Impact of inflammation and anti-inflammatory therapies on the incidence of major cardiovascular events in patients with ankylosing spondylitis: A population-based study.

OBJECTIVE: To examine the independent effect of inflammatory burden and various treatments on the risk of incident major adverse cardiovascular events (MACE) in ankylosing spondylitis (AS) patients. METHODS: AS patients were retrospectively selected from a territory-wide database between 2006 and 2015, and were followed until the end of 2018. The primary outcome was the first occurrence of MACE. Multivariate time-varying Cox proportional hazard models were used to determine the associations between inflammatory burden (measured by c-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and different therapies with incident MACE, after adjusting for traditional cardiovascular (CV) risk factors. RESULTS: A total of 3827 patients with AS (mean age: 45.2 ± 15.0 years, male: 2911 [76.1 %]) were recruited. After a follow-up of 23,275 person-years, 135 patients (3.5 %) developed a first MACE. Univariate analyses showed that elevated ESR and CRP levels, and the use of glucocorticoids were associated with a significantly higher risk of MACE, while the use of sulfasalazine (SLZ), biologic DMARDs and non-cyclooxygenase-2 inhibitors (non-COX-IIi) were associated with reduced risk of MACE. After adjusting for CV risk factors in the multivariable models, only ESR (HR: 1.02; ESR ≥30 mm/h, HR:1.94) and CRP level (HR: 1.14; CRP >3 mg/dl HR:5.43) remained significantly associated with increased risk of MACE, while SLZ use (HR: 0.41-0.52) was protective against MACE. CONCLUSION: High inflammatory burden was an independent predictor associated with an increased risk of MACE, while the use of SLZ might reduce risk of incident MACE in patients with AS.

Sex dimorphism of IL-17-secreting peripheral blood mononuclear cells in ankylosing spondylitis based on bioinformatics analysis and machine learning.

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.

Combined analysis of metabolomics and 16S rRNA sequencing for ankylosing spondylitis patients before and after secukinumab therapy.

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.

Navigating the Factors Affecting Functional Impairment in Spondyloarthritis.

Objectives: This study aimed to assess the predictive factors of functional impairment in spondyloarthritis (SpA) patients assessed with bath ankylosing spondylitis functional index (BASFI) and Lequesne Index (LI). Methods: This retrospective study was conducted at the Rheumatology Department of Mohamed Kassab Institute of Orthopedics, Manubah, Tunisia, and collected data from 2008 to 2019 over a period of 4 months (August to November 2019). Socio-demographic and disease-related data of SpA patients were collected. Disease activity was assessed using the bath ankylosing spondylitis-global score (BASG-s) and the bath ankylosing spondylitis disease activity index (BASDAI). The spinal mobility was evaluated by the bath ankylosing spondylitis metrology index (BASMI). Structural progression was evaluated with the bath ankylosing spondylitis radiologic index (BASRI) and modified stoke ankylosing spondylitis spine score (mSASSS). A multivariate analysis was done to search for predictive factors associated with BASFI and LI. Results: A total of 263 patients were included. The mean age was 38.9 ± 12.7 years and the gender ratio was 2.7. The mean age of onset of SpA was 27.6 ± 10.8 years and disease duration was 11.3 ± 9.5 years. Occupation was significantly associated with BASFI and LI scores. A significant functional impact was notably correlated with a long duration of the disease. The two scores were correlated with a limitation of spinal mobility (BASMI), a greater disease activity (BASDAI and erythrocyte sedimentation rate) and a greater impact of the disease on health status (BASG-s). Significant functional impairment was also correlated with structural impairment (mSASSS, BASRI and sacroiliitis grade). The variables independently related to BASFI were the mSASSS score and the BASDAI. The variables independently related to LI were profession (unemployed subjects had higher scores), the mSASSS score and the BASMI. Conclusion: Occupation, disease activity, mobility and structural progression predicted functional impairment in Tunisian SpA patients.

Impact of a Patient Support Program on time to discontinuation of adalimumab in Australian adult patients with immune-mediated inflammatory diseases-an observational study.

This observational study evaluated the impact of a sponsor company-provided Patient Support Program (PSP) on discontinuation of adalimumab in adult Australian patients eligible for Pharmaceutical Benefit Scheme (PBS)-reimbursed adalimumab for Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Crohn's Disease (CD), Ulcerative Colitis (UC), or Hidradenitis Suppurativa (HS). Patients initiating adalimumab between May 2018 and September 2019 were enrolled into two prospective cohorts based on their decision to opt for or decline the PSP (PSP or non-PSP cohorts). In addition, a historical, retrospective Non-PSP cohort was established from the Services Australia 10% PBS dataset by extracting data of patients initiating adalimumab prior to the introduction of adalimumab PSPs and based on adalimumab PBS listing dates (AS: April 2007 to March 2009; PsA/RA: January 2007 to December 2008; CD: January 2009 to December 2010; HS and UC indications not included). Follow-up for all cohorts was 12 months. The primary endpoint was the time to discontinuation, compared between the prospective PSP cohort and the prospective or retrospective Non-PSP cohort. Inverse probability of treatment weighting was used to balance the cohorts. A Cox proportional hazards model indicated no difference in time to discontinuation between the prospective PSP (n = 162) and non-PSP (n = 65) cohorts (HR [95% CI] = 1.256 [0.616-2.563], p = 0.5304). The 12-month adalimumab persistence rates (95% CI) were 78% (69%, 84%) and 82% (67%, 90%), respectively. In contrast, discontinuation was less likely in the prospective PSP (n = 151) compared with the retrospective non-PSP (n = 297) cohort (HR [95% CI] = 0.44 [0.28-0.68], p<0.001). The 12-month persistence rates (95% CI) were 81% (76%, 90%) and 61% (56%, 67%), respectively. Overall, this study suggests that optimal adalimumab persistence can be achieved with either a structured PSP or healthcare support from other sources, but this was not the case more than a decade ago.

Exploring the Pathogenesis of Spondylarthritis beyond HLA-B27: A Descriptive Review.

Spondylarthritis (SpA) is a chronic inflammatory condition that encompasses damage to the axial or peripheral skeleton, accompanied by specific extra-articular symptoms. Within this group, Ankylosing Spondylitis stands out as the hallmark member. Although the heritability of Ankylosing Spondylitis is estimated to be over 95%, only a portion of the heritability has been explained, with HLA-B27 accounting for 20.1% of it; therefore, ongoing research endeavors are currently concentrated on investigating the potential participation of different entities in the development of the disease. Genome-wide association studies have led to significant advances in our understanding of the genetics of SpA. In this descriptive review, we delve into the pathogenesis of Spondylarthritis beyond HLA-B27. We summarize the latest research on the potential participation of various entities in the development of the disease, including other genetic loci, immune dysregulation, microbiota, and environmental factors. The multifactorial nature of SpA and the complex interplay of genetic, immunological, and environmental factors are being increasingly recognized; therefore, it is of paramount importance to consider a holistic approach to comprehend the pathogenesis of SpA in order to identify novel therapeutic targets.

Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.

Genetic overlap between psoriatic arthritis and ankylosing spondylitis in a Chinese population.

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.

Assessing safety and efficacy of TNFi treatment in late onset ankylosing spondylitis: a TURKBIO registry study.

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.

Inflammation in the posterior elements, in particular the facet joint and facet joint ankylosis over 2-year follow-up in radiographic axial spondyloarthritis.

OBJECTIVES: To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial spondyloarthritis (r-axSpA). METHODS: Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort, inclusion criteria r-axSpA and ≥1 radiographic spinal syndesmophyte, were studied. MRI of the full spinal was performed at baseline, 1 and 2 years. PE/FJ inflammatory lesions and FJA were assessed per vertebral unit (VU) level by three readers. With multilevel time-lagged autoregressive generalised estimated equations, the association between PE/FJ inflammation and the subsequent development of FJA was investigated, taking the reader and VU levels into account. RESULTS: Out of the 58 patients with at least 2 reader scores available, mean age 49 (SD 10) years, 84% men, 59% had baseline PE inflammation, 24% had FJ inflammation and 26% had FJA. PE inflammation was more prevalent in the lower thoracic spine and FJ inflammation in the upper thoracic spine. VU with PE or FJ inflammation showed subsequent new FJA in two and one VU levels, respectively. The probability of developing FJA doubled with prior FJ inflammation. In multilevel analysis, FJ inflammation was associated with subsequent FJA (OR=3.8, 95% CI: 1.5 to 9.8), while no association was found between PE inflammation and new FJA (OR=1.2 (0.6-2.4)). CONCLUSIONS: FJ inflammation is rare in severe r-axSpA, but when present, the likelihood of developing subsequent FJA is over three times higher compared with FJ without inflammation. This finding contributes to the understanding of the relationship between inflammation and ankylosis at the same anatomical location in patients with axSpA.

Exploration of the combined role of immune checkpoints and immune cells in the diagnosis and treatment of ankylosing spondylitis: a preliminary study immune checkpoints in ankylosing spondylitis.

OBJECTIVE: Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. METHODS: Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). RESULTS: HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. CONCLUSION: Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.

Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.

Background: Ankylosing spondylitis (AS) is a complex condition with a significant genetic component. This study explored circulating proteins as potential genetic drug targets or biomarkers to prevent AS, addressing the need for innovative and safe treatments. Methods: We analyzed extensive data from protein quantitative trait loci (pQTLs) with up to 1,949 instrumental variables (IVs) and selected the top single-nucleotide polymorphism (SNP) associated with AS risk. Utilizing a two-sample Mendelian randomization (MR) approach, we assessed the causal relationships between identified proteins and AS risk. Colocalization analysis, functional enrichment, and construction of protein-protein interaction networks further supported these findings. We utilized phenome-wide MR (phenMR) analysis for broader validation and repurposing of drugs targeting these proteins. The Drug-Gene Interaction database (DGIdb) was employed to corroborate drug associations with potential therapeutic targets. Additionally, molecular docking (MD) techniques were applied to evaluate the interaction between target protein and four potential AS drugs identified from the DGIdb. Results: Our analysis identified 1,654 plasma proteins linked to AS, with 868 up-regulated and 786 down-regulated. 18 proteins (AGER, AIF1, ATF6B, C4A, CFB, CLIC1, COL11A2, ERAP1, HLA-DQA2, HSPA1L, IL23R, LILRB3, MAPK14, MICA, MICB, MPIG6B, TNXB, and VARS1) that show promise as therapeutic targets for AS or biomarkers, especially MAPK14, supported by evidence of colocalization. PhenMR analysis linked these proteins to AS and other diseases, while DGIdb analysis identified potential drugs related to MAPK14. MD analysis indicated strong binding affinities between MAPK14 and four potential AS drugs, suggesting effective target-drug interactions. Conclusion: This study underscores the utility of MR analysis in AS research for identifying biomarkers and therapeutic drug targets. The involvement of Th17 cell differentiation-related proteins in AS pathogenesis is particularly notable. Clinical validation and further investigation are essential for future applications.

[Hypogonadism in men with inflammatory joint diseases: Frequency and clinical characteristics].

AIM: To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact of HG on the course of RA and and concomitant diseases. MATERIALS AND METHODS: A single-stage continuous study included 170 men with RA, 57 men with AS and 85 men with PsA, who were hospitalized at the Nasonova Research Institute of Rheumatology. Patients were assessed for total testosterone (ТS) levels and subsequently divided into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of rheumatic disease, as well as on concomitant conditions. The second stage of the study involved a pairwise intergroup comparison among patients with HG with RA, AS and PsA. RESULTS: The incidence of ТS deficiency among patients with RA was 24.1%, among patients with AS - 17.5%, and with PsA - 31.8%. In patients with RA, HG was associated with a significantly higher mean body mass index, higher fasting blood glucose and uric acid, higher erythrocyte sedimentation rate and anemia. Patients with AS with HG had significantly lower hemoglobin levels and more frequent anemia, as well as higher levels of C-reactive protein and erythrocyte sedimentation rate. In PsA, older age was observed in the androgen deficiency group, as well as higher body mass index and fasting glucose levels; obesity was more common. An intergroup comparison of quantitative and qualitative indicators between patients with androgen deficiency in all three rheumatic diseases (RDs) did not reveal significant differences in the average concentrations of ТS, luteinizing hormone, sex hormone binding globulin, experience of RD, laboratory markers of inflammatory activity, as well as glucose and uric acid. A similar incidence of diabetes mellitus, obesity and anemia was noted for all three nosologies. CONCLUSION: ТS levels and the presence of HG were not associated with the stage and activity of RD, but ТS deficiency was accompanied by higher laboratory indicators of inflammatory activity, lower hemoglobin values, and metabolic disorders. Patients with HG, regardless of nosology, had similar levels of sex hormones and indicators reflecting RD and concomitant conditions.

[Current treatment for spondyloarthritis: focus on netakimab. A review].

Spondyloarthritis (SpA) is a group of rheumatic diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA) and a number of other diseases. SpA lead to a significant social problem, since it is a common pathology that debuts mainly at a young age, significantly impairing the ability to work and the ability to social contacts of the most active part of the population. For all the main types of chronic progressive SpA, biological agents (biologics) are of great importance in patients with persistent activity despite standard treatment, especially in the case of predominantly axial involvement, since in this case it is actually the only option for effective treatment, in addition to the constant use of non-steroidal anti-inflammatory drugs (NSAIDs). Over the past decade, interleukin-17A (IL-17A) inhibitors have taken the first place in therapy of SpA, because, according to modern ideas about pathogenesis, IL-17A may be a key target for therapeutic intervention in SpA. In terms of ensuring availability for Russian patients with SpA, it is of particular importance to the introduction of the original medication from the group of IL-17A inhibitors Netakimab (NTK). This review presents data from randomized clinical trials of NTK phases I, II and III in AS and PsA also post-registration observational studies of phase IV, including analysis of subpopulations of patients of special interest, in particular, patients with psoriatic spondylitis. NTK demonstrated high effectiveness in the treatment of SpA both in randomized clinical trials and in clinical practice. The drug is characterized by a rapid onset of clinical action and persistent maintenance of the achieved improvement, a complex effect on various manifestations of the disease, is able to have a structure-modifying effect and slow down the progression of both the erosive process and osteoproliferation. The safety profile of NTK is generally typical for the entire group of IL-17 inhibitors. The drug has low immunogenicity, which allows us to count on the possibility of many years of effective use. Resolutions of expert councils on the use of NTK in AS and PsA support the inclusion of this drug in clinical guidelines.

Comparison of Yoga with exercise in ankylosing spondylitis on mobility and functional capacity.

AIM: To compare the effects of Yoga with traditional exercise on the mobility and functional capacity of individuals with ankylosing spondylitis (AS). METHODS: The participants of the study were recruited at the rheumatology department, adhering to the study's inclusion and exclusion criteria. Participants were randomized into two groups (Group A - Yoga, and Group B - exercise).The candidates participated in an 8-week intervention consisting of 3 weekly sessions of either Yoga or Exercise intervention. Outcomes were collected at pre-treatment, at 8 weeks, and at 12 weeks. RESULTS: The within-group comparison showed an improvement in all outcome measures with p < .05 between post-treatment and the follow-up. In the yoga group, there was an improvement in the measures of BASMI (p = .001), BASFI (p = .005), PSQI (p = .021), CE (p = .053) and NPRS (p = .001). Similarly, in the exercise group, there was an improvement in BASMI (p = .002), BASFI (p = .003), PSQI (p = .010), CE (p = .004) and NPRS (p = .001). In the between group comparison at post-treatment, there were no statistically significant differences in BASMI (yoga = 3.0 ± 1.50, exercise = 2.3 ± 1.38), PSQI (yoga = 5.3 ± 1.50, exercise = 4.9 ± 1.17) and NPRS (yoga = 1.3 ± 2.22, exercise = 0.4 ± 0.50) CE (yoga = 4.0 ± 1.18, exercise = 3.4 ± 0.96), BASFI (yoga = 1.8 ± 2.14, exercise = 2.1 ± 1.87). CONCLUSION: The results demonstrated a statistically significant improvement in within-group scores of mobility, functional capacity, sleep quality and pain in AS patients of both intervention programs but there were no significant differences between the groups.

Effectiveness of exercise intervention in relieving symptoms of ankylosing spondylitis: A network meta-analysis.

BACKGROUND: Ankylosing spondylitis(AS) is a chronic inflammatory rheumatic disease that leads to a reduced quality of life. Exercise appears to be one of the promising modes of intervention. The aim of this study was to review the available evidence and compare the effectiveness of different exercises in relieving symptoms of AS. METHODS: We searched the Pubmed, WOS, EMbase, CNKI, Cochrane Library, and Scopus databases. The search has spanned from the creation of the database until September 15, 2023. We extracted the first author, year of article publication, sample information, intervention, duration of intervention, and outcome indicators from the literature that met the inclusion criteria. The Cochrane Risk Assessment Tool was used to assess the risk of bias for included studies. I² was used to judge the consistency of the included studies. Egger's test and Begg's test were used to judge whether there was significant publication bias. Forest plots were used to compare intervention effects and SUCRA was provided to rank the effects of the interventions. This study has been registered in PROSPERO(No. CRD42024518522). RESULTS: After screening, 10 papers matched the inclusion criteria for this study, and the total sample size of the 10 papers was 623. Upon analysis, the papers included in this study did not have significant publication bias (Begg's Test P = 0.210) and had good consistency (P>0.05). The direct comparisons showed that Running, Pilates, Stretching, Yoga, and Tai Chi were more effective interventions than traditional therapies. The effect sizes, confidence intervals, and number of studies for each intervention are shown below: Running [MD -1.90 (95% CI -3.14,-0.66) n = 1], Pilates [MD -1.70 (95% CI -2.90,-0.51) n = 1], Stretching [MD -1.54 (95% CI -2.21,-0.88) n = 4], Yoga [MD -1.24 (95% CI -2.18,-0.30) n = 1], Tai Chi [MD -0.78 (95% CI -1.44,-0.12) n = 2], Exergame[MD -0.80 (95% CI -1.99,0.39) n = 1], Swiss balls[MD -1.07 (95% CI -2.58,0.44) n = 1]. The indirect comparisons showed that the range of effect sizes for each sport intervention intersected the null line. Based on cumulative probability, the order of effectiveness of different exercises in relieving AS symptoms is Running, Pilates, Stretching, Yoga, Tai Chi, Exergame, and Swiss ball. CONCLUSION: Running, Pilates, Stretching, Yoga, and Tai Chi provided significant relief from AS symptoms. Exergame and Swiss ball were not statistically significant in relieving AS symptoms. There were no significant differences in the effectiveness of different exercise interventions in relieving AS symptoms. Running may have the most beneficial effect on alleviating AS symptoms.

Comparative study of two laboratory techniques for the detection of HLA-B27 in patients with axial spondyloarthritis: a cross-sectional analysis.

BACKGROUND: The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. METHODS: An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele's presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant. RESULTS: Of the participants, 90.3% (n = 56) were HLA-B27 positive according to FC, while 79% (n = 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived. CONCLUSIONS: FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.

A short review on deciphering Vyadhikshamatva: insights from HLA-B27-ankylosing spondylitis relation.

OBJECTIVES: Various aspects of the concept of Vyadhikshamatva have been thoroughly explored, highlighting its profound significance in resisting disease manifestation, particularly in the context of Ankylosing spondylitis. Investigated the relationship between HLA-B27 and Ankylosing spondylitis (AS) by examining current knowledge and hypotheses Furthermore, efforts were made to portray the influence of prakruti (constitution) and balam (strength) on disease manifestation and progression. METHODS: Ayurvedic literature along with contemporary research works was analyzed for correlating various aspects like vyadhikshamatva,oja (The final essence of all body elements), and balam along with their influence on the defensive mechanism of the body. A thorough literature search was conducted to explore the strong association between HLA-B27 and AS by examining various hypotheses like the Arthritogenic peptide hypothesis, the Misfolding hypothesis, the Surface Homodimer hypothesis, and the ß2 microglobulin hypothesis that attempts to explain the pathogenic role of HLA-B27 in AS. Alongside classical Ayurvedic texts, databases like PubMed and Scopus were searched using keywords such as Immunity, Ankylosing spondylitis, Vyadhikshamatva, HLA-B27, Balam, and Autoimmune disorder with the help of Boolean operators. RESULTS: The review highlighted the critical role of Vyadhikshamatva in disease prevention, particularly in influencing the manifestation of conditions like AS despite genetic predisposition (HLA-B27). Further, the understanding of the Ayurvedic concepts can clearly explain the conflict that has arisen in the determination of the positive HLAB27 gene in Ankylosing Spondylitis as a definite diagnosing criteria. CONCLUSIONS: This comprehensive understanding will uplift the need for personalized medicine in disease management. Further research must be needed to understand the interaction between genetic factors (HLAb27), individual constitution, and their vyadikshamatva.

scRNA + TCR-seq revealed the dual TCR pTh17 and Treg T cells involvement in autoimmune response in ankylosing spondylitis.

OBJECTIVE: Th17 and Treg play important roles in AS, but their single and dual TCR pairing types, ratios, and CDR3 characteristics remain unknown. METHODS: Single-cell RNA + TCR-seq results from six AS patients were used to cluster T-cell subpopulations and analyze the single and dual TCR T cell ratio, diversity/clonality/overlap of CDR3, and expression of transcription factors. RESULTS: 1. AS patients have about 10% of dual TCR T cells, and SFMC have decreased diversity CDR3 libraries and significant clonal proliferation compared to PBMC. 2. Dual TCR ratio: memory T > naive T; pTh 17 > Th17; Treg /Th17/Th1/EM significantly higher than naive CD4 + T/CM, Pathogenic Th17 cells contain clonally proliferating single TCR and dual TCR cells. 3. The expression of single TCR and dual TCR transcription factors of each T cell subpopulation was basically the same, but there was differential expression of characteristic transcription factors, e.g. Foxp3, CTLA4, STAT5B, IL10RB, LAG3 in dual TCR Treg was higher than that of single TCR Treg; TNFSF10/12, TNFRSF4/14, CCL5, KLRB1 in dual TCR pTh17 were significantly higher than those in single TCR pTh17. 4. Between naive CD4 + T, pTh17, Th1 and Treg, there are partially identity identical tcr paired cells. CONCLUSIONS: The high proportion of dual TCR T cells such as pTh17 and Treg in AS and the high expression of some transcription factors suggested a close association with self-response in AS; The overlap of CDR3 between Th1, Th17,pTh17, and Treg in AS suggested that the subpopulations may be differentiated from each other to regulate the inflammatory homeostasis and progression.

Association between inflammatory joint disease and severe or treatment-resistant depression: population-based cohort and case-control studies in Sweden.

OBJECTIVE: To investigate whether the association between depression and inflammatory joint disease (IJD; rheumatoid arthritis [RA], psoriatic arthritis [PsA], ankylosing spondylitis/spondyloarthropathies [AS], and juvenile idiopathic arthritis [JIA]) is affected by the severity or treatment-resistance of depression. METHOD: Parallel cohort studies and case-control studies among 600,404 patients with a depressive episode identified in Swedish nationwide administrative registers. Prospective and retrospective risk for IJD in patients with depression was compared to matched population comparators, and the same associations were investigated in severe or treatment-resistant depression. Analyses were adjusted for comorbidities and sociodemographic covariates. RESULTS: Patients with depression had an increased risk for later IJD compared to population comparators (adjusted hazard ratio (aHR) for any IJD 1.34 [95% CI 1.30-1.39]; for RA 1.27 [1.15-1.41]; PsA 1.45 [1.29-1.63]; AS 1.32 [1.15-1.52]). In case-control studies, patients with depression more frequently had a history of IJD compared to population controls (adjusted odds ratio (aOR) for any IJD 1.43 [1.37-1.50]; RA 1.39 [1.29-1.49]; PsA 1.59 [1.46-1.73]; AS 1.49 [1.36-1.64]; JIA 1.52 [1.35-1.71]). These associations were not significantly different for severe depression or TRD. CONCLUSION: IJD and depression are bidirectionally associated, but this association does not seem to be influenced by the severity or treatment resistance of depression.