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.
Project description:IntroductionAnkylosing spondylitis (AS) is a universal chronic inflammatory rheumatic disease which predominantly results in chronic back pain and stiffness. However, some patients suffering from AS do not react well to pharmacological interventions. Exercise intervention has been employed for the treatment of AS and works as a complementary part of the management of AS. However, the effect of different types of exercise interventions remains unclear. The purpose of this study is to determine the relative efficacy of different types of exercise interventions for individuals with AS using a Bayesian network meta-analysis.Methods and analysisWe will conduct a systematic literature review of randomised controlled trials that compare different types of exercise interventions for individuals with AS. PubMed, EMBASE and the Cochrane Library will be searched up to February 2019. The primary outcomes are functional capacity, pain and disease activity. The risk of bias for individual studies will be evaluated according to the Cochrane Handbook. A Bayesian network meta-analysis will be performed to compare the efficacy of different types of exercise interventions. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval and patient consent are not required as this study is a meta-analysis based on published studies. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication.Prospero registration numberCRD42019123099.
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.
Project description:Whole blood RNA-sequencing data from 5 AS patients who met 1984 AS criteria and 3 healthy human were obtained to gain insight into the potential mechanism of ankylosing spondylitis.
Project description:Ankylosing spondylitis (AS) is a chronic inflammatory disease with prominent involvement of the spine and sacroiliac joints which frequently leads to significant spine deformity and disability. The development of effective therapies for AS, particularly with anti-tumor necrosis factor agents, has resulted in improved symptoms and functions for many patients, and clinical research increasingly suggests that effective therapy can also prevent destruction in the spine and other structures. Recent focus of disease classification in AS has emphasized that many individuals with features of inflammatory back pain but no visible changes on plain x-rays have active inflammatory disease when imaged with magnetic resonance imaging (MRI). Recent studies indicate that individuals with "non-radiographic" spondylitis can also respond to anti-inflammatory therapies. Several new agents are also showing promise for treatment of AS. These developments represent a significant advance in the management of this debilitating condition.
Project description:BackgroundPreference-based measures of health-related quality of life (HRQoL), such as the EQ-5D or the SF-6D, are essential for health economic evaluation. However, they are rarely included in clinical trials of ankylosing spondylitis (AS). This study aims to develop mapping algorithms to predict EQ-5D-3L and EQ-5D-5L health utility scores from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI).MethodsPatients with AS were recruited from the largest tertiary hospital in Shandong province, China, between December 2019 and October 2020. Patients were selected by convenience sampling method according to the following criteria: (1) diagnosed with AS according to the New York criteria; (2) aged 18 years and above; and (3) without mental disorders; (4) able to understand the questionnaires; (5) without serious complications. There were 243 patients who completed the face-to-face questionnaire survey, and 5 cases with missing values in key variables were excluded. Ordinary least squares, censored least absolute deviations, Tobit, adjusted limited dependent variable mixture model and beta-mixture model (BM) in the direct approach and ordered logit and multinomial logit (Mlogit) model in the response approach were used to develop mapping algorithms. Mean absolute error, root mean square error, Spearman's correlation coefficient and concordance correlation coefficient were used to access predictive performance.ResultsThe 238 patients with AS had a mean age of 35.19 (SD = 9.59) years, and the majority (74.47%) were male. The observed EQ-5D-3L and EQ-5D-5L health utility values were 0.88 (SD = 0.12) and 0.74 (SD = 0.27), respectively. The EQ-5D-5L had higher conceptual overlap with the BASDAI and BASFI than the EQ-5D-3L did. The Mlogit was the best-performing model for the EQ-5D-3L, and the BM showed better performance in predicting EQ-5D-5L than other direct and indirect mapping models did.ConclusionThis study demonstrates that the EQ-5D-5L, rather than EQ-5D-3L, should be selected as the target outcome measure of HRQoL in patients with AS in China, and the BM mapping algorithm could be used to predict EQ-5D-5L values from BASDAI and BASFI for health economic evaluation.
Project description:Cancer is a multifactorial disease, and imbalances of the immune response and sex-associated features are considered risk factors for certain types of cancer. The present study aimed to assess whether ankylosing spondylitis (AS), an immune disorder that predominantly affects young adult men, is associated with an increased risk of cancer. Using the Taiwan National Health Insurance Research Database, a cohort of patients diagnosed with AS between 2000 and 2008 who had no history of cancer prior to enrollment was established (n=5,452). Age- and sex-matched patients without AS served as controls (n=21,808). The results revealed that the overall incidence of cancer was elevated in patients with AS [standardized incidence ratio (SIR), 1.15; 95% confidence interval (CI), 1.03-1.27]. AS carried an increased risk of hematological malignancy in both sexes, colon cancer in females and bone and prostate cancer in males. Young patients with AS (≤35 years) and patients with a Charlson comorbidity index (CCI) ≥2 experienced a higher incidence of cancer (males, SIR 1.92, and 95% CI 1.04-3.26; females, SIR 2.00 and 95% CI 1.46-5.50). The cancer risk was increased during the first 3 years following the diagnosis of AS (SIR 1.49, 95% CI 1.29-1.71), and overall cancer-free survival was significantly decreased in patients with AS patients of both sexes (P<0.0001). Therefore, AS was found to be associated with an increased risk of cancer. All AS patients must be screened for hematological malignancies, for prostate and bone cancer in males, and for colon cancer in females, particularly younger patients with a CCI ≥2.
Project description:Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown etiology, though it is considered an autoimmune disease. HLA-B27 is the risk factor most often associated with AS, and although the mechanism of involvement is unclear, the subtypes and other features of the relationship between HLA-B27 and AS have been studied for years. Additionally, the key role of IL-17 and Th17 cells in autoimmunity and inflammation suggests that the latter and the cytokines involved in their generation could play a role in the pathogenesis of this disease. Recent studies have described the sources of IL-17 and IL-23, as well as the characterization of Th17 cells in autoimmune diseases. Other cells, such as NK and regulatory T cells, have been implicated in autoimmunity and have been evaluated to ascertain their possible role in AS. Moreover, several polymorphisms, mutations and deletions in the regulatory proteins, protein-coding regions, and promoter regions of different genes involved in immune responses have been discovered and evaluated for possible genetic linkages to AS. In this review, we analyze the features of HLA-B27 and the suggested mechanisms of its involvement in AS while also focusing on the characterization of the immune response and the identification of genes associated with AS.