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New developments in ankylosing spondylitis-status in 2021.

ABSTRACT: Axial SpA (axSpA) is a common rheumatic disease characterized by inflammation leading to bone formation and functional impairment. TNF-α and IL-17 represent established targets in axSpA. TNF-α and IL-17 inhibitors have demonstrated efficacy in clinical trials and are currently approved biologic DMARDs for all subsets of the disease. Several lines of evidence implicate a role of an IL-23-IL-17 axis in the disease pathogenesis. In this light, and given the success of IL-17 blockade in axSpA, a similar good response to IL-23 was anticipated. Nevertheless, two clinical trials of anti-IL-23 monoclonal antibodies in axSpA have clearly exhibited negative results. This failure has raised theories for a degree of IL-23 independent pathway. The Janus kinase (JAK) pathway is also a potential therapeutic target, since several cytokines, including those involved in the IL-23-IL-17 axis, signal through the JAK family of tyrosine kinases. Further studies and more extended evaluation of response to cytokine inhibition across different tissues will be required to improve our understanding of SpA pathogenesis and determine its optimal management.

SUBMITTER: Klavdianou K

PROVIDER: S-EPMC8709566 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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New developments in ankylosing spondylitis-status in 2021.

Klavdianou Kalliopi K Tsiami Styliani S Baraliakos Xenofon X

Rheumatology (Oxford, England) 20211201 Suppl 6

Axial SpA (axSpA) is a common rheumatic disease characterized by inflammation leading to bone formation and functional impairment. TNF-α and IL-17 represent established targets in axSpA. TNF-α and IL-17 inhibitors have demonstrated efficacy in clinical trials and are currently approved biologic DMARDs for all subsets of the disease. Several lines of evidence implicate a role of an IL-23-IL-17 axis in the disease pathogenesis. In this light, and given the success of IL-17 blockade in axSpA, a sim ...[more]

PMID: 34951921

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Project description:BackgroundThis study aimed to identify the relationship between gait parameters and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS).MethodsThe study group comprised 134 patients with AS and 124 patients were enrolled as controls. All study participants underwent instrumented gait analysis and completed clinical questionnaires. The kinematic parameters of gait were walking speed, step length, cadence, stance phase, single support, double support, phase coordination index (PCI), and gait asymmetry (GA). For each patient, a visual analog scale (VAS; 0-10) score was used to assess back pain, 36-item short form survey (SF-36) questionnaire was administered to evaluate the HRQOL, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was calculated. Using kinematic parameters and questionnaires, statistical analyses were done to investigate significant differences between the groups. Relationship of gait kinematic data and questionnaires of clinical outcome was also evaluated.ResultsAmong the 134 patients with AS, 34 were women and 100 were men. In the control group, 26 were women and 98 were men. The patients with AS and control group patients had significant differences in terms of walking speed, step length, single support, PCI, and GA. However, such differences were not observed in cadence, stance phase, and double support (p > 0.05). In correlation analyses, gait kinematic parameters and clinical outcomes were significantly related with each other. In multiple regression analysis performed to identify predictive factors for clinical outcome, walking speed was found to predict VAS, and walking speed and step length were found to predict the BASDAI and SF-36 scores.ConclusionsPatients with and without AS had significant differences in the gait parameters. Correlation analysis showed significant correlation between the gait kinematic data and clinical outcomes. In particular, walking speed and step length successfully predicted clinical outcomes in patients with AS.

Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

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New developments in ankylosing spondylitis-status in 2021.

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New developments in ankylosing spondylitis-status in 2021.

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