According to an epidemiological study, hip joint involvement was detected in 12–56% of patients with axial spondyloarthritis (axSpA) in Russia. Data on the incidence of coxitis in patients with axial psoriatic arthritis (axPsA) are lacking. The aim of the study was to compare radiographic changes in the hip joints in patients with axial spondyloarthritis and axial psoriatic arthritis and to evaluate the relationship between coxitis and disease activity. Material and methods. The study included 222 patients with a mean age of 35.7±12.7 years. The first group included 108 patients who met the 2009 ASAS (Assessment of SpondyloArthritis International Society) criteria for axSpA or the 1984 criteria for ankylosing spondylitis (AS); The second group included 114 patients with axPsA who met the CASPAR (ClASsification for Psoriatic ARthritis) criteria. Signs of axial involvement in psoriatic arthritis (PsA) were determined using instrumental imaging methods. Diagnosis required the presence of radiologically reliable sacroiliitis (SI), i.e., bilateral stage ≥II or unilateral stage ≥III according to Kellgren, or active sacroiliitis according to magnetic resonance imaging. The presence of at least one syndesmophyte (paraspinal ossificate) in the cervical (CS) or lumbar (LS) spine, as well as ankylosis of the facet joints of the CS, were also taken into account. The mean age of disease onset was 26.3±20.3 years; HLA-B27 was detected in 54% of patients. The diagnosis of coxitis was established based on a pelvic X-ray and calculation of the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI hip) for each joint. Results. Radiographic evidence of coxitis was detected in 52 of the 222 patients included in the study, including 22 patients with AS and 30 patients with axPsA. Patients with axPsA were older than those with axSpA (median age 32 years and 45 years, respectively; p<0.05). Radiographic coxitis was more common among men with axSpA and equally common among men and women with axPsA. The ASDAS (Axial Spondyloarthritis Disease Activity Score) index value was high in both groups; however, it was statistically significantly higher in patients with axPsA than in patients with axSpA (on average, 2.1 and 3.2, respectively; p<0.05). Acute phase indices (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) were slightly higher in axSpA than in axPsA (CRP – 5.8 and 4.2 mg/L; ESR – 20 and 17 mm/h, respectively), but these differences were not statistically significant (p>0.05). Functional impairment according to BASFI (Bath Ankylosing Spondylitis Functional Index) was more pronounced in axPsA than in patients with axSpA (p<0.05). Peripheral arthritis was also more common in patients with axPsA (96.6% and 59.0%, respectively; p<0.05). Conclusion. Radiographic coxitis was detected in 20% of patients with axSpA and 26% with axPsA. In previous studies, the incidence of radiographic coxitis in patients with psoriatic arthritis did not exceed 10%. According to our study, patients with axPsA had high clinical and laboratory indicators of disease activity, as well as significant functional impairment.

The circRNA0001707/miR-203a-3p/TLR4 regulatory axis drives macrophage polarization in enthesitis of newly diagnosed ankylosing spondylitis.

To assess the comparative risk of osteoporosis and fractures associated with biological disease-modifying anti-rheumatic drug (bDMARD) exposure in patients with ankylosing spondylitis (AS). This nationwide cohort study analyzed 37,708 patients with AS. The outcomes of interest were osteoporosis, vertebral fracture, and hip fracture, defined based on diagnosis codes. The follow-up period was from the AS diagnosis date to December 2021. Multivariable time-varying Cox regression models were used to assess the comparative risk of each outcome comparing tumor necrosis factor inhibitors (TNFi) vs. bDMARD-naïve; interleukin-17 inhibitors (IL-17i) vs. bDMARD-naïve; and IL-17i vs. TNFi. For comparing IL-17i vs. TNFi, we matched the line of bDMARD treatment between the TNFi and IL-17i groups in a 4:1 ratio. The TNFi (adjusted hazard ratio [aHR]=0.83, 95% confidence interval [CI]=0.76-0.90, p<0.01) and IL-17i (aHR=0.19, 95% CI=0.10-0.38, p<0.01) exposures were associated with lower osteoporosis risk compared with the bDMARD-naïve group. Further, IL-17i (aHR=0.23, 95% CI=0.11-0.46, p<0.01) was associated with lower osteoporosis risk than TNFi. The TNFi (aHR=0.64, 95% CI=0.59-0.70, p<0.01) exposure was associated with lower vertebral fracture risk than the bDMARD-naïve group. IL-17i (vs. bDMARD-naïve) was associated with lower vertebral fracture risk, although this did not reach statistical significance (aHR=0.52, 95% CI=0.25-1.09, p=0.09). Hip fracture risk did not differ across different groups. TNFi and IL-17i exposures may be associated with a lower risk of osteoporosis, but not hip fractures, compared with bDMARD-naïve. TNFi exposure, but not IL-17i exposure, may be associated with a lower risk of vertebral fracture compared with bDMARD-naïve.

To evaluate and compare the quality and readability of patient education materials (PEM) related to ankylosing spondylitis (AS) generated by four AI-based large language models (LLMs): ChatGPT-4o, ChatGPT-3.5, DeepSeek R1, and DeepSeek V3. On May 1, 2025, the ten most frequently searched AS-related questions were identified using Google Trends (Turkey). These questions were posed to the four LLMs, and the responses were recorded without modification. Quality was assessed by two independent rheumatologists. The quality was evaluated using the DISCERN tool. Readability and comprehensibility were assessed using the Flesch Reading Ease Score (FRES) and the Flesch-Kincaid Grade Level (FKGL). Inter-rater reliability was analyzed using the intraclass correlation coefficient (ICC). Mean scores and 95% confidence intervals (CI) were reported. ChatGPT-4o achieved the highest average DISCERN score (72.38), followed by DeepSeek R1 (69.76), ChatGPT-3.5 (68.82), and DeepSeek V3 (68.79). Inter-rater reliability for DISCERN was excellent (ICC, 0.931). ChatGPT-4o had the highest mean DISCERN score, although the difference was not statistically significant. For readability analysis, DeepSeek V3 had the highest FERS score (14.93). This suggested that DeepSeek V3 was more easily understandable than other LLMs. ChatGPT-3.5 received the lowest score (5.29). FKGL scores varied within a narrow range (15.33-15.93) across models. Therefore, it was interpreted that the data required university-level reading skills. ConclusionFor AS, AI-generated PEMs were generally complex enough to meet the needs of highly educated patients. The responses were information-dense and complex, requiring excessive expertise regardless of the recipient's educational level. In the future, improving the clarity and comprehensibility of the language according to personal characteristics (educational level, etc.) and providing evidence-based citations could help make LLMs more useful in clinical settings or for the public. Key Points • This study compared how different AI chatbots explain ankylosing spondylitis to patients. • Although the information quality was high, the language used was too complex for most patients. • ChatGPT-4o gave the most accurate content, while DeepSeek V3 used the easiest words. • Future AI tools should use simpler language and include reliable references to better support patient education.

Piezo1 at the crossroads: Mediating inflammation and mechanical stress in joint disorders.

Surgical management of thoracolumbar fractures in patients with ankylosing spinal disorders such as ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis remains debated. Although several studies have compared minimally invasive surgery to open fixation of thoracolumbar fractures in this patient population, a meta-analysis compiling the literature on this topic is lacking. Following the PRISMA guidelines, PubMed, Cochrane, and Google Scholar (pages 1 to 20) were accessed and explored until October 2024. The extracted data consisted of complications, mortality, surgery-related parameters, postoperative back pain, and postoperative Cobb angle. Across all studies, mean differences with 95% confidence intervals were used for continuous data, whereas odds ratio was used for dichotomous data. Eight retrospective articles were included in the meta-analysis, including 295 patients, with 164 in the MIS group and 131 in the open group. Patients undergoing minimally invasive fixation were found to have lower rates of overall complications (OR = 0.43; 95% CI, 0.25-0.75, P = 0.003), shorter surgical time (MD = -67.79; 95% CI, -91.61 to -43.96, P < 0.001) and hospital stay (MD = -14.08; 95% CI, -25.95 to -2.21, P = 0.02), and less blood loss (MD = -1.52; 95% CI, -2.70 to -0.33, P = 0.01). However, there was no difference in postoperative back pain or Cobb angle between the two groups. Patients undergoing MIS treatment of fractures through ankylosed spines had lower rates of complications, less EBL, and shorter surgical time and LOS, highlighting the potential benefits of minimally invasive fixation of thoracolumbar fractures. However, studies with longer-term follow-up to assess the longevity of MIS fixation are needed, and furthermore some injury patterns may not be amenable to MIS fixation. Also, some institutions may not have resources to provide MIS techniques, and open fixation remains a safe and reliable option for treatment.

A novel mouse model of arthritis with enthesitis and heterotopic ossification.

ABSTRACT Objective To investigate the impact of beliefs about biologic therapy on treatment response and to identify the factors associated with treatment beliefs in patients with axial spondyloarthritis (axSpA). Methods A total of 137 axSpA patients (62% male; mean age, 41.1 ± 12.1 years) initiating or switching biologic therapy participated in this observational study. Patients’ beliefs about biologic treatment were assessed using the Beliefs about Medicines Questionnaire (BMQ) at baseline and at 12 and 24 months. Treatment responses were evaluated using the Axial Spondyloarthritis Disease Activity Score – Clinically Important Improvement (ASDAS-CII) and the Bath Ankylosing Spondylitis Disease Activity Index 20 (BASDAI20). Associations between BMQ scores, treatment response, and related factors were analyzed using generalized estimating equations (GEE). Results BMQ-specific Concern scores were consistently lower than BMQ-specific Necessity scores. Although beliefs regarding Necessity and Harm did not change significantly over time, beliefs about Concern and Overuse did change, leading to an increase in the necessity – concern differential (NCD). Treatment response and biologic discontinuation were not significantly associated with BMQ scores in the longitudinal analyses. Multivariable GEE analyses revealed that Necessity beliefs were associated with enthesitis, dactylitis, and uveitis. Concern scores were predicted by peripheral arthritis, inflammatory bowel disease, and disease activity, while uveitis also influenced NCD, Overuse, and Harm beliefs. Dactylitis and older age were associated with increased Overuse and Harm scores. Additionally, both psoriasis and DMARD use were linked to higher Harm perceptions. The functional index was not a significant predictor in any model. Conclusion In this longitudinal analysis, the beliefs of axSpA patients about treatment varied significantly depending on their perceived treatment benefits and experience with biologic therapy. Furthermore, specific disease manifestations were shown to influence treatment-related beliefs.

To evaluate serum tartrate-resistant acid phosphatase 5b (TRACP5b) levels in patients with ankylosing spondylitis (AS) and primary osteoporosis (OP), and to assess its diagnostic value, correlations with bone mineral density (BMD) and disease activity, and its potential as a marker of secondary osteoporosis in AS. In this cross-sectional comparative study, 23 patients with AS, 24 patients with primary OP, and 20 healthy controls were recruited from Assiut University Hospitals. Demographic, clinical, laboratory, and dual-energy X-ray absorptiometry (DXA) data were collected. AS disease activity was assessed using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Serum TRACP5b was measured by ELIZA. Group differences, correlations, and ROC curve analysis were performed. AS patients were predominantly male and younger than OP patients. Primary OP patients had significantly lower DXA T-scores than AS patients (mean difference = 2.36, p < 0.001). TRACP5b levels were higher in AS patients than controls but not significantly different (p = 0.111). In AS, TRACP5b correlated with age (r = 0.534, p = 0.009) and disease activity (r = 0.427, p = 0.042) but not with BMD. ROC analysis showed moderate diagnostic performance for detecting secondary osteoporosis in AS (AUC = 0.653). No significant differences in TRACP5b or BMD were found across AS treatment groups. Serum TRACP5b may serve as a supplementary marker of osteoclast activity in AS and shows moderate diagnostic value for secondary osteoporosis, with levels more related to age and disease activity than BMD. Larger studies are needed to confirm its clinical utility. Key Points • Serum TRACP5b levels were higher in patients with AS than in healthy controls, though without consistent statistical significance, reflecting biological variability. • TRACP5b correlated positively with age and disease activity (BASDAI) in AS but not with BMD, disease duration, or ESR, highlighting its link to inflammatory bone resorption. • ROC analysis showed TRACP5b had moderate diagnostic performance for secondary osteoporosis in AS, but limited value in primary osteoporosis. • Our findings suggest that TRACP5b may serve as supplementary marker of bone turnover in AS, warranting further validation in larger, longitudinal studies.

Advanced glycation end products (AGEs), and particularly the unique AGE10 epitope, may be a potential biomarker of immunopathology in rheumatic diseases. They may be associated with inflammation, joint damage and ossification processes. AGE10 present in human and animal tissues could be detected with monoclonal antibody against melibiose-derived glycation product MAGE synthesized in anhydrous conditions. This MAGE product was different from the classic synthesis in water solution. The epitope was determined in serum with ELISA using these anti-MAGE monoclonal antibodies. This work aims to determine serum AGE10 levels in patients with reactive arthritis (ReA)-caused with Chlamydia trachomatis (group 2) and ReA with C. trachomatis during the reactivation of EBV infection (group 3). Additionally, ankylosing spondylitis (AS) patients (group 4) were involved in the study, due to the potential evolution of ReA toward AS. The control group maintained physiological AGE10 levels (316µg/ml), while the combined infection group showed elevated AGE10 (850µg/ml) compared to the chlamydial-only group (17µg/ml). Fluorescent fAGE were at the highest level in AS patients. A striking finding was the complete absence of detectable AGE10 antigen in the AS group, coinciding with notably elevated immune complex AGE10-anti-AGE10 levels. A similar pattern was observed in patients with ReA caused by C. trachomatis alone (Group 2), albeit to a lesser extent. In contrast, both the control group and patients with ReA associated with EBV coinfection (group 3) displayed an inverse relationship, characterized by higher antigen levels and lower immune complex concentrations. Thus, diminished level of AGE10 could be caused, besides local accumulation, also by immune complexes formation, a pathogenic factor. Therefore, evaluating disease activity in ReA and AS is crucial to further our understanding of the pathophysiology of AGEs formation and predicting prognosis.

ABSTRACT Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen B27 (HLA-B27), yet how this genetic risk factor interacts with the gut microbiome remains unclear. We integrated fecal gut microbiota analysis, untargeted metabolomics, and clinical phenotyping in 88 participants, including HLA-B27–positive patients with AS (n = 28), HLA-B27–positive healthy controls (n = 30), and HLA-B27–negative healthy controls (n = 30). HLA-B27 positivity, particularly in AS, was associated with marked alterations in gut microbial composition and metabolic profiles, with forty bacterial species showing progressive disease-related shifts across cohorts. Integrated pathway and metabolomic analyses identified three amino acid–related pathways consistently disrupted in AS: tryptophan metabolism, cysteine metabolism, and pyruvate-centered biosynthesis of branched-chain amino acids, ornithine, and lysine. Correlation network analyses linking differential taxa, metabolites, and clinical indices revealed previously unrecognized microbial and metabolic signatures that robustly distinguished AS from both control groups. To explore causality, fecal microbiota transplantation (FMT) from clinical donors into antibiotic-treated mice recapitulated key disease-relevant features, including impaired intestinal barrier function, systemic inflammation, trabecular bone loss, and polarization of macrophages toward a proinflammatory M1 phenotype. Mechanistic validation identified cinnabarinic acid as a critical microbial-derived metabolite that suppresses M1 macrophage polarization via activation of the aryl hydrocarbon receptor (AhR) pathway and confers protection in the FMT model. Together, these findings support a model in which HLA-B27–associated gut dysbiosis and metabolic reprogramming promote AS pathogenesis through macrophage-mediated inflammation and osteocatabolic signaling, highlighting microbial–metabolic pathways as potential therapeutic targets.

Abstract Cauda equina syndrome (CES) associated with dural ectasia is a rare manifestation in patients with ankylosing spondylitis (AS). We report a case of a 53-year-old female with a 10-year history of AS who developed CES in the past 1 year. The CT and MRI findings revealed the unique appearances of dural ectasia, multiple ventral dural diverticula, erosion of lumbar vertebral bodies, adhesion of the nerve roots of the cauda equine, and the conus medullaris to the wall of the dural sac. Due to progressive clinical deterioration, surgical decompression was performed via laminoplasty with filum terminale resection to release adhesions involving the conus medullaris and nerve root. Postoperatively, constipation, urinary incontinence, and muscle strength improved. The possible mechanisms of CES associated with chronic AS are discussed.

Back pain, stiffness, uveitis, and peripheral arthritis are the main symptoms of ankylosing spondylitis (AS), a chronic inflammatory disease of the spondyloarthritis group that affects the spine and sacroiliac joints. Early identification is crucial since progressive illness can lead to spinal fusion and functional impairment. Even though AS and the human leukocyte antigen HLA-B27 are highly heritable, the pathophysiology of the disease cannot be entirely explained by genetic predisposition alone. A growing body of research identifies epigenetic pathways as important modulators connecting immunological dysregulation and HLA-B27-associated vulnerability. DNA methylation, histone modifications, and non-coding RNA expression are examples of epigenetic mechanisms that control tissue remodelling, immune cell differentiation, and the expression of inflammatory genes. Promoter hypermethylation is typically linked to gene suppression, while hypomethylation may allow gene activation, according to transcriptomic and epigenomic research, suggesting their potential as diagnostic indicators. Chromatin accessibility and disease-related gene expression are further influenced by histone modifications such as H3K9 acetylation. Combining genetic and epigenetic knowledge improves our understanding of the pathophysiology of AS and facilitates the development of improved diagnostic and treatment approaches.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with impaired quality of life and psychiatric comorbidities. Although depression has been widely studied in AS, the risk of anxiety disorders remains unclear. This study examined the long-term risk of anxiety disorders in patients with AS using a nationwide Korean cohort. Using the Korean National Health Insurance Service database (2012-2023), we identified patients newly diagnosed with ankylosing spondylitis (ICD-10 code M45) after applying a 3-year washout period to minimize inclusion of pre-existing cases. Patients with a prior history of anxiety disorders were excluded. Each case was propensity score-matched at a 1:10 ratio with controls by age, sex, and index year. The primary outcome was incident anxiety disorder (ICD-10 codes F40-F41). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. We analyzed 2,762 patients with AS and 27,620 controls over a mean follow-up of 4.02 years. The incidence rate of anxiety disorder was 27.38 per 1,000 person-years in AS and 18.91 in controls (IRR, 1.45; 95% CI, 1.28-1.63). AS was associated with a 40% higher risk of anxiety disorder (aHR, 1.40; 95% CI, 1.14-1.73), with the strongest association in females <60 years (aHR, 1.87; 95% CI, 1.52-2.30). AS increases the risk of anxiety disorders, particularly in younger females. Therefore, early psychiatric screening should be considered during AS management.

Background: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease frequently associated with hematological abnormalities such as anemia, thrombocytosis, and altered indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Anti-TNF therapy has revolutionized the treatment of AS, yet, the impact of anti-TNF therapy on hematological parameters in Iraqi patients remains underexplored. Objectives: to evaluate the effect of anti-TNF therapy on hematological parameters and disease activity in patients with AS at Merjan Teaching Hospital as well as documenting adherence, adverse events, and potential confounders. Methods: A prospective observational cohort study was conducted between January 2024 and July 2025, enrolling 85 biologic-naïve AS patients fulfilling modified New York or ASAS criteria. Patients received infliximab, adalimumab, or etanercept according to clinical judgment. Baseline and follow-up assessments included complete blood count (CBC), derived indices (NLR, PLR, SII), Erythrocyte Sedimentation Rate, c-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The statistical analyses were completed using paired t-tests, repeated measures ANOVA, correlation analysis and multivariate regression with adjustment for covariates. Results: The cohort comprised predominantly males (87%) with a mean age of 40.9 years. Baseline disease activity was high (mean BASDAI 6.26 ± 1.39; CRP 45.27 ± 44.61 mg/L; ESR 49.84 ± 15.28 mm/h). Anti-TNF therapy significantly reduced BASDAI, ASDAS, CRP, and ESR over 12 weeks. Hematological improvements included increased hemoglobin, reduced platelet counts, and normalization of NLR and PLR. Adherence exceeded 80%, with minor adverse events reported; no severe hematological toxicities occurred. Conclusions: Anti-TNF therapy in Iraqi AS patients effectively improved disease activity and corrected hematological abnormalities. Indices such as NLR and PLR may serve as reliable biomarkers of treatment response, underscoring the dual clinical and hematological benefits of biologic therapy in AS management.

This study aimed to examine the test-retest reliability and concurrent validity of the modified Four Square Step Test (mFSST) in individuals with ankylosing spondylitis (AS). Forty-eight participants diagnosed with AS were included. The mFSST was administered twice on the same day with a 1-h seated rest to assess reliability. Concurrent validity was tested with the Timed Up and Go (TUG), Five Times Sit-to-Stand (5xSTS), and Functional Reach (FR) tests, as well as disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis Functional Index (BASFI)) indices. Intraclass correlation coefficients (ICC), standard error of measurement (SEM), minimal detectable change (MDC95), Bland-Altman plots, and Spearman correlations were calculated. The mFSST demonstrated excellent test-retest reliability (ICC = 0.952), with SEM = 0.42s and MDC95 = 1.17s. Bland-Altman analysis showed narrow agreement limits (- 0.57 to + 1.31s). For validity, the mFSST correlated strongly with TUG (r = 0.771, p < 0.001) and moderately with 5xSTS (r = 0.473, p < 0.001), while no significant association was found with FR (p > 0.05). Retest values confirmed these results, showing strong correlation with TUG (r = 0.823, p < 0.001), moderate with 5xSTS (r = 0.606, p < 0.001), and a weak negative correlation with FR (r = - 0.334, p < 0.05). Furthermore, both mFSST test and retest scores showed moderate positive correlations with BASDAI (r = 0.501 and r = 0.543, respectively; p < 0.001) and BASFI (r = 0.605 and r = 0.681, respectively; p < 0.001). The mFSST is a reliable and valid tool for assessing dynamic balance in AS. Its brevity, minimal equipment needs, and interpretable error metrics support integration into clinical practice for baseline profiling and outcome monitoring. The MDC95 threshold offers clinicians a benchmark for interpreting meaningful change in rehabilitation. Key Points •The modified Four Square Step Test (mFSST) showed excellent test-retest reliability(ICC = 0.952) with a minimal detectable change of 1.17 s in individuals withankylosing spondylitis. •The mFSST demonstrated strong correlations with the Timed Up and Go test andmoderate correlations with the Five Times Sit-to-Stand test, BASDAI, and BASFI,supporting its concurrent validity. •The mFSST is a brief, equipment-free, and clinically useful tool for assessing andmonitoring dynamic balance and agility in ankylosing spondylitis.

Ankylosing spondylitis (AS) exhibits marked clinical heterogeneity that is poorly captured by conventional disease-centric analyses, hindering the development of personalized therapies. We propose a symptom-centered network pharmacology framework that directly links individual clinical symptoms to their underlying molecular mechanisms and therapeutic targets. AS- and symptom-associated genes were collected from GeneCards and prioritized using centrality analysis within protein-protein interaction networks. Symptom relevance was validated using patient-derived transcriptomic datasets. Network proximity between symptom modules and FDA-approved drug targets was assessed. A refined gene set, integrating TNF-associated neighbors and highly central nodes, was subjected to pathway enrichment analysis. Disease-centric analysis yielded a restricted 18-gene core enriched mainly in broad immune pathways. In contrast, the symptom-centered network identified 145 genes associated with specific symptoms such as inflammatory back pain and morning stiffness. Key genes, including PTEN, TLR4, JAK2, NRAS, and NR3C1, were significantly upregulated in AS patients. TNF showed local connectivity but limited global proximity, while IL17A- and JAK inhibitor-related targets were absent. A refined 24-gene module revealed enrichment in interleukin- and cytokine-mediated signaling pathways. Symptom-centered network analysis more effectively captures molecular heterogeneity in AS, providing a robust framework for symptom-specific target discovery and personalized therapeutic strategies.

Ankylosing spondylitis (AS) is an immune-mediated disease with an unknown etiology, posing challenges in effective treatment. This study aims to investigate the underlying mechanisms and explore the potential of traditional Chinese medicine (TCM) as a treatment avenue. Employing a multiomics analysis and leveraging public databases, we scrutinized AS immune cell subpopulations and associated genes. Gene regulatory mechanisms were dissected, and molecular docking was performed to assess the therapeutic efficacy of TCM. Our findings revealed a significant elevation in effector CD8+ memory T (Tem) cells in AS. Notably, the expression of STAT4 in this cell subpopulation was observed to be down-regulated. This down-regulation might be influenced by multiple circRNAs and miR-574-5p. Intriguingly, components derived from guava leaves exhibited a stable binding affinity to STAT4. Immunohistochemistry and qPCR results confirmed low expression of STAT4 in paraspinal ligament muscle tissue. This comprehensive multiomics analysis sheds light on potential underlying mechanisms of AS and underscores the prospect of traditional Chinese medicine as a viable therapeutic option. The study provides valuable insights for future research endeavors.

Ankylosing spondylitis (AS) significantly increases vulnerability to severe spinal injuries from minor trauma due to rigid "bamboo spine" morphology and secondary osteoporosis. Isolated intercostal artery rupture without rib fractures is extremely rare in general trauma populations. The concurrent occurrence of multilevel spinal fractures with complete spinal cord injury and occult intercostal artery hemorrhage following low-energy blunt trauma in AS patients has rarely been documented, and the underlying pathophysiological mechanisms remain unclear. A 43-year-old male with previously undiagnosed AS sustained a low-velocity bicycle collision, resulting in cervical and thoracic fracture-dislocation (C6-C7 and T11 bilateral laminae fractures) with complete spinal cord injury (ASIA Grade A, complete paraplegia), massive hemothorax, and active intercostal artery bleeding without significant rib fractures. Due to the patient's hemodynamic instability and altered consciousness on admission (hemorrhagic shock with SBP 63/40 mmHg), formal assessment of the bulbocavernosus reflex was not performed initially. The ASIA Grade A classification was based on complete absence of motor function (lower limbs 0/5) and sensory function below the T3 level, including absence of sacral sparing. Computed tomography angiography revealed active contrast extravasation from the right T10-level intercostal artery. Emergency transcatheter arterial angiography and embolization using coils and gelatin sponge particles successfully controlled the hemorrhage and stabilized the patient's hemodynamics. Following stabilization, staged posterior cervical (C5-C7) and thoracolumbar (T9-T12, L3-S1) pedicle screw-rod internal fixation with anterior cervical discectomy and fusion were performed. Despite postoperative complications including hospital-acquired pneumonia, pulmonary fungal infection (Candida albicans isolated from bronchoalveolar lavage, treated with intravenous fluconazole), and deep vein thrombosis, the patient demonstrated partial neurological recovery, with ASIA grade improving from Grade A (complete paraplegia) on admission to Grade C (incomplete paraplegia) at discharge on day 59. Serial neurological examinations documented the evolution from complete to incomplete injury (Table1). The patient was subsequently transferred to a specialized rehabilitation center for long-term functional training. This case illustrates the heightened and often unrecognized risk of complex, multisystem injuries in AS patients following seemingly minor trauma. Early recognition of hemothorax without rib fractures should raise high suspicion for intercostal artery injury, necessitating a lowered diagnostic threshold for computed tomography angiography. Transcatheter arterial embolization should be considered the first-line treatment for confirmed intercostal artery bleeding rather than a last resort. Prompt diagnosis, individualized multidisciplinary management, and early referral to specialized centers with interventional and spine surgical capabilities are essential for optimizing outcomes in these high-risk patients.

Human blood metabolites have been closely linked to ankylosing spondylitis (AS) in observational studies, yet direct causal evidence remains limited. This study aims to use Mendelian randomization (MR) to pinpoint causal metabolites associated with AS and to predict potential side effects of metabolite interventions. Genetic instruments for exposure were sourced from a genome-wide association study of 1400 blood metabolites, while genome-wide association study data for AS outcomes were derived from the FinnGen cohort. The primary MR analysis was conducted using the inverse variance weighted method. Supplemental analyses were conducted using weighted median, MR-Egger, simple mode, and weighted mode methods, while sensitivity analyses were performed to evaluate heterogeneity and pleiotropy. A replication analysis using an additional the UK Biobank cohort was also performed to determine metabolites associated with AS. The Steiger test and linkage disequilibrium score regression were used to further strengthen causal inference. Lastly, a phenome-wide Mendelian randomization analysis was performed to investigate the potential on-target side effects of metabolite interventions. After comprehensive analyses, 3 metabolites (the 2′-deoxyuridine levels, the hate to mannose ratio, and the Uridine to 2′-deoxyuridine ratio) were identified as being genetically associated with AS. The phenome-wide Mendelian randomization analysis revealed that the hate to mannose ratio might have deleterious effects on 4 other diseases, while no significant associations were found for the 2′-deoxyuridine levels or the uridine to 2′-deoxyuridine ratio with other diseases. This systematic MR analysis unveiled the potential role of the 2′-deoxyuridine levels, hate to mannose ratio and uridine to 2′-deoxyuridine ratio as the causal mediator in the development of AS. Considering the advantages and disadvantages, 2′-deoxyuridine appears as the most promising prospective therapeutic target for the prevention of AS.