-
Archives of Rheumatology Jun 2024The study aimed to evaluate the role of ultrasonographic assessment of enthesitis in patients with spondyloarthritis (SpA) in terms of disease activity, functionality,...
OBJECTIVES
The study aimed to evaluate the role of ultrasonographic assessment of enthesitis in patients with spondyloarthritis (SpA) in terms of disease activity, functionality, and quality of life.
PATIENTS AND METHODS
Ninety SpA patients (57 males, 33 females; mean age: 37.5±9.7 years; range, 18 to 60 years) were included in cross-sectional study between November 2016 and January 2017. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form-12 (SF-12), and Ankylosing Spondylitis Quality of Life (ASQoL) were utilized for clinical evaluation. The clinical evaluation of enthesitis was performed with the Spondyloarthritis Research Consortium of Canada (SPARCC) and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) via an algometer calibrated to 4 kg/cm of pressure. Ultrasound evaluation was performed according to Madrid Sonographic Enthesitis Index (MASEI). A total of 2,610 entheseal sites were examined clinically, and 1,080 were assessed ultrasonographically.
RESULTS
A significant proportion of enthesitis (463/1,080) was detected on ultrasonographic evaluation but not with clinical enthesitis score (MASES and SPARCC). Although ultrasonographic entheseal evaluation detected enthesitis in at least one enthesis of all patients, 35 of the patients had no enthesitis with clinical examination. The sites most frequently involved in the entheses were the proximal patellar tendon and Achilles tendon. The MASEI score did not correlate with the MASES, SPARCC, BASDAI, SF-12, and ASQoL but moderately correlated with the C-reactive protein (CRP) level (r=0.348), ASDAS-CRP (r=0.294), and BASFI score (r=0.244).
CONCLUSION
The association of ultrasonography scores with CRP levels and ASDAS-CRP indicates that ultrasonography is effective in detecting inflammation. The MASEI score weakly correlates with functionality but not with quality of life. Ultrasonographic evaluation is invaluable and merits to be incorporated into SpA disease scoring system.
PubMed: 38933722
DOI: 10.46497/ArchRheumatol.2024.10224 -
Archives of Rheumatology Jun 2024This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS).
OBJECTIVES
This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS).
PATIENTS AND METHODS
A total of 811 AS patients registered in the TURKBIO registry database between 2011 and 2019 were categorized according to their age at the time of entry into the registry and assigned to one of two groups: young patients, defined as <60 years of age (n=610), and those aged ≥60 years (n=201) were recorded as elderly patients. Demographic, clinical, and laboratory characteristics, along with disease activity markers and other follow-up parameters, as well as current and prior treatments, were electronically recorded during each visit using open-source software.
RESULTS
The mean age of the elderly patients was 67±5.8 years, while the mean age of the younger patients was 49.2±10.9 years. Male predominance was lower in the older AS group compared to the younger AS group (p=0.002). During follow-up period, 397 patients (comprising 318 young and 79 elderly individuals) had a history of using at least one biological disease-modifying agent (bDMARD). There was no significant difference between the groups in terms of DMARD and bDMARD-use distributions. First tumor necrosis factor inhibitor (TNFi) retention rates were found to be similar in both groups over 10 years of follow-up. Adverse events were found to be similar in young (19.9%) and elderly (26.8%) AS patients.
CONCLUSION
Research in the TURKBIO cohort reveals that both older and younger patients with AS exhibited similar disease activity levels with comparable treatment approaches. Moreover, the results of TNFi treatments in elderly patients were the same as those observed in younger patients, with no notable increase in safety concerns.
PubMed: 38933720
DOI: 10.46497/ArchRheumatol.2024.10391 -
International Journal of Rheumatic... Jun 2024Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to...
OBJECTIVE
Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively.
METHODS
Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma.
RESULTS
Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity.
CONCLUSION
Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.
Topics: Humans; Spondylitis, Ankylosing; Gastrointestinal Microbiome; Male; Antibodies, Monoclonal, Humanized; Female; Adult; Feces; Metabolomics; Treatment Outcome; RNA, Ribosomal, 16S; Case-Control Studies; Ribotyping; Middle Aged; Bacteria; Biomarkers; Predictive Value of Tests; Dysbiosis
PubMed: 38923187
DOI: 10.1111/1756-185X.15218 -
Rheumatology and Therapy Jun 2024A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other...
INTRODUCTION
A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab.
METHODS
Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI).
RESULTS
At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure.
CONCLUSIONS
Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.
PubMed: 38916823
DOI: 10.1007/s40744-024-00684-z -
BMC Musculoskeletal Disorders Jun 2024Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells...
BACKGROUND
Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells (PBMCs), plays an important role in the development of AS. Its expression is different between male and female. However, it is still unclear whether sex dimorphism of IL-17 contribute to sex differences in AS.
METHODS
GSE221786, GSE73754, GSE25101, GSE181364 and GSE205812 datasets were collected from the Gene Expression Omnibus (GEO) database. Differential expressed genes (DEGs) were analyzed with the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods. CIBERSORTx and EcoTyper algorithms were used for immune infiltration analyses. Machine learning based on the XGBoost algorithm model was used to identify the impact of DEGs. The Connectivity Map (CMAP) database was used as a drug discovery tool for exploring potential drugs based on the DEGs.
RESULTS
According to immune infiltration analyses, T cells accounted for the largest proportion of IL-17-secreting PBMCs, and KEGG analyses suggested an enhanced activation of mast cells among male AS patients, whereas the expression of TNF was higher in female AS patients. Other signaling pathways, including those involving metastasis-associated 1 family member 3 (MAT3) or proteasome, were found to be more activated in male AS patients. Regarding metabolic patterns, oxidative phosphorylation pathways and lipid oxidation were significantly upregulated in male AS patients. In XGBoost algorithm model, DEGs including METRN and TMC4 played important roles in the disease process. we integrated the CMAP database for systematic analyses of polypharmacology and drug repurposing, which indicated that atorvastatin, famciclocir, ATN-161 and taselisib may be applicable to the treatment of AS.
CONCLUSIONS
We analyzed the sex dimorphism of IL-17-secreting PBMCs in AS. The results showed that mast cell activation was stronger in males, while the expression of TNF was higher in females. In addition, through machine learning and the CMAP database, we found that genes such as METRN and TMC4 may promote the development of AS, and drugs such as atorvastatin potentially could be used for AS treatment.
Topics: Humans; Female; Male; Interleukin-17; Spondylitis, Ankylosing; Machine Learning; Leukocytes, Mononuclear; Sex Characteristics; Computational Biology; Databases, Genetic; Gene Expression Profiling
PubMed: 38914997
DOI: 10.1186/s12891-024-07589-6 -
Rheumatology International Jun 2024Ankylosing spondylitis is chronic progressive disease, which decrease functions of musculoskeletal system including chest area. Those changes influences respiratory...
INTRODUCTION
Ankylosing spondylitis is chronic progressive disease, which decrease functions of musculoskeletal system including chest area. Those changes influences respiratory mechanics, worsen conditions of proper ventilation of lungs.
OBJECTIVES
Rating of functional and respiratory parameters and dependence between them at patients with ankylosing spondylitis.
MATERIALS & METHODS
The study included 45 patients with diagnosed ankylosing spondylitis. Chest and upper limbs mobility, resting spinal curvature alignment were assessed, and respiratory parameters were measured in a plethysmographic chamber JAGGER MasterScreen Body.
RESULTS
Ankylosing spondylitis patients had lower respiratory parameters especially sReff, and FRC. Restriction of chest and upper limbs mobility was also demonstrated. Forward head extension was observed based on the occipital wall test. Correlations between functional parameters and correlations between functional and respiratory parameters were shown, in particular MIP, MEP, sReff, Rtot, TLC, ERV.
CONCLUSIONS
The study confirmed a decrease in functional and respiratory parameters in the examined patients with ankylosing spondylitis compared to the applicable standards. A significant relationship was found between functional parameters in the upper body and respiratory parameters, which worsen with increasing thoracic dysfunction. The obtained results indicate the directions of therapy that should be taken into account to improve respiratory parameters and reduce respiratory dysfunction in these patients. Chest-focused physiotherapy appears to be an important element in improving function in patients with ankylosing spondylitis.
PubMed: 38914771
DOI: 10.1007/s00296-024-05642-0 -
Iranian Journal of Immunology : IJI Jun 2024Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1)...
BACKGROUND
Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of autoimmune diseases such as AS pathogenesis.
OBJECTIVE
To investigate PD-1 gene expression and its epigenetic regulation by detecting methylated CpG islands in the regulatory sites of the gene. This will provide insight into the mechanisms involved in the disease.
METHODS
30 AS patients and 30 healthy individuals were examined to detect the 16 CpG islands in intron 1 using bisulfite conversion and methylation-specific PCR technique. In addition, RNA samples were isolated from fresh peripheral blood mononuclear cells (PBMCs), and after complementary DNA (cDNA) synthesis, the expression level of the PD-1 gene was evaluated using Real-Time PCR.
RESULTS
The CpG islands located in the intronic zone of the PD-1 gene were hyper-methylated in both the patients with AS and the healthy controls. The gene expression of PD-1 was significantly downregulated in AS patients compared with the controls (p=0.017). A negative correlation between the Bath Ankylosing Spondylitis Disease Activity Index and PD-1 gene expression was also revealed.
CONCLUSION
The low level of PD-1 gene expression is implicated in the pathogenesis of AS. However, in both groups, the methylation level of the intron 1 CpG islands of the PD-1 gene suggests that other regulatory mechanisms are more relevant to PD-1 gene expression than methylation in the intron.
PubMed: 38912647
DOI: 10.22034/iji.2024.101565.2757 -
Talanta Jun 2024Ankylosing spondylitis (AS), Osteoarthritis (OA), and Sjögren's syndrome (SS) are three prevalent autoimmune diseases. If left untreated, which can lead to severe joint...
BACKGROUND
Ankylosing spondylitis (AS), Osteoarthritis (OA), and Sjögren's syndrome (SS) are three prevalent autoimmune diseases. If left untreated, which can lead to severe joint damage and greatly limit mobility. Once the disease worsens, patients may face the risk of long-term disability, and in severe cases, even life-threatening consequences.
RESULT
In this study, the Raman spectral data of AS, OA, and SS are analyzed to auxiliary disease diagnosis. For the first time, the Euclidean distance(ED) upscaling technique was used for the conversation from one-dimensional(1D) disease spectral data to two-dimensional(2D) spectral images. A dual-attention mechanism network was then constructed to analyze these two-dimensional spectral maps for disease diagnosis. The results demonstrate that the dual-attention mechanism network achieves a diagnostic accuracy of 100 % when analyzing 2D ED spectrograms. Furthermore, a comparison and analysis with s-transforms(ST), short-time fourier transforms(STFT), recurrence maps(RP), markov transform field(MTF), and Gramian angle fields(GAF) highlight the significant advantage of the proposed method, as it significantly shortens the conversion time while supporting disease-assisted diagnosis. Mutual information(MI) was utilized for the first time to validate the 2D Raman spectrograms generated, including ED, ST, STFT, RP, MTF, and GAF spectrograms. This allowed for evaluation of the similarity between the original 1D spectral data and the generated 2D spectrograms.
SIGNIFICANT
The results indicate that utilizing ED to transform 1D spectral data into 2D images, coupled with the application of convolutional neural network(CNN) for analyzing 2D ED Raman spectrograms, holds great promise as a valuable tool in assisting disease diagnosis. The research demonstrated that the 2D spectrogram created with ED closely resembles the original 1D spectral data. This indicates that ED effectively captures key features and important information from the original data, providing a strong descript.
PubMed: 38908135
DOI: 10.1016/j.talanta.2024.126426 -
European Journal of Dermatology : EJD Apr 2024Previous studies reveal that psoriatic arthritis (PsA) and ankylosing spondylitis (AS) share susceptibility genes, such as HLA-B27, demonstrating a degree of genetic...
Previous studies reveal that psoriatic arthritis (PsA) and ankylosing spondylitis (AS) share susceptibility genes, such as HLA-B27, demonstrating a degree of genetic overlap between these diseases. Recent studies have identified a number of novel AS and PsA genetic susceptibility loci, but data on these loci in Chinese PsA patients are limited. To identify candidate genes that confer susceptibility to PsA in Chinese patients with PsA, psoriasis vulgaris (PsV), and healthy controls. Sixteen susceptibility loci, reported in a genome-wide association study of AS, and nine susceptibility loci, reported in candidate gene studies of PsA, were examined. Single-nucleotide polymorphisms (SNPs) were genotyped in 503 patients with PsA, 496 patients with PsV, and 979 healthy controls using the SNPscanTM multiplex SNP genotyping platform. PLINK software and logistic regression analysis were used to estimate the statistical significance of associations. PPP2R3C (rs8006884) was shown to significantly associate with PsA+PsV (p = 1.92×10-3, OR = 1.28) and was suggested to associate with PsV (p = 0.03, OR = 1.19). A suggestive association was also observed between IL-23R (rs12141575) and PsA as well as with axial PsA based on subtype analysis, KIF3A (rs2897442) and PsV, and ERN1 (rs196941) or IFIH1 (rs984971) and axial PsA. Our results suggest that PPP2R3C confers susceptibility to PsA and PsV, and that this gene may be related to the pathogenesis of psoriatic lesions and arthritis. Moreover, our results indicate a possible association between IL-23R, ERN1, or IFIH1 and subtypes of PsA, and between KIF3A and PsV.
Topics: Humans; Arthritis, Psoriatic; Spondylitis, Ankylosing; Male; Polymorphism, Single Nucleotide; Female; Genetic Predisposition to Disease; Asian People; Adult; Middle Aged; Case-Control Studies; China; Receptors, Interleukin; Protein Phosphatase 2; Genotype; Genome-Wide Association Study; Psoriasis; East Asian People
PubMed: 38907550
DOI: 10.1684/ejd.2024.4641 -
Scientific Reports Jun 2024Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate...
Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe.
Topics: Humans; Spondylitis, Ankylosing; Male; Female; Middle Aged; Registries; Adult; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Age of Onset; Antirheumatic Agents; Tumor Necrosis Factor-alpha
PubMed: 38902436
DOI: 10.1038/s41598-024-65180-4