Identifying prioritization of therapeutic targets for ankylosing spondylitis: a multi-omics Mendelian randomization study.

Background: To investigate the associations of methylation, expression, and protein quantitative trait loci (mQTL, eQTL, and pQTL) with ankylosing spondylitis (AS) and find out genetically supported drug targets for AS.

Methods: The summary-data-based Mendelian randomization (SMR) and Bayesian co-localization analysis were used to assess the potential causality between AS and relevant genes. The GWAS data obtained from the International Genetics of Ankylosing Spondylitis Consortium (IGAS) were set as the discovery stage, and the FinnGen and UK Biobank databases were used to replicate the analysis as an external validation.

Evaluating methods for integrating single-cell data and genetics to understand inflammatory disease complexity.

Background: Understanding genetic underpinnings of immune-mediated inflammatory diseases is crucial to improve treatments. Single-cell RNA sequencing (scRNA-seq) identifies cell states expanded in disease, but often overlooks genetic causality due to cost and small genotyping cohorts. Conversely, large genome-wide association studies (GWAS) are commonly accessible.

Axial involvement in psoriatic arthritis: is it unique?

Axial involvement in psoriatic arthritis (PsA) has been a major feature of the disease since the original description by Wright and Moll. However, despite over 50 years of study, there is still no accepted definition of axial PsA, nor validated classification criteria. Numerous observational studies have described a phenotype of axial involvement that differs from classical ankylosing spondylitis (AS or axial spondyloarthritis) both clinically and radiographically, and in the frequency of the HLA-B27 antigen.

Assessment of clinical benefit, cost and uptake of biosimilars versus reference biologics in immune-mediated inflammatory diseases in China.

Background: As China is one of the countries with the highest recorded cases of Immune-Mediated Inflammatory Diseases (IMIDs), these diseases have also emerged as a serious public health concern. Biosimilars, potentially lower-cost versions of biologics, may improve access to more affordable yet comparably effective treatments. Encouragingly, China launched its abbreviated biosimilar pathway in 2015, and since then, a large number of biosimilars have been approved.

Investigating the causal relationship between immune factors and ankylosing spondylitis: insights from a Mendelian Randomization study.

Background: Despite previous studies indicating a close relationship between immune system and ankylosing spondylitis (AS), the causal relationship between them remains unclear.

Methods: Genome-wide association data were utilized to explore the causal link between 731 immune cells and AS using a bidirectional two-sample MR approach. The data included immune cell data from Orrù et al.

Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis.

Objectives: Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS).

Method: Pooled data from Phase 2 (NCT01786668; 04/2013-03/2015)/Phase 3 (NCT03502616; 06/2018-08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts).

New onset heart failure in adolescents with inflammatory joint disease treated with TNF-α inhibitors: a case-based review.

The safety of tumor necrosis factor (TNF) inhibitors has been demonstrated for over two decades. However, their effects on cardiovascular function in patients with rheumatic diseases remain controversial, and conclusions are additionally hampered by the cardiovascular complications inherent in such diseases. We present two 15-year-old patients diagnosed with ankylosing spondylitis and juvenile idiopathic arthritis classified as polyarthritis with positive rheumatoid factor, respectively.

IDO1-mediated M2 macrophage polarization alleviates the progression of ankylosing spondylitis.

Indoleamine 2,3-dioxygenase 1 (IDO1) plays an anti-inflammatory role in autoimmune disease. However, its specific function in ankylosing spondylitis (AS) remain unclear. This study aimed to investigate the potential role of IDO1 in AS.

Inhibition of the Binding of Interleukin 17A with Interleukin 17A Receptor as a Treatment for Immune System and Inflammation Disorders, Cancer, and Neurodegenerative Diseases.

The invention in this patent application relates to -(2-amino-2-oxoethyl)heteroarylcarboxamide derivatives, represented herein generally by formula 1. These compounds are inhibitors of the binding of interleukin 17A (IL-17A) with its receptor IL-17RA and may potentially be used for the treatment of diseases or disorders associated with IL-17A activity, which include psoriasis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis, cancer, and neurodegenerative disorders.

Usenamine A: a potential therapeutic agent for rheumatoid arthritis and ankylosing spondylitis through its anti-inflammatory activity.

Background: Usenamine A (UA) is a natural compound isolated from the lichen , and its therapeutic effects on rheumatic diseases are not well understood. This study aimed to evaluate the potential anti-inflammatory effects of UA and its therapeutic effects on rheumatoid arthritis (RA) and ankylosing spondylitis (AS).

Materials And Methods: Molecular docking was performed between the 3D structure of UA and the TNF-TNFR2 complex.

[Assessment of residual symptoms in patients with axial spondyloarthritis with low disease activity and analysis of its related factors].

Objective: To comprehensively assess the occurrence of residual symptoms in patients with axial spondyloarthritis who have successfully attained the treatment goal of low disease activity, and to conduct a thorough analysis of the related factors.

Methods: An analysis was performed on axial spondyloarthritis patients who achieved low disease activity for the first time during their visits at the Rheumatology and Immunology Department of Peking University Third Hospital, spanning from May 1, 2021, to February 29, 2024. Based on the ankylosing spondylitis disease activity score-C-reactive protein (ASDAS-CRP), the patients who achieved low disease activity were divided into a non-remission low disease activity group and a remission group.

Literature review of the clinical features of sulfasalazine-induced drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).

Background: Sulfasalazine (SSZ) is commonly prescribed for the treatment of ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis. However, it can also trigger a severe drug reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Drug-Induced Hypersensitivity Syndrome (DIHS). This article aims to analyze the clinical characteristics of DRESS/DIHS induced by SSZ and provide evidence for clinical diagnosis, treatment, and prevention.

Ankylosing spondylitis and cardiovascular disease: A two-sample Mendelian randomization analysis.

Epidemiological research has demonstrated that people suffering from ankylosing spondylitis (AS) have a greater chance of developing cardiovascular disease (CVD), though the potential link between AS genetics and CVD risk is uncertain. This research examined the potential link between CVD outcomes and AS which is genetically determined. A two-sample Mendelian randomization analysis was conducted using data from European population genome-wide association study of AS and CVD.

The mediating role of the genetically predicted N6, N6, N6-trimethyllysine levels in the association between HLA DR on CD14- CD16+ monocytes and ankylosing spondylitis.

This study explores the hidden connection between HLA DR on CD14- CD16+ monocytes and ankylosing spondylitis (AS), with a particular emphasis on investigating and measuring the impact of 1091 blood metabolites as potential mediators. We harnessed the power of summary-level data extracted from a comprehensive genome-wide association study to delve into the intricate relationship between genetically predicted HLA DR on CD14- CD16+ monocytes (3621 cases) and AS (1193 cases and 374,621 controls). Furthermore, we employed a two-step Mendelian randomization (MR) methodology to elucidate the extent to which blood metabolites contribute to the effects observed in CD14- CD16+ monocytes, ultimately influencing the development of AS.

Efficacy and Safety of CT-P13 as First- and Second-Line Treatment in Patients with Ankylosing Spondylitis.

CT-P13 is a biosimilar version of infliximab, a monoclonal antibody. In individuals with ankylosing spondylitis (AS), CT-P13 has been shown to be effective and to have a well-tolerated safety profile. The aim of this study was to evaluate the long-term drug persistence, safety, and efficacy of infliximab biosimilar CT-P13 in patients with AS undergoing first-line (1st-line) and later (≥2nd-line) treatment in clinical practice.

Wnt5a exacerbates pathological bone features and trabecular bone loss in curdlan-injected SKG mice via osteoclast activation.

Many studies on osteoblasts have suggested that Wnt5a plays a crucial role in excessive osteoblast activity, which is responsible for ectopic new bone formation, but research on osteoclasts in ankylosing spondylitis (AS) remains relatively limited. This study aimed to explore whether Wnt5a influences osteoclast-mediated bone resorption in curdlan-injected SKG mice, a model that mimics AS. Compared to the Vehicle group, the Wnt5a treatment group exhibited statistically higher clinical arthritis scores and increased hindpaw thickness values.

Exploring T Cell and NK Cell Involvement in Ankylosing Spondylitis Through Single-Cell Sequencing.

To uncover the complex immune mechanisms driving inflammation in ankylosing spondylitis and lay the groundwork for identifying new therapeutic targets and innovative approaches, we conducted 10× single-cell sequencing on bone marrow cell samples collected from the vertebrae of three AS patients and three non-AS patients. Using single-cell sequencing data, we analysed the expression of differentially expressed genes (DEGs) by comparing AS patients with non-AS patients. Key genes among the related DEGs were identified through protein-protein interaction networks and hub gene screening and further validated using immunohistochemistry.

Updating the 2019 ACR/SAA/SPARTAN Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis (SPARTAN 2024 Annual Meeting Proceedings).

Purpose Of Review: Since the publication of the 2019 American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (ACR/SAA/SPARTAN) treatment recommendations for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (axSpA), new evidence has emerged that necessitates a revision of the ACR/SAA/SPARTAN clinical practice guideline (CPG).

Recent Findings: An online survey was conducted among SPARTAN members prior to the 2024 Annual Meeting, with 81 members participating. A majority (62%) expressed a preference for treating axSpA as a single entity in the updated CPG, eliminating the distinction between AS and nonradiographic axSpA.

What Could Lead to the Production of Anti-Rheumatoid Antibodies in Patients with Brucellosis Spondylodiscitis: Possible Causes.

Background: High titers of specific antibodies to cyclic citrulline peptide (ACCP) are often present in the serum of patients with rheumatoid arthritis (RA) and, together with rheumatoid factor (RF), are a diagnostic marker of RA. Brucellosis is a zoonotic infection in which osteoarticular involvement occurs in 10-85% of patients. RF in brucellosis patients is significantly higher than in healthy people.

Osteomalacia: A Challenging Diagnosis Adverse Event Associated with Intravenous Ferric Carboxymaltose-A Case Report.

Hypophosphatemia resulting from intravenous iron treatment has become an increasingly concerning syndrome in recent years. We report the case of a 66-year-old male patient with a medical history of ankylosing spondylitis (AS), Crohn's disease, and chronic iron deficiency. Following intravenous iron infusions of ferric carboxymaltose, the patient developed diffuse bone pain and multiple bone fractures.

Colon mucosal proteomics of ankylosing spondylitis versus gut inflammation.

Objective: Ankylosing spondylitis (AS) patients often present with microscopic signs of gut inflammation. We used proteomic techniques to identify the differentially expressed proteins (DEPs) in the colon tissues of patients with AS and patients with gut inflammation, and then used investigated the influence of NMRAL1 protein on inflammatory cytokines to explore its potential role in the pathogenesis of AS and gut inflammation.

Methods: Colonic mucosal tissues were collected from four different groups: healthy individuals (group A), patients with gut inflammation only (group B), patients with AS only (group C), and patients with AS combined with gut inflammation (group D).

Improvement of Fatigue in Patients with Ankylosing Spondylitis Receiving Tofacitinib: Analyses of a Phase 3 Randomized Controlled Trial.

Introduction: Fatigue is a key symptom in patients with ankylosing spondylitis (AS). The objective of this analysis was to estimate the median time to initial and stable improvement events in fatigue in patients with AS receiving tofacitinib.

Methods: This post hoc analysis used data from a phase 3 trial (NCT03502616) in patients with active AS receiving tofacitinib 5 mg twice daily or placebo.

Case Report: A Young Woman Diagnosed With Overlap Syndrome of Systemic Sclerosis and Ankylosing Spondylitis.

This case report describes a rare occurrence of a 25-year-old female diagnosed with both systemic sclerosis (SSc) and ankylosing spondylitis (AS), two distinct autoimmune diseases. The patient presented with a combination of symptoms, including progressive skin tightening, lumbosacral pain, and Raynaud's phenomenon, which complicated the diagnosis. Despite the challenges posed by the coexistence of SSc and AS, a multidisciplinary treatment approach involving corticosteroids, immunosuppressants, and supportive therapies led to significant clinical improvement.

Strategizing Simultaneous Spinal Osteotomy and Total Hip Replacement in Ankylosing Spondylitis.

Objective: Ankylosing spondylitis (AS) is a debilitating rheumatic condition that significantly impairs mobility and quality of life through chronic inflammation and spinal fusion. The aim of this study is to investigate the optimal sequencing of spinal osteotomy and total hip replacement (THR) as treatment options, a topic that remains a subject of debate among medical professionals.

Methods: In a retrospective cohort study spanning from 2017 to 2021, we assessed adult patients with AS who underwent both spinal osteotomy and THR, outcome measures involved radiographic assessments like Global Cobb angle, thoracolumbar kyphosis (TLK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS), as well as clinical metrics such as the Harris hip score.

Advancements in Imaging Techniques for Early Diagnosis and Management of Axial Spondyloarthritis.

Purpose Of Review: We aimed to introduce recent finding of imaging studies used in axial spondyloarthritis (axSpA).

Recent Findings: Using low-dose whole spine CT (CT syndesmophyte score [CTSS]) improved diagnostic accuracy for evaluating spinal structural progression than previous method (modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) in axSpA. The novel definition of positive finding of sacroiliac joint (SIJ) and spine magnetic resonance imaging (MRI) enabled to diagnose axSpA earlier than plain radiography.