Search Results (509)

Background: Arthropathies are a substantial source of global morbidity and healthcare costs, and there is a clinical need for accessible tools capable of detecting inflammatory and metabolic changes beyond conventional structural imaging. This review consolidates the recent evidence on infrared thermography (IRT) as a diagnostic and monitoring adjunct in the major arthropathies. Methods: A structured narrative review was conducted. A literature search of PubMed, Web of Science Core Collection, and Scopus was performed to identify relevant studies published between January 2016 and December 2025 using thermography- and arthropathy-related keywords and controlled-vocabulary terms combined with Boolean operators; only original full-text studies in English published within the previous decade were eligible. The structured search yielded 53 primary studies. Additional sources, including narrative and systematic reviews, methodological references, and book chapters, were drawn upon to inform the Introduction, Discussion, and interpretation but were not included in the primary evidence synthesis. Results: Across the included studies, IRT detected clinically meaningful thermal changes in most cases of osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, Charcot neuroarthropathy, and post-arthroplasty states, with thermal signals correlating moderately with ultrasound-detected synovitis, inflammatory biomarkers, and symptom distribution. Discussion: The evidence base is heterogeneous, however: temperature distributions overlap substantially between patients and controls, well-conducted negative results exist for hand thermography in low-activity rheumatoid arthritis, and reported effect sizes vary widely across devices and protocols. Quantitative thermographic metrics and machine-learning approaches may further refine diagnostic performance and enable remote monitoring. Conclusions: IRT is a promising rapid, non-invasive, radiation-free adjunctive imaging modality, but its clinical adoption is constrained by methodological variability, environmental and vascular confounders, and the absence of prospective validation. Standardised acquisition protocols and prospective multi-site validation are required before routine clinical use. Full article

Systemic inflammation plays a pivotal role in the progression of rheumatoid arthritis (RA) and its associated comorbidities, ranging from cardiovascular (CV) disease to neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review examines the molecular cross-talk linking these pathologies, with a specific focus on the distinction between pentameric C-reactive protein (pCRP) and its proinflammatory monomeric form (mCRP). We discuss evidence suggesting that mCRP is not merely a passive marker but also an active driver of endothelial dysfunction, atherosclerosis, and synovial inflammation. This review further explores the connections among inflammatory biomarkers, blood vessel integrity, and neurodegeneration, detailing how persistent cytokine elevation (IL-6, TNF-α) and vascular injury contribute to cerebral small vessel disease (cSVD) and cognitive decline, with neurofilament light chain (NfL) serving as a key biomarker of neuroaxonal injury. Additionally, we address the neurobiology of pain in RA, highlighting the mechanisms of central sensitization (CS) and neuroimmune signalling that sustain pain-independent joint swelling. This evidence indicates that understanding the dynamic connection between CRP isoforms and neuronal markers should offer new insights for risk stratification and suggests that targeting mCRP may provide a novel therapeutic avenue to mitigate both articular and extra-articular manifestations of RA. Full article

Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by chronic synovial inflammation and progressive joint destruction. However, the molecular mechanisms and diagnostic biomarkers underlying RA remain unclear. In this study, we aimed to identify potential biomarkers for clinical diagnosis of RA and to investigate their association with immune infiltration. By integrating differentially expressed genes analysis (DEGs) and weighted gene co-expression network analysis (WGCNA), we identified PSMB9 as a hub gene associated with RA. Gene set enrichment analysis (GSEA) and immune infiltration analysis revealed a strong association between RA and macrophage infiltration. Single-cell RNA sequencing datasets also suggest that PSMB9 is not only highly expressed in macrophage but is also present in synovial cells. We employed cellular thermal shift assay (CETSA) combined with Western blot to validate the interaction between sinomenine (SIN) and the target protein. CETSA results demonstrated that, compared with the control group, SIN increased the thermal stability of PSMB9, suggesting direct binding between the two. Western blot experiments further confirmed that PSMB9 protein expression was significantly downregulated following SIN treatment. PSMB9 may serve as potential diagnostic biomarker and therapeutic targets for RA. Moreover, our data suggest SIN may exert anti-inflammatory effects through regulation of PSMB9. This study also provides an additional insight into the underlying mechanisms involved in the progression of RA and discover a new molecular target for SIN. Full article

Background/Objectives: Response to TNF inhibitors in RA remains heterogeneous and reliable predictors of treatment response are still lacking. Biomarker-based stratification may improve therapeutic decision-making and aligns with the emerging paradigm of precision medicine. Methods: We conducted a prospective observational study including 64 biologic-naïve patients with active RA being inadequately controlled by csDMARDs. All patients initiated anti-TNF therapy and were followed for 12 months. Clinical response was assessed at 6 and 12 months using EULAR response criteria based on DAS28-CRP. Baseline serum levels of classical biomarkers (RF type IgM, RF type IgA, anti-CCP) and additional biomarkers (anti-MCV,14-3-3η protein, COMP) were evaluated. Logistic regression analyses were performed to identify predictors of treatment response. Results: At 6 months, 7 patients were classified as non-responders, 38 as moderate responders, and 19 as good responders Lower baseline levels of RF isotypes, anti-CCP antibodies, 14-3-3η protein, and COMP were associated with favorable clinical response at 6 months. Baseline anti-CCP and 14-3-3η protein levels emerged as significant predictors in univariate analysis. Multivariate logistic regression yielded a predictive model incorporating anti-CCP, 14-3-3η protein, and COMP, achieving an overall prediction accuracy of 89.1%. At 12 months, baseline RF isotypes remained associated with treatment response, whereas the predictive value of other biomarkers diminished. Longitudinal analysis demonstrated significant reductions mainly for classical autoantibody levels under anti-TNF α inhibitors. Conclusions: A combined serum biomarker panel may support early prediction of response to anti-TNF therapy in RA. These findings highlight the potential of integrated biomarker-based stratification to optimize therapeutic decisions and support the implementation of precision medicine approaches in RA. Full article

Arthritis (RA) is characterized by immune-mediated chronic inflammation and endothelial dysfunction, ultimately resulting in clinically overt cardiovascular complications. As a prototypical disease of microvascular dysfunction, RA represents an ideal model to study microvascular alterations. The dermal capillary network offers an easily accessible window to the peripheral microcirculation, whose function can be easily assessed using Nailfold videocapillaroscopy (NVC) or laser techniques. Whereas the clinical significance of structural alterations is not always clear, functional abnormalities may provide more direct insight into the dynamic status of the microvasculature and endothelial integrity. The present narrative review aims to provide an integrative overview of available studies evaluating functional abnormalities of the dermal microcirculation in RA, with particular emphasis on the emerging role of NVC as a dynamic vascular assessment tool. Several studies in RA have assessed the structure and morphology of the peripheral microvasculature using NVC, but far fewer data exist on functional alterations assessed with this method. The study of functional alterations of the dermal microvascular network in RA has largely been based on laser techniques, which consistently point towards altered microvascular reactivity. By contrast, functional NVC-related approaches remain limited, despite their potential ability to simultaneously assess structural and dynamic capillary abnormalities in vivo. Available evidence supports that NVC may be reframed as a promising functional vascular biomarker in RA. However, the available literature is characterized by small sample sizes, predominantly cross-sectional designs, and methodological heterogeneity, highlighting the need for standardized prospective studies. Full article

Periodontitis (PD) and rheumatoid arthritis (RA) are chronic inflammatory disorders that impose substantial individual and societal burdens worldwide. PD is characterized by progressive destruction of the periodontal ligament and alveolar bone, leading to tooth loss, impaired oral function, and sustained systemic inflammatory burden. RA, affecting approximately 0.5–1% of the population, is a chronic autoimmune disease marked by persistent synovial inflammation, progressive joint destruction, disability, and reduced quality of life. Increasing evidence indicates that these conditions are biologically and clinically interconnected. Both diseases share key pathogenic pathways, including microbial dysbiosis, immune dysregulation, chronic inflammation, genetic susceptibility, and aberrant autoantibody responses. Particular attention has focused on keystone periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which may promote protein citrullination and the formation of anti-citrullinated protein antibodies (ACPA), thereby providing a plausible mechanistic bridge between periodontal infection and systemic autoimmunity. Shared genetic risk factors, including HLA-DRB1 susceptibility alleles, further support a common host predisposition. Clinical, epidemiological, and translational studies increasingly support a bidirectional association. Individuals with PD appear to have a higher risk of RA development, whereas patients with RA demonstrate greater prevalence, severity, and progression of periodontal disease. Interventional studies suggest that nonsurgical periodontal therapy may reduce local periodontal inflammation, circulating inflammatory biomarkers, and RA disease activity indices, while effective pharmacological control of RA may also improve periodontal outcomes. This narrative review critically evaluates the PD–RA relationship across four interconnected domains: (i) epidemiological and clinical associations between PD and RA, (ii) key mechanisms underlying RA pathogenesis, (iii) shared biological pathways linking both diseases, and (iv) the extent to which treatment of one condition influences the other. Particular emphasis is placed on major sources of heterogeneity and confounding—including smoking, metabolic comorbidities, disease stage, therapeutic exposure, and variable diagnostic definitions—that may explain inconsistencies across the literature. By integrating current mechanistic and clinical evidence, this review provides a structured synthesis that extends beyond a descriptive overview of association studies. A clearer understanding of the periodontal–rheumatologic axis may facilitate risk stratification, identify novel therapeutic targets, and support integrated multidisciplinary care. Targeting both oral and systemic inflammation may improve outcomes in patients with coexisting PD and RA and may potentially reduce the risk or severity of one condition in individuals already affected by the other. Full article

The autoantibody reactome refers to the multidimensional repertoire of antibody reactivities against self-antigens across the human proteome or selected antigenic compartments. This offers a scalable systemic layer for precision immunology across spontaneous autoimmunity and treatment-induced immune toxicity. Autoimmune diseases and immune-related adverse events (irAEs) share major features of dysregulated immunity, yet clinically useful tools for risk stratification, early detection, endotyping, and treatment guidance remain limited and slow. A central challenge is that tissue pathology is highly informative but not uniformly accessible across diseases and organ systems, whereas routine serology captures only a narrow fraction of immune heterogeneity. In this perspective, I argue that a global autoantibody reactome can serve as a central unifying framework linking systemic immune history, tissue pathology, and clinical trajectories across autoimmune disorders and irAEs. Rheumatoid arthritis (RA) provides a strong prototype because its serological diversity, major role of post-translationally modified autoantigens, and marked synovial heterogeneity allow reactome features to be interpreted against tissue biology. Immune checkpoint inhibitor-associated inflammatory arthritis serves as an illustrative rheumatic irAE and a model of treatment-induced immune dysregulation with clear opportunities for longitudinal blood-based profiling. Spatial transcriptomics and proteomics are therefore positioned not as stand-alone solutions, but as mechanistic tools that can decode reactome-defined immune states within tissue microenvironments where tissue is accessible. Clinical translation will require integration of autoantibody reactomes with tissue, circulating proteomic, imaging, genetic, and clinical data through transparent multimodal models, as well as a shift from exploratory resources such as AAgAtlas toward analytically validated and clinically interpretable biomarker panels for risk prediction, endotyping, monitoring, and biomarker-guided intervention. This perspective outlines technical and strategic steps toward clinically actionable decision support, including risk stratification before ICI initiation and treatment guidance for patients who develop ICI-induced inflammatory arthritis, through integration of autoantibody reactome profiling, spatial omics and transparent multimodal AI. Full article

Methotrexate (MTX) remains the first-choice treatment for rheumatoid arthritis (RA), but individual variability in response and adherence underscores the need for reliable biomarkers of long-term drug exposure. Intracellular methotrexate polyglutamates (MTXPGs), typically measured in red blood cells (RBCs), fulfill this role but require invasive venous sampling. This study aimed to develop and validate a multi-matrix LC–MS/MS method for measuring MTXPGs in capillary blood samples obtained via volumetric absorptive microsampling (VAMS) and dried blood spots (DBS), and to compare these methods with traditional matrices. The method was validated in accordance with ICH M10 guidelines across RBC, whole blood (WB), VAMS, and DBS samples. MTX and MTXPG_2–5 and total MTXPG were measured in 40 matched clinical samples. MTXPG_6–7 were not detected across the tested clinical samples. Validation using Passing–Bablok regression, Bland–Altman analysis, and Spearman correlation showed strong agreement between VAMS and DBS (slopes 0.95–1.07; bias −4.21% to 0.36%; SRCC ≥ 0.969), with up to 100% of samples within ±20% of the agreement limits for total MTXPG. Significant differences were observed between capillary matrices and RBCs, with higher MTXPG levels in erythrocytes (bias up to −28%). Whole blood showed closer agreement with microsampling methods. ISR pass rates ranged from 84% to 95%, and stability tests indicated matrix- and chain length-dependent degradation, particularly for long-chain MTXPGs. These findings show that VAMS and DBS yield comparable results and can be considered interchangeable within a capillary-sampling framework. However, interpretation must account for matrix-specific differences when relating measurements to RBC-based reference values. This validated method could support the analytical feasibility of decentralized MTXPG monitoring in RA. However, prospective studies linking matrix-specific thresholds with disease activity, adherence, and toxicity are required before implementation for therapeutic decision-making. Full article

Background: In psoriatic arthritis (PsA), clinical tenderness and ultrasound (US) capture distinct yet related aspects of entheseal disease activity. However, their longitudinal relationship after initiation of biologic disease-modifying antirheumatic drugs (bDMARDs), and the clinical significance of early discordance during follow-up remain unclear. Methods: In this retrospective observational cohort study based on routinely collected medical records, patients with CASPAR-defined PsA and clinically and ultrasonographically active enthesitis at baseline (Clin+/US+) who initiated bDMARD therapy underwent paired, same-day, blinded clinical and US assessments at approximately 6 and 12 months. Agreement between clinical and US findings was quantified using Cohen’s kappa. Discordant states (Clin−/US+ and Clin+/US−) were prespecified, and predictors of Clin−/US+ status at 6 months were analyzed using models that accounted for within-patient clustering. Results: Thirty-nine patients contributed 82 entheses and were treated with either tumour necrosis factor inhibitors (53.8%) or interleukin-17 inhibitors (46.2%). At 6 months, agreement between clinical and US assessments was fair (κ = 0.286; 95% confidence interval [CI], 0.080 to 0.492), with 23.2% of entheses classified as Clin−/US+ and 52.4% as concordantly inactive. At 12 months, agreement improved to substantial-to-almost-perfect levels (κ = 0.779; 95% CI, 0.595 to 0.963), with only 1.2% of entheses remaining Clin−/US+ and 80.5% achieving concordant remission. NSAID exposure was the only significant predictor of Clin−/US+ status at 6 months in univariable analysis (odds ratio [OR], 3.82; 95% CI, 1.27 to 11.47; p = 0.017) and remained associated after multivariable adjustment (OR, 6.16; 95% CI, 1.14 to 33.2; p = 0.03). Conclusions: In PsA patients starting bDMARD therapy, clinical and US assessments of enthesitis showed partial discordance at 6 months, followed by greater convergence at 12 months. These findings suggest that clinical and imaging abnormalities may resolve asynchronously during follow-up and should therefore be interpreted in an integrated, time-aware manner. Residual US abnormalities in the setting of clinical improvement should be interpreted cautiously and within the broader clinical context. Full article

Crohn’s disease (CD) in children with juvenile idiopathic arthritis (JIA) is frequently diagnosed late due to overlapping symptoms and non-specific biomarkers. We hypothesized that longitudinal cytokine profiling could identify a pre-symptomatic signature predictive of CD conversion in pediatric JIA patients. Ninety pediatric participants (JIA, CD, psoriatic arthritis, healthy controls) underwent serum cytokine profiling (IL-1α, IL-1β, IL-36α, IL-37, IL-6, IL-18, IL-27, IL-31) at baseline and 12 months. Statistical analysis used Mann–Whitney U tests for two-group comparisons, the Kruskal–Wallis test with Dunn’s post hoc for multi-group comparisons, Fisher’s Exact Test for categorical outcomes, and exploratory principal component analysis (PCA). Baseline screening identified a subgroup of JIA patients (N = 4) with significantly elevated IL-1α, IL-1β, and IL-36α. At 12 months, all four patients in this subgroup received a secondary CD diagnosis (4/4 converters vs. 0/21 non-converters; Fisher’s Exact Test: p < 0.0001). The longitudinal analysis at conversion revealed a broader pro-inflammatory shift, with marked increases in IL-18 and IL-31, alongside elevated IL-37, suggesting a compensatory regulatory response. PCA confirmed that converters clustered distinctly from both stable JIA and established CD. A baseline IL-1 family signature may represent a preliminary predictive signature for CD onset in pediatric JIA. Although constrained by the small converter subgroup (N = 4), these data support cytokine profiling for earlier diagnosis in high-risk populations. Full article

Background: Musculoskeletal pain remains a major cause of disability worldwide, encompassing disorders such as rheumatoid arthritis (RA), osteoarthritis (OA) and chronic back pain. Acupuncture and dry needling are increasingly used for symptom management, yet their effects on inflammatory modulation remain unclear. This systematic review and meta-analysis evaluated the influence of acupuncture on inflammatory biomarker regulation in musculoskeletal pain. Methods: Following PRISMA and Cochrane methodological guidelines, comprehensive searches were conducted across MEDLINE (via PubMed), Web of Science, Cochrane Library, Scopus, Google Scholar, and OpenEvidence from inception to August 2025. Eligible studies were randomized controlled trials (RCTs) involving acupuncture or dry needling interventions with inflammatory biomarker outcomes. Screening, data extraction, and risk of bias assessment using ROB2 were performed by two reviewers independently. The certainty of evidence was appraised using GRADE criteria. The protocol was registered on PROSPERO (CRD420251011831). Results: Nineteen RCTs and one randomized cross-over study (n = 1492) met inclusion criteria. Some studies demonstrated reductions in CRP, ESR, IL-1β, IL-6 and TNF-α following acupuncture. Random-effects meta-analysis indicated that modified acupuncture (electroacupuncture or needle-knife therapy) significantly reduced TNF-α in knee OA compared with traditional acupuncture (SMD = −1.63, 95% CI −2.47 to −0.80, p < 0.01) but not IL-1β. However, no significant effects were observed from acupuncture versus sham acupuncture for CRP or ESR in patients with arthritis. However, the findings are limited by high heterogeneity and the small number of studies included in each meta-analysis. Conclusions: A moderate level of GRADE evidence suggests that modified acupuncture may be more effective than standard acupuncture in reducing TNF-α levels in patients with OA. Further high-quality biomarker-based RCTs are warranted to confirm these findings. This study received no external funding. Full article

Rheumatoid arthritis (RA) is a chronic disease that primarily manifests as symmetrical joint inflammation. Although Coix Seed Oil (CSO) has demonstrated anti-inflammatory effects in RA rat models, its systemic metabolic regulatory mechanisms remain unclear. Therefore, we aimed to investigate whether CSO ameliorates RA by modulating inflammation-associated metabolic pathways. Ultra-High-Performance Liquid Chromatography (UHPLC)-Q Exactive HF-X-MS-based metabolomics was used to profile metabolites in the synovial tissue and serum of complete Freund’s adjuvant (CFA)-induced RA rats. Systematically altered metabolites and their associated pathways were identified using multivariate analysis and pattern recognition. CSO treatment modulated 16 RA-related biomarkers in rat synovial tissues and 12 in the serum, which mainly affected amino acids, arachidonic acids, lipids, sphingolipids, and carnitines. These metabolites were associated with eight perturbed metabolic pathways that were predominantly involved in inflammatory responses. This study demonstrated that CSO has significant anti-RA effects on pharmacodynamic activity and metabolic network regulation. Additionally, inflammation-associated metabolic pathways are closely linked to the therapeutic efficacy of CSO in RA treatment. Full article

Intra-articular soft connective tissues such as synovium and adipose tissue play a crucial role in governing joint homeostasis and disease progression in various forms of arthritis. In the knee, like many synovial joints, adipose tissue forms an integrated anatomic and functional unit with the joint-lining synovium, and the most prominent adipose depot is the infrapatellar fat pad (IFP). With growing evidence that lipid profiles in the synovium–IFP unit shift during progression of joint diseases like osteoarthritis (OA), there is strong impetus for consistent tissue collection approaches and reproducible subsequent lipid characterization. Here, we present a standardized dissection and low-input untargeted lipidomics workflow optimized for mouse knee synovium and IFP, to enable comprehensive lipid profiling. Synovium/IFP from multiple joints are pooled to increase input mass and guarantee robust lipid yield, followed by lipid extraction and high-resolution liquid chromatography-mass spectrometry (LC–MS) acquisition for global, untargeted lipidomic profiling. The analysis workflow encompasses robust feature detection, accurate lipid annotation, data transformation and normalization. These steps enhance comparability across samples, particularly those with low input amounts, while minimizing technical variance and batch effects. Using this approach, we detect a broad spectrum of lipid species spanning the major lipid categories. As expected for untargeted discovery, a subset of non-lipid species is also observed. This protocol provides a practical framework for robust, reproducible lipidomics in murine intra-articular soft tissues to support future disease-specific biomarker and drug target discovery in OA and other joint diseases. Full article

Nigella sativa cold-pressed oil (NSO) is rich in nutrients and biologically active compounds. This study aimed to evaluate its effects on symptoms and serum levels of inflammatory and disease activity markers in rats with Freund’s adjuvant-induced arthritis (AIA). Animals were treated orally with NSO at doses of 1 and 3 mL/kg for two weeks before arthritis induction and throughout the experiment. Hind paw edema and nociceptive thresholds were measured by plethysmometer, Hargreaves apparatus, and Randall–Selitto test, respectively. At the end of the experiment, TNF-α, IL-1β, IL-10, brain-derived neurotrophic factor (BDNF), and neuropeptide Y (NPY) serum levels were measured. NSO preventive administration significantly reduced paw edema of the affected hind paw, along with an increase in the nociceptive threshold to both thermal and mechanical stimuli. Administration of NSO resulted in a significant reduction in serum levels of IL-1β and NPY (p < 0.01 and p < 0.05, respectively), while TNF-α and IL-10 levels remained comparable to those in the untreated AIA control group. These findings indicate that NSO exerts anti-inflammatory and analgesic effects and modulates circulating IL-1β and NPY (an independent marker associated with disease activity) in experimental arthritis. Full article

Oxidative stress is a key contributor to the pathogenesis of immune-mediated diseases through its effects on cellular metabolism, mitochondrial function, immune signaling pathways, and inflammatory tissue injury. Disruption of redox homeostasis promotes metabolic reprogramming and persistent activation of innate and adaptive immune responses, contributing to disease progression across multiple inflammatory and autoimmune disorders. Recent advances in high throughput molecular technologies have generated large scale multi-omics datasets that enable comprehensive investigation of redox-associated mechanisms at a systems level. Integration of these datasets with computational analytical approaches has facilitated the identification of multidimensional molecular signatures associated with disease development and progression. This systematic review evaluates studies applying computational frameworks to analyze redox-related molecular data in immune-mediated diseases including multiple sclerosis, systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, Sjögren’s syndrome, and inflammatory bowel disease. Across the reviewed studies, oxidative stress associated with molecular signatures were consistently linked to immune activation, mitochondrial metabolism, and inflammatory signaling pathways. Computational analyses also identified regulatory genes involved in antioxidant defense and metabolic regulation, as well as pathways associated with regulated cell death. These findings highlight the translational potential of computational redox analysis for biomarker discovery, disease stratification, and development of targeted therapeutic strategies aimed at restoring redox balance and improving clinical management of immune-mediated diseases. Full article