise were compared and the use of biologic therapy was reported.
DATA SYNTHESIS
After screening 190 abstracts, we selected 26 reports for detailed evaluation and finally investigated 8 trials that assessed a home-based exercise program (2/8), swimming (1/8), Pilates training (1/8), or supervised exercises (4/8), for a total of 331 patients with AS. Four trials included patients receiving antitumor necrosis factor therapy. All trials except one showed a decrease in BASDAI and BASFI with exercise. The weighted mean difference was -0.90 (95% confidence interval, -1.52 to -0.27; I=69%; P=.005) for the BASDAI and -0.72 (95% confidence interval, -1.03 to -0.40; I=0%; P<.00001) for the BASFI in favor of exercise programs.
CONCLUSIONS
Despite the small number of patients and the heterogeneity of exercise programs in the RCTs included in this meta-analysis, its results support the potential of exercise programs to improve disease activity and body function in AS.
Topics: Exercise Therapy; Humans; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing
PubMed: 28860095
DOI: 10.1016/j.apmr.2017.07.015 -
Clinical and Experimental Rheumatology 2018Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammatory back pain and several other disease manifestations and comorbidities. The... (Review)
Review
Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammatory back pain and several other disease manifestations and comorbidities. The 2009 ASAS classification criteria differentiate between the classical ankylosing spondylitis or radiographic axSpA and non-radiographic axSpA based on the presence or absence of definite radiographic changes in the sacroiliac joints. Importantly, back pain in patients with axSpA may well have reasons other than axial inflammation or new bone formation. There are several important differential diagnoses such as diffuse idiopathic skeletal hyperostosis and osteitis condensans. This review summarises recent publications concerning the performance of imaging modalities in the field, such as conventional radiography, magnetic resonance imaging, computed tomography and dual energy x-ray absorptiometry including the trabecular bone score.
Topics: Back Pain; Diagnosis, Differential; Diagnostic Imaging; Humans; Predictive Value of Tests; Prognosis; Reproducibility of Results; Rheumatology; Sacroiliac Joint; Severity of Illness Index; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 30296971
DOI: No ID Found -
Frontiers in Immunology 2021The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked... (Review)
Review
The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked to psoriasis and also the arthritis associated with inflammatory bowel disease. The argument supporting the role for IL-23 across the spectrum of SpA comes from 4 sources. First, genome wide associated studies (GWAS) have shown that all the aforementioned disorders exhibit IL-23R pathway SNPs, whereas HLA-B27 is not linked to all of these diseases-hence the IL-23 pathway represents the common genetic denominator. Secondly, experimental animal models have demonstrated a pivotal role for the IL-23/IL-17 axis in SpA related arthropathy that initially manifests as enthesitis, but also synovitis and axial inflammation and also associated aortic root and cutaneous inflammation. Thirdly, the emergent immunology of the human enthesis also supports the presence of IL-23 producing myeloid cells, not just at the enthesis but in other SpA associated sites including skin and gut. Finally, drugs that target the IL-23 pathway show excellent efficacy for skin disease, efficacy for IBD and also in peripheral arthropathy associated with SpA. The apparent failure of IL-23 blockade in the AS which is effectively a spinal polyenthesitis but evidence for efficacy of IL-23 inhibition for peripheral enthesitis in PsA and preliminary suggestions for benefit in axial PsA, raises many questions. Key amongst these is whether spinal inflammation may exhibit entheseal IL-17A production independent of IL-23 but peripheral enthesitis is largely dependent on IL-23 driven IL-17 production. Furthermore, IL-23 blocking strategies in animal models may prevent experimental SpA evolution but not prevent established disease, perhaps pointing towards a role for IL-23 in innate immune disease initiation whereas persistent disease is dependent on memory T-cell responses that drive IL-17A production independently of IL-23, but this needs further study. Furthermore, IL-12/23 posology in inflammatory bowel disease is substantially higher than that used in AS trials which merits consideration. Therefore, the IL-23 pathway is centrally involved in the SpA concept but the nuances and intricacies in axial inflammation that suggest non-response to IL-23 antagonism await formal definition. The absence of comparative immunology between the different skeletal sites renders explanations purely hypothetical at this juncture.
Topics: Animals; Biomarkers; Diagnosis, Differential; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Interleukin-17; Interleukin-23; Molecular Targeted Therapy; Signal Transduction; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 33815371
DOI: 10.3389/fimmu.2021.614255