Comparison of established and preliminarily proposed ASAS MRI working group cut-offs for inflammatory MRI lesions in the sacroiliac joints in radiographic and non-radiographic axial spondyloarthritis.

BACKGROUND: A consensus definition for active sacroiliitis by MRI, mentioned in the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA), was published in 2009 and included a qualitative and quantitative MRI cut-off component. In 2021, updates to the quantitative component were preliminarily proposed. This post hoc analysis of part A of the phase 3 open-label C-OPTIMISE study (NCT02505542) explores the differences by applying the 2009 and preliminary 2021 inflammatory cut-offs on clinical outcomes of axSpA patients treated with certolizumab pegol. METHODS: Baseline MRI scans were used to classify 657 patients as MRI+ or MRI- according to the quantitative components of the 2009 and preliminary 2021 MRI cut-offs for inflammatory lesions. Clinical outcomes, including ASAS ≥40% improvement (ASAS40), Ankylosing Spondylitis Disease Activity Score and Bath Ankylosing Spondylitis Disease Activity Index, were reported to week 48. RESULTS: Across all analysed outcomes, 2009 MRI+ and preliminary 2021 MRI+ subgroups showed similar results. Notably, clinical outcomes for the discordant group (2009 MRI+but preliminary 2021 MRI- group; 53/657 [8.1%]) were close to those seen in MRI- patients according to either 2009 or preliminary 2021 inflammatory cut-offs, and notably different from the totality of MRI+ subgroups. CONCLUSION: This analysis suggests that the preliminary 2021 cut-offs for MRI inflammatory lesions may slightly increase the specificity of the quantitative part of the 2009 MRI inflammatory lesion definition. The effects of the updated MRI cut-offs need to be assessed on the basis of efficacy outcomes and with the inclusion of aspects of structural changes. TRIAL REGISTRATION NUMBER: NCT02505542.

Treatment strategies for Spondyloarthritis: Implementation of precision medicine - Or "one size fits all" concept?

Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.

Large-scale genome-wide association studies reveal the genetic causal etiology between ankylosing spondylitis and risk of leukemia and lymphocytic malignancies.

Background: Evidence from multiple observational studies suggests that ankylosing spondylitis (AS) is associated with leukemia and lymphocytic malignancies. However, the obtained results are inconsistent, and the causal relationship still needs to be determined. In this context, we utilized two-sample Mendelian randomization (MR) to investigate potential causal associations between AS and leukemia and lymphocytic malignancies. Methods: The analysis was conducted through published genome-wide association studies (GWAS). We obtained genetic data on AS as the exposure and leukemia, including lymphocytic leukemia, myeloid leukemia, and lymphocytic malignancies including lymphoma, multiple myeloma (MM) as the endpoint. The main method to evaluate causality in this analysis was the inverse variance weighting (IVW) technique. Additionally, we employed the weighted mode, weighted median, and MR-Egger regression for supplementary analyses. Finally, heterogeneity tests, sensitivity analyses, and multi-effect analyses are carried out. Results: In a random-effects IVW analysis, we found that genetic susceptibility to AS was associated with an increased risk of leukemia (OR = 1.002; 95%CI, 1.001-1.003; p = 0.003) and an increased risk of lymphocytic leukemia [OR = 1.001; 95% CI, (1.000-1.002), p = 0.008]. There was no evidence that AS was associated with lymphoma, myeloid leukemia, and MM. Conclusion: Our research indicates that AS was associated with an elevated risk of leukemia, and further analysis of specific types of leukemia showed that the risk of lymphocytic leukemia was associated with AS. Our findings highlight the importance of active intervention and monitoring to mitigate leukemia, especially lymphocytic leukemia risk in patients with AS.

Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status.

INTRODUCTION: Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening. METHODS: Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10 (PsA only) mg twice daily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction. RESULTS: PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1 tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs. CONCLUSIONS: In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616.

Evaluation of the efficacy of unilateral biportal endoscopic lamina osteotomy replantation assisted by ultrasonic bone scalpel in the treatment of lumbar infectious spondylitis.

OBJECTIVE: To analyze the clinical efficacy of ultrasonic bone scalpel (UBS)-assisted unilateral biportal endoscopic lamina osteotomy replantation (ULOR) for treating lumbar infectious spondylitis (LIS). METHODS: We conducted a retrospective analysis of patients with LIS who had therapy with UBS-assisted ULOR at our hospital between January 2020 and May 2023. A total of 17 instances matched the inclusion criteria, consisting of 7 females and 10 males. The UBS was utilized during surgery to extract the lamina completely followed by large bone grafting to fuse the cleaned intervertebral space. The study recorded and analyzed various parameters in the included patients before and after surgery. RESULTS: All 17 patients underwent a successful operation with an average duration of 136.82 ± 21.35 minutes, average blood loss of 77.43 ± 10.19 ml, and an average follow-up period of 18.55 ± 3.47 months. Following the surgical intervention, the patients experienced a substantial improvement in their clinical symptoms, accompanied by a significant drop in WBC, ESR, and CRP levels (all P<0.001). The postoperative VAS scores and ODI showed considerable improvement (both P<0.001). The postoperative Cobb angle and intervertebral space height were significantly corrected (P<0.001). At the last follow-up, the success rate of lumbar fusion was 100% and there were no instances of infection recurring. CONCLUSION: The use of ULOR, with assistance from UBS, for the treatment of LIS has proven to be beneficial. It provides significant relief from symptoms and corrects lumbar deformity. This surgical procedure is both effective and safe.

Converting an HLA-B27 flow assay from the BD FACSCanto to the BD FACSLyric.

HLA-B27 is a major histocompatibility complex (MHC) class I antigen which exhibits strong association (90%) with ankylosing spondylitis. HLA-B27 detection in patients by flow cytometry is a widely used clinical test, performed on many different flow cytometer models. We sought to develop and validate a test conversion protocol for the HLA-B27 test performed on the BD FACSCanto to BD's newer FACSLyric flow cytometers. The development and validation experiments were performed using anti-HLA-B27*FITC/CD3*PE antibody-stained whole blood patient specimens. The anti-HLA-B27*FITC logarithmic median fluorescence (LMF) results on the BD FACSCanto were converted to median fluorescence intensity (MFI) values on the BD FACSLyric. Clustering of the HLA-B27 positive and negative values, using a 3rd order polynomial equation, resulted in a conversion of the BD FACSCanto cutoff values, negative (<150 LMF) and positive (≥160 LMF), to negative (<4530 MFI) and positive (≥6950 MFI) on the BD FACSLyric. Accuracy was assessed by comparing the flow results obtained on the BD FACSCanto and BD FACSLyric to a molecular PCR based assay. Additional validation parameters (compensation verification, intra- and inter-assay precision, and instrument comparison) were performed per the recommendations outlined in the Clinical and Laboratory Standards Institute (CLSI) H62 guidelines for validation of flow cytometry assays.

Complementary App-Based Yoga Home Exercise Therapy for Patients With Axial Spondyloarthritis: Usability Study.

BACKGROUND: Axial spondyloarthritis (AS) is a chronic inflammatory rheumatic disease characterized by potentially disabling inflammation of the spine and adjacent joints. Regular exercise is a cornerstone of treatment. However, patients with AS currently have little support. YogiTherapy (MaD Lab) is an app developed to support patients with AS by providing instructions for yoga-based home exercise therapy. OBJECTIVE: This study aimed to evaluate the usability and acceptance of the newly designed YogiTherapy app for patients with AS. METHODS: Patients completed the User Version of the Mobile Application Rating Scale (uMARS) and net promoter score (NPS) questionnaires after the app introduction. Wilcoxon Mann-Whitney rank sum test, chi-square test for count data, and correlation analysis were conducted to examine the usability of the app, acceptance, and patient characteristics. RESULTS: A total of 65 patients with AS (33, 51% female; age: mean 43.3, SD 13.6 years) were included in the study from May 2022 to June 2023. Subsequently, the data were analyzed. Usability was rated moderate, with a mean uMARS of 3.35 (SD 0.47) points on a scale from 0 to 5. The highest-rated uMARS dimension was information (mean 3.88, SD 0.63), followed by functionality (mean 3.84, SD 0.87). Females reported a significantly higher uMARS total score than males (mean 3.47, SD 0.48 vs mean 3.23, SD 0.45; P=.03, Vargha and Delaney A [VDA] 0.66, 95% CI 0.53-0.77). The mean average of the NPS was 6.23 (SD 2.64) points (on a scale from 0 to 10), based on 43% (26/65 nonpromoters, 42% (25/65) indifferent, and 15% (9/65) promoters. A total of 7% (5/65) of those surveyed did not answer the question. When applying the NPS formula, the result is -26%. The NPS showed a positive correlation with the usage of mobile apps (r=0.39; P=.02). uMARS functionality was significantly higher rated by patients younger than 41 years (mean 4.17, SD 0.55 vs mean 3.54, SD 1; P<.001; VDA 0.69, 95% CI 0.56-0.80). Patients considering mobile apps as useful reported higher uMARS (r=0.38, P=.02). The uMARS app quality mean score was correlated with the frequency of using apps (r=-0.21, P<.001). CONCLUSIONS: The results revealed moderate acceptance and usability ratings, prompting further app improvement. Significant differences were observed between age and gender. Our results emphasize the need for further improvements in YogiTherapy.

Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders.

OBJECTIVES: This study aims to elucidate the microbial signatures associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), compared with colorectal cancer (CRC), to identify unique biomarkers and shared microbial mechanisms that could inform specific treatment protocols. METHODS: We analysed metagenomic datasets from patient cohorts with six autoimmune conditions-SLE, IBD, multiple sclerosis, myasthenia gravis, Graves' disease and ankylosing spondylitis-contrasting these with CRC metagenomes to delineate disease-specific microbial profiles. The study focused on identifying predictive biomarkers from species profiles and functional genes, integrating protein-protein interaction analyses to explore effector-like proteins and their targets in key signalling pathways. RESULTS: Distinct microbial signatures were identified across autoimmune disorders, with notable overlaps between SLE and IBD, suggesting shared microbial underpinnings. Significant predictive biomarkers highlighted the diverse microbial influences across these conditions. Protein-protein interaction analyses revealed interactions targeting glucocorticoid signalling, antigen presentation and interleukin-12 signalling pathways, offering insights into possible common disease mechanisms. Experimental validation confirmed interactions between the host protein glucocorticoid receptor (NR3C1) and specific gut bacteria-derived proteins, which may have therapeutic implications for inflammatory disorders like SLE and IBD. CONCLUSIONS: Our findings underscore the gut microbiome's critical role in autoimmune diseases, offering insights into shared and distinct microbial signatures. The study highlights the potential importance of microbial biomarkers in understanding disease mechanisms and guiding treatment strategies, paving the way for novel therapeutic approaches based on microbial profiles. TRIAL REGISTRATION NUMBER: NCT02394964.

Corrigendum: Real-world experience with secukinumab in the entire axial spondyloarthritis spectrum.

[This corrects the article DOI: 10.3389/fmed.2023.1156557.].

Posture, balance and gait in axial spondyloarthritis: a case-control study.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily involves the axial skeleton but may also present with peripheral joint involvement and extra-articular involvement. The present study aims to quantitatively analyze posture, balance, and gait parameters in patients with axSpA and and assess associated factors. This cross-sectional case-control study included 51 axSpA patients (30 males, 21 females; mean age 40.94 ± 10.48 years) and 51 age- and sex-matched healthy controls. In patients with axSpA, the Ankylosing Spondylitis Disease Activity Score CRP, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Maastrich Ankylosing Spondylitis Enthesitis Score (MASES), and the Ankylosing Spondylitis Quality of Life (ASQoL) scale were used. For postural analysis, DIERS formetric (Diers GmbH, Schlangenbad, Germany) videoraster- stereography device was utilized. HUR SmartBalance BTG4 (HUR-labs Oy, Kokkola, Finland) balance platform was used for postural balance and limit of stability (LOS) measurement. Participants were evaluated using Berg Balance Scale (BBS), Functional Reach Test (FRT) and Timed Up and Go Test (TUG). The Zebris FDM type 3 (Zebris Medical GmbH, Germany) walking platform was used to measure the spatiotemporal parameters of the participants. Comparison of postural parameters showed that sagittal imbalance and cervical depth distance were increased in the axSpA group than in the healthy participants (p < 0.004). Comparison of functional balance parameters showed that BBS and FRT scores were significantly lower (p < 0.001) in the axSpA group than in the control group, while TUG scores were significantly higher (p < 0.001). The LOS values, which evaluate dynamic balance were significantly lower, indicating impairment, in the axSpA group. In the measurement of postural sway, which indicates static balance, all 23 subparameters were found to be similar. When analyzing the spatiotemporal gait parameters, in the axSpA group compared with those in the control group; Foot angles (p= 0.028) and stride width (p = 0.004) were increased, whereas step lengths (p = 0.004) and stride lengths (P = 0.004) were decreased. In the axSpA group the gait speed was decreased (p = 0.004). When axSpA was analyzed separately as radiographic and nonradiographic axSpA, similar findings were observed in posture, balance, and gait parameters. No significant difference was observed. We found that the clinical assessments most closely associated with posture, balance, and gait analyses were BBS, FRT, TUG, and BASFI.

Distinct clinical outcomes linked to peripheral arthritis and dactylitis in axial spondyloarthritis: findings from a retrospective Irish cohort.

INTRODUCTION: Axial spondyloarthritis (AxSpA) is a chronic inflammatory condition primarily affecting the axial skeleton. Peripheral features such as peripheral arthritis (PA) and dactylitis are common in AxSpA disease. This study aimed to investigate the independent impact of these manifestations on patient presentation and disease outcomes within an Irish AxSpA cohort. METHODS: 912 Irish AxSpA patients were analyzed in this study. Disease outcomes in patients with and without peripheral arthritis or dactylitis were compared using univariate and multivariate methods. The prevalence of extra-spinal manifestations was further assessed in relation to AxSpA disease duration. RESULTS: 30.2% of patients reported PA, while 6.6% had dactylitis. PA and dactylitis were strongly linked, with 70% of patients presenting with dactylitis also showing features of PA. Psoriasis was more common in both patients with PA (OR 2.2, P < 0.001) and dactylitis (OR 3.38, P < 0.001). Dactylitis, but not PA was strongly linked to uveitis (OR 2.91, P < 0.001) and inflammatory bowel disease (OR 3.15, P < 0.001), while PA was associated with worse patient functioning and reduced quality of life. PA, but not dactylitis was linked with increased AxSpA disease duration. DISCUSSION: Despite high concurrence of PA and dactylitis in AxSpA patients, each manifestation is independently associated with worse outcomes. While some of these overlapped, several outcomes are specific to either PA or dactylitis. Due to its strong association with uveitis and inflammatory bowel disease, an early presentation of dactylitis may represent a unique subset of patients and serve as a valuable predictive marker for the later onset of these conditions.

Risk of motor vehicle accidents with profound injuries in patients with ankylosing spondylitis: a nationwide, population-based cohort study.

Background: Patients with ankylosing spondylitis (AS) suffer from impaired physical activity and are prone to motor vehicle accidents (MVA), but definite instruction regarding the relationship between disease evolvement and MVA and potential risk factors is lacking. Objectives: To explore the risk factors and their impact on recorded MVA with profound injuries in AS patients with prescriptions. Design: Nationwide, population-based, matched retrospective cohort study. Methods: Using Taiwanese administrative healthcare databases, with available claims data from 2003 to 2013, we selected 30,911 newly diagnosed adult AS patients with concurrent prescriptions from 2006 to 2012 as AS patients, along with 309,110 non-AS individuals as the control group, matched in gender, age at index date and year of the index date. The risk of recorded MVA with profound injuries was compared between the two groups in terms of incidence rate ratio (IRR) and log-rank test p-value. Using Cox regression analysis, we studied associations between the risk and AS diagnosis. Results: The risk of recorded MVA with profound injuries in AS patients was significantly higher than in non-AS individuals, specifically 2 years after AS diagnosis (IRR, 2.00; 95% confidence interval (CI), 1.42-2.81). For patients with follow-up periods >2 years, the adjusted risk was positively associated with suburban residence (adjusted hazard ratio (aHR), 2.18; 95% CI, 1.55-3.06), rural residence (aHR, 1.89; 95% CI, 1.27-2.80), lower insured income (aHR, 1.35; 95% CI, 1.01-1.81) and recorded MVA with profound injuries before AS diagnosis (aHR, 6.16; 95% CI, 2.53-14.96). AS diagnosis (aHR, 1.81; 95% CI, 1.27-2.59) and frequency of ambulatory visits (aHR, 1.01; 95% CI, 1.004--1.02) were specific associated factors for them compared with those with follow-up periods ⩽2 years. Conclusion: For adult AS patients in Taiwan, factors such as AS disease evolution and frequent ambulatory visits for disease control in the second year of the disease course may significantly increase the risk of recorded MVA with profound injuries beyond 2 years after AS diagnosis.

Successful Treatment of Complicated Pyogenic Spondylitis Due to Advanced Rectosigmoid Cancer Utilizing Vigorous Antibiotic Therapy and Minimally Invasive Robotic Colorectal Surgery: A Case Report.

We report a case of rectosigmoid cancer complicated by pyogenic spondylitis. The patient was a 71-year-old man who had anemia and back pain. Endoscopy revealed a rectosigmoid tumor, confirmed to be well-differentiated adenocarcinoma. Imaging indicated rectosigmoid cancer with pyogenic spondylitis at the L1 vertebra. We performed radical resection (robotic-assisted Hartmann's procedure) after controlling the inflammation caused by pyogenic spondylitis. Colon cancer complicated by pyogenic spondylitis is rare. Here, we describe the mechanisms of this infection and treatment strategies along with a review of the literature.

Unraveling Shared Diagnostic Biomarkers of Fibromyalgia in Ankylosing Spondylitis: Evidence from Comprehensive Bioinformatic Analysis and Experimental Validation.

Background: Fibromyalgia (FM) is a commonly encountered disease featuring chronic generalized pain, sleep disorder, and physical fatigue. Ankylosing spondylitis (AS) causes chronic lumbodorsalgia involving the sacroiliac joint, often clinically complicated with FM. Nevertheless, the pathophysiology of FM secondary to AS is still lacking. Methods: Gene expression data of the whole blood in FM and AS patients were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were evaluated employing the "limma" package. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to explore common pathways. Weighted gene correlation network analysis (WGCNA) was adopted to screen key gene modules. Three machine learning algorithms were performed to refine the intersected genes. Single sample gene set enrichment analysis (ssGSEA) was applied to explore the relationships between hub genes and immune cells. The dependability of hub gene expressions in clinical blood specimens was verified by RT-PCR. Molecular docking was conducted to predict small molecular compounds targeting hub genes. Results: DEG analysis screened 419 shared up-regulated and 179 shared down-regulated genes in FM and AS. A total of 143 common genes in positive modules of AS and FM were identified via WGCNA. Six key genes (CETN3, CACNA1E, OGT, QRFPR, SCOC, DIAPH1) were obtained by intersecting the WGCNA-derived shared genes and up-regulated DEGs. CETN3 and CACNA1E were refined as hub genes via three machine-learning algorithms and they showed excellent diagnostic value for FM and AS. However, ssGSEA exhibited different immune cell infiltration patterns in FM and AS. Gabapentin enacarbil was recognized as a potential therapeutic drug for AS-FM patients. Conclusion: This study reveals the shared hub genes in AS and FM. Meanwhile, these results were confirmed in clinical samples. CETN3 and CACNA1E may become potential diagnostic biomarkers and therapeutic targets for patients with AS complicated by FM.

Exploration of Potential Therapeutic Targets of Shentong Zhuyu Decoction for Ankylosing Spondylitis Based on Network Pharmacology and Molecular Docking.

Objective: This study aimed to explore the potential active components and therapeutic targets of Shentong Zhuyu Decoction (SZD) in the treatment of ankylosing spondylitis (AS) through network pharmacology and animal experiments. Methods: Targets for AS and related pathways were obtained by network pharmacology, and the pathways with the best binding affinity in molecular docking were verified by animal experiments. Results: The network pharmacology analysis found 248 chemical components, 1068 drug targets and 803 AS-related targets in SZD. After intersection targets analysis, 116 common drug-disease targets were obtained, and matrix metalloproteinase-9, nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) and cytochrome P450 2D6 were identified as the key targets of SZD for the treatment of AS. A total of 2152 biological processes, 38 cellular component expressions and 150 molecular function terms were obtained in gene ontology enrichment analysis, and 153 Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathways were obtained in KEGG enrichment analysis. Molecular docking analysis showed that the absolute binding energies of glypallichalcone and NLRP3, quercetin and NLRP3 and kaempferol and NLRP3 were >7. Animal experiments showed that the expressions of NLRP3, Caspase-1, interleukin (IL)-1ß and IL-18 were significantly increased in the model group and the treatment group compared with those in the blank group, and the expression levels in the treatment group were significantly decreased compared with those in the model group (p < 0.05). Conclusion: The active components in SZD, such as baicalin, quercetin, kaempferol and glypallichalcone, may reduce the expression of IL-1ß and IL-18 via the NLRP3/Caspase-1 signalling pathway to inhibit the development and progression of inflammation and play a role in the treatment of AS.

A higher body mass index and increased syndesmophytes volume are associated with facet joints ankylosis on thoracic spine in patients with ankylosing spondylitis: a retrospective cohort study.

OBJECTIVE: To investigate the association between syndesmophytes and facet joint (FJ) lesions in patients with ankylosing spondylitis (AS), and to identify clinical factors associated with FJ ankylosis (FJA) in thoracic segment. METHODS: Ninety-seven patients with AS who underwent thoracic spine computed tomography (CT) or chest CT and without completely thoracic spine fusion were included. FJ lesions were analyzed for the numbers and distribution of normal, ankylosis, erosions, joint-space narrowing, osteophytes, and subchondral sclerosis. The volume of vertebral syndesmophtes unit (VSU) and total thoracic syndesmophtes volume were separately calculated by Mimics software. Clinical factors associated with FJA were investigated using generalized estimation equation (GEE). The association between syndesmophtes volume and numbers of FJ structural lesions was analyzed using generalized additive mixed model (GAMM). RESULTS: 2328 FJ and 1164 VSUs in thoracic spine were assessed. The majority FJ structural lesions were ankylosis (32.39%). FJA was more frequently seen in vertebrae with syndesmophytes formation (p < 0.001). GEE showed that patients with normal BMI (18.5-24.9 kg/m2) and high BMI (> 24.9 kg/m2) were more likely to have FJA in thoracic spine (odds rations [95% confidence interval]: 0.27(0.12-0.59), 1.45(1.03-8.57), respectively). GAMM showed that syndesmophytes volume increase the numbers of FJA (standard ß = 0.009, p < 0.05) and decreased the numbers of normal FJ (standard ß = -0.07, p < 0.01). CONCLUSION: FJA was the most common FJ structural lesion in thoracic spine, and it increases linearly with syndesmophytes before the bridging syndesmophytes formed. A higher BMI (especially > 24.9 kg/m2) and increased syndesmophytes volume are associated with FJA in thoracic spine.

Knockdown of SIGLEC1 inhibits osteogenic differentiation to alleviate ankylosing spondylitis progression by suppressing the TGF-ß1/SMAD signaling pathway.

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease, which can result in disability in severe cases and endanger physical health. Two microarray datasets related to AS were selected from NCBI for bioinformatics analysis. Differentially expressed genes (DEGs) were screened and protein-protein interaction network was constructed to obtain hub genes. hSMSCs were injected with TNF-α to construct AS cell models. The hSMSCs were transfected with SIGLEC1 siRNA to silence SIGLEC1 expression. CCK-8, western blot, qRT-PCR, and ELISA were performed to detect the effects of SIGLEC1 knockdown on cell proliferation, osteogenic differentiation (ALP, BMP2, Osterix, and Runx2), inflammation (IL-23 and IL-6), and TGF-ß1/SMAD signaling pathway (SMAD3, SMAD7 and TGF-ß1). A TGF-ß1 activator was applied for feedback function assays. A total of 29 common DEGs were screened from GSE181364 and GSE221786, and the key gene SIGLEC1 was selected. Knockdown of SIGLEC1 promoted cell proliferation and inhibited ALP activity, the level of BMP2, Osterix and Runx2 in TNF-α-induced hSMSCs, as well as the decreased inflammatory factors IL-23 and IL-6. Furthermore, knockdown of SIGLEC1 inhibited the expression of TGF-ß1/SMAD signaling pathway related proteins, while the treatment of TGF-ß1 activator weakened the inhibiting effects of sh-SIGLEC1 on the osteogenic differentiation and inflammation in TNF-α-induced hSMSCs. In summary, knockdown of SIGLEC1 promoted cell proliferation and inhibited osteogenic differentiation and inflammation by inhibiting TGF-ß1/SMAD signaling pathway, thereby suppressing the development of AS.

Causality Between Ankylosing Spondylitis and Urolithiasis in European Populations: A Mendelian Randomization Analysis.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory condition affecting the spine. Observational studies have suggested a heightened risk of urolithiasis in AS patients. However, due to the inherent limitations of observational research, the causal relationship between the two remains to be determined. OBJECTIVE: Utilizing the Mendelian randomization analysis approach, this study sought to explore the causal link between AS and urolithiasis. METHODS: Data from genome-wide association studies were employed for analysis. Mendelian randomization analyses were conducted using the IVW, MR-Egger, Weighted Median, and Weighted Mode methods. Heterogeneity tests, sensitivity analyses, and pleiotropy analyses were also performed. RESULTS: The causality between AS and urolithiasis was supported by the IVW (P = .02), Weighted Median (P = .006), and Weighted Mode (P = .01) methods. The MR-Egger method (P = .07) did not support this causal relationship, yet its directionality was consistent with the other three methods. None of the four analysis methods supported a reverse causal relationship between AS and urolithiasis. CONCLUSION: Our study demonstrates a causal relationship between AS and urolithiasis, with no evidence of reverse causality. Given the increased risk of urolithiasis in AS patients, it is crucial to implement preventive strategies and early detection. Stone composition analysis should also be incorporated into clinical practice for these patients, as it can provide essential insights into the metabolic and genetic factors contributing to stone formation, thus improving diagnostic accuracy and treatment outcomes. Future studies are needed to further validate these findings and explore the detailed mechanisms involved.

Intervention of inflammation associated with ankylosing spondylitis by triptolide promotes histone H3 Iys-27 trimethylation.

Objective: This study aims to explore the effects of Triptolide (TP) on the differentiation of Th17 cells in ankylosing spondylitis (AS).Methods: Peripheral blood mononuclear cells (PBMCs) collected from 10 patients with active AS patients were exposed to TP, GSK-J4 or vehicle. T lymphocyte subsets were analyzed using flow cytometry. ELISA was used to assess the level of IL-17. Western blot analysis and quantitative RT-PCR were used to measure the mRNA and protein levels of RORγt, JMJD3, EZH2, JAK2 and STAT3 in the JAK2/STAT3 signaling pathway.Results: We observed a tendency toward a greater percentage of IL-17-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with active AS than in those from healthy controls. Triptolide (TP) and GSK-J4 significantly reduced IL-17 expression. In cultured PBMCs from patients with active AS, 24 h of treatment with TP or GSK-J4 decreased the expression of RORγt (p < 0.05), JAK2 and STAT3 (JAK2: p < 0.05; STAT3: p < 0.05). Furthermore, both triptolide and GSK-J4 increased the level of histone 3 with Lys 27 trimethylation (H3K27me3) in patient-derived PBMCs. H3K27me3 enrichment was detected at the promoters of the RORc, STAT3 and IL-17 genes. Consistent with this finding, triptolide upregulated the EZH2 gene and downregulated the JMJD3 gene.Conclusion: Triptolide inhibits Th17 cell differentiation via H3K27me3 upregulation and orchestrates changes in histone-modifying enzymes, including JMJD3 and EZH2. These findings support the clinical efficacy of triptolide for AS and may provide clues for identifying molecular targets for the development of novel treatments.

Extracellular Vesicles Derived from Ligament Tissue Transport Interleukin-17A to Mediate Ligament-To-Bone Crosstalk in Ankylosing Spondylitis.

Pathological new bone formation is a critical feature of the progression of ankylosing spondylitis (AS), and spine ankylosis is a distinctive feature of this condition. Ligaments are the primary regions of pathological new bone formation in AS. Here, it is demonstrated that ligament tissue-derived extracellular vesicles (EVs) and their interleukin-17A (IL-17A) cargo mediate the communication between the tissue and other cells. The investigation revealed that IL-17A in EVs can activate the JAK-STAT3 pathway, thereby stimulating the expression of MMP14 in AS ligament. Overexpression of MMP14 can lead to changes in the cytoskeleton and mechanical signaling of mesenchymal stem cells and other cells. These alterations in cellular cytoskeleton and mechanical signaling at ligament sites in patients with AS or in stem cells treated with EVs can result in pathological new bone formation. Finally, inhibiting IL-17A activity and EV endocytosis effectively controlled inflammation and pathological new bone formation. Overall, these data suggest that ligament-derived EVs and the enclosed IL-17A have a potential role in driving pathological new bone formation in AS, and targeting EVs may therefore emerge as a novel approach to delaying ectopic ossification in AS.