-
Annals of Medicine Dec 2021Hook (TWH) has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases. However, the...
BACKGROUND
Hook (TWH) has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases. However, the multi-target mechanism of TWH on ankylosing spondylitis (AS) remains to be elucidated.
METHODS
Active components and their target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Meanwhile, AS-related targets were obtained from the Genecards Database. After overlapping, the targets of TWH against AS were collected. Then protein-protein interaction (PPI) network and core targets analysis were conducted through STRING network platform and Cytoscape software. Moreover, molecular docking methods were utilized to confirm the high affinity between TWH and targets. Finally, DAVID online tool was used to perform gene ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) pathway enrichment analysis of overlapping targets.
RESULTS
The TCMSP Database results showed that there were11 active components of TWH against AS. PPI network and core targets analysis suggested that ESR1, VEGF, ICAM-1, and RELA were key targets against AS. Moreover, molecular docking methods confirmed the high affinity between bioactive molecular of TWH and their targets in AS. At last, enrichment analysis indicated that TWH participates in various biological processes, such as cell-cell adhesion, regulation of cell-matrix adhesion, acute inflammatory response, via TNF-α, NF-κB and so forth signalling pathways.
CONCLUSION
Verified by network pharmacology approach based on data mining and molecular docking methods, multi-target drug TWH may serve as a promising therapeutic candidate for AS but still needs further / experiments.
Topics: Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Molecular Docking Simulation; Network Pharmacology; Spondylitis, Ankylosing
PubMed: 34259096
DOI: 10.1080/07853890.2021.1918345 -
Best Practice & Research. Clinical... Sep 2023With back pain as one of the most common complaints in the population and with no single disease feature with sufficient sensitivity and specificity to diagnose axial... (Review)
Review
With back pain as one of the most common complaints in the population and with no single disease feature with sufficient sensitivity and specificity to diagnose axial spondyloarthritis (axSpA) on its own, diagnosing axSpA can be challenging. In this article, we discuss clinical, laboratory, and imaging spondyloarthritis features that can be used in diagnosis and explain the general principles underlying an axSpA diagnosis. Moreover, we discuss three pitfalls to avoid when diagnosing axSpA: i) using classification criteria as diagnostic criteria, ii) making a diagnosis by simple counting of spondyloarthritis features, and iii) over-reliance on imaging findings. Finally, we have some advice on how to build diagnostic skills and discuss new developments that may help facilitate the diagnosis of axSpA in the future.
Topics: Humans; Spondylarthritis; Back Pain; Axial Spondyloarthritis; Spondylitis, Ankylosing; Magnetic Resonance Imaging
PubMed: 37714776
DOI: 10.1016/j.berh.2023.101871 -
International Journal of Molecular... Mar 2023Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone... (Review)
Review
Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.
Topics: Humans; Spondylarthritis; Immunity, Innate; HLA-B27 Antigen; Lymphocytes; Axial Spondyloarthritis
PubMed: 37047435
DOI: 10.3390/ijms24076463 -
Frontiers in Immunology 2023Epidemiologic evidence has demonstrated a correlation between ankylosing spondylitis and psychiatric disorders. However, little is known about the common genetics and...
BACKGROUND
Epidemiologic evidence has demonstrated a correlation between ankylosing spondylitis and psychiatric disorders. However, little is known about the common genetics and causality of this association. This study aimed to investigate the common genetics and causality between ankylosing spondylitis (AS) and psychiatric disorders.
METHODS
A two-sample Mendelian Randomization (MR) analysis was carried out to confirm causal relationships between ankylosing spondylitis and five mental health conditions including major depressive disorder (MDD), anxiety disorder (AXD), schizophrenia (SCZ), bipolar disorder (BIP), and anorexia nervosa (AN). Genetic instrumental variables associated with exposures and outcomes were derived from the largest available summary statistics of genome-wide association studies (GWAS). Bidirectional causal estimation of MR was primarily obtained using the inverse variance weighting (IVW) method. Other MR methods include MR-Egger regression, Weighted Median Estimator (WME), Weighted Mode, Simple Mode, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO). Sensitivity analyses are conducted to estimate the robustness of MR results.
RESULTS
The findings suggest that AS may be causally responsible for the risk of developing SCZ (OR = 1.18, 95% confidence interval = (1.06, 1.31), P = 2.58 × 10) and AN (OR = 1.32, 95% confidence interval = (1.07, 1.64), P = 9.43 × 10). In addition, MDD, AXD, SCZ, AN, and BIP were not inversely causally related to AS (all p > 0.05).
CONCLUSION
Our study provides fresh insights into the relationship between AS and psychiatric disorders (SCZ and AN). Furthermore, it may provide new clues for risk management and preventive interventions for mental disorders in patients with AS.
Topics: Humans; Spondylitis, Ankylosing; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Mental Disorders
PubMed: 37954601
DOI: 10.3389/fimmu.2023.1277959 -
Medicine Apr 2016Ankylosing spondylitis (AS) is a common and genetically heterozygous inflammatory rheumatic disease characterized by new bone formation, ankylosis and inflammation of... (Review)
Review
Ankylosing spondylitis (AS) is a common and genetically heterozygous inflammatory rheumatic disease characterized by new bone formation, ankylosis and inflammation of hip, sacroiliac joints and spine. Until now, there is no method for early diagnosis of AS and the effective treatment available for AS patients remain largely undefined.We searched articles indexed in PubMed (MEDLINE) database using Medical Subject Heading (MeSH) or Title/Abstract words ("microRNA" and "ankylosing spondylitis") from inception up to November 2015.Genetic polymorphisms of miRNAs and their targets might alter the risk of AS development whereas certain miRNAs exhibit correlation with inflammatory index.Let-7i and miR-124 were upregulated whereas miR-130a was downregulated in circulating immune cells of AS patients. These deregulated miRNAs could modulate key immune cell functions, such as cytokine response and T-cell survival.miRNA deregulation is key to AS pathogenesis. However, clinical utilization of miRNAs for management of AS patients requires further support from future translational studies.
Topics: Humans; MicroRNAs; Spondylitis, Ankylosing
PubMed: 27057910
DOI: 10.1097/MD.0000000000003325 -
Clinical Rheumatology Oct 2023Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of... (Review)
Review
Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of this important aspect of axial spondyloarthritis, we conducted a systematic literature search of all articles published between January 2000 and 25 May 2023 on cardiovascular manifestations. Using PubMed and SCOPUS, 123 out of 6792 articles were identified and included in this review. Non-radiographic axial spondyloarthritis seems to be underrepresented in studies; thus, more evidence for ankylosing spondylitis exists. All in all, we found some traditional risk factors that led to higher cardiovascular disease burden or major cardiovascular events. These specific risk factors seem to be more aggressive in patients with spondyloarthropathies and have a strong connection to high or long-standing disease activity. Since disease activity is a major driver of morbidity, diagnostic, therapeutic, and lifestyle interventions are crucial for better outcomes. Key Points • Several studies on axial spondyloarthritis and associated cardiovascular diseases have been conducted in the last few years addressing risk stratification of these patients including artificial intelligence. • Recent data suggest distinct manifestations of cardiovascular disease entities among men and women which the treating physician needs to be aware of. • Rheumatologists need to screen axial spondyloarthritis patients for emerging cardiovascular disease and should aim at reducing traditional risk factors like hyperlipidemia, hypertension, and smoking as well as disease activity.
Topics: Male; Humans; Female; Spondylarthritis; Cardiovascular Diseases; Artificial Intelligence; Risk Factors; Spondylitis, Ankylosing; Heart Disease Risk Factors
PubMed: 37418034
DOI: 10.1007/s10067-023-06655-z -
Arthritis Research & Therapy May 2023Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here.
METHODS
In the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0-8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0-72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0-24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0-69).
RESULTS
Overall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, - 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], - 1.23 [2.81] vs - 0.37 [1.90] with placebo) was sustained through week 104 (- 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104).
CONCLUSION
Structural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02696031.
Topics: Adult; Humans; Non-Radiographic Axial Spondyloarthritis; Spondylitis, Ankylosing; Spondylarthritis; Sacroiliac Joint; Magnetic Resonance Imaging; Inflammation; Sacroiliitis
PubMed: 37194094
DOI: 10.1186/s13075-023-03051-5 -
The Korean Journal of Internal Medicine Sep 2023We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical...
We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5-12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13-16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis; Republic of Korea; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 37482652
DOI: 10.3904/kjim.2023.194 -
Scientific Reports Aug 2023Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal... (Randomized Controlled Trial)
Randomized Controlled Trial
Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = - 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.
Topics: Female; Humans; Spondylitis, Ankylosing; Endometriosis; Genome-Wide Association Study; Retrospective Studies; Infertility
PubMed: 37591939
DOI: 10.1038/s41598-023-40647-y -
Best Practice & Research. Clinical... Sep 2023Diagnostic delay in axial spondylarthritis (axSpA) remains an unacceptable worldwide problem; with evidence suggesting significant detrimental impact both clinically on... (Review)
Review
Diagnostic delay in axial spondylarthritis (axSpA) remains an unacceptable worldwide problem; with evidence suggesting significant detrimental impact both clinically on the individual, and economically on society. There is therefore, a need for global action across various healthcare professions that come into contact with patients living, and suffering, with undiagnosed axSpA. Recent estimates of the median diagnostic delay suggest that globally, individuals with axSpA wait between 2 and 6 years for a diagnosis - revealing a clear benchmark for improvement. This timespan presents a window of opportunity for earlier diagnosis and intervention, which will likely improve patient outcomes. This review describes the current diagnostic delay as estimated across countries and over time, before presenting evidence from published strategies that may be implemented to improve this delay across primary and secondary care, including for specialties treating extra-musculoskeletal manifestations of axSpA (ophthalmology, gastroenterology, dermatology). Ongoing campaigns tackling delayed diagnosis in axSpA are also highlighted.
Topics: Humans; Spondylarthritis; Delayed Diagnosis; Axial Spondyloarthritis; Early Diagnosis; Spondylitis, Ankylosing
PubMed: 37658016
DOI: 10.1016/j.berh.2023.101870