OBJECTIVE:To evaluate the relationship between biological ages and the prevalence and incidence of osteoarthritis (OA). METHODS:332 261 participants from UK Biobank were analyzed. Biological aging was measured using phenotypic age (PhenoAge) and Klemera-Doubal (KDMAge). KDMAge was derived from nine clinical biomarkers to gauge system integrity decline, while PhenoAge was computed from chronological age and nine clinical biomarkers to gauge mortality risk. Biological aging accelerations were computed as residuals from regressing KDMAge and PhenoAge against chronological age. The associations between biological aging and prevalence and incidence of OA were analyzed using logistic and Cox regression models. RESULTS:At baseline, 55.4% of included individuals had younger PhenoAge aging acceleration. In cross-sectional analyses, individuals with accelerated aging had higher odds of OA compared to those with non-accelerated aging (odds ratios [OR]: 1.12 [95% CI: 1.09-1.14] for PhenoAge acceleration and 1.05 [1.03-1.08] for KDMAge acceleration). In the longitudinal analyses, increased PhenoAge acceleration was associated with a higher risk of incident OA (hazard ratios [HR]: 1.12 [1.10-1.15]). However, the association between KDMAge acceleration and the incidence of OA was not statistically significant (HR: 0.99 [0.97-1.01]). Accelerated biological aging showed a more pronounced association with OA among individuals > 60 years. No additive or multiplicative interactions were found between OA polygenic risk score (PRS) and biological aging. CONCLUSION:Advanced biological aging may increase the risk of OA, independent of OA genetic risk, particularly in individuals aged over 60 years. The two biological aging indicators hold potential as novel composite clinical biomarkers, directing prevention and intervention strategies for high-risk populations for OA.
BACKGROUND:Rheumatoid Arthritis (RA) is a Prevalent Autoimmune Disorder Affecting Millions of People Worldwide. A Thorough Understanding of Its Clinical and Pathological Features Is Essential to Improve Patient Outcomes. METHODS:This Study Combined Data-Independent Acquisition Proteomics and Enzyme-Linked Immunosorbent Assay (ELISA) to Identify and Validate Potential Plasma Protein Biomarkers for the Early Diagnosis of RA. RESULTS:Differential Proteomic Analysis Identified Differentially Expressed Proteins Between Patients With RA and Healthy Controls and Characterized Their Functions. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Enrichment Analyses Were Performed to Explore Protein Functions and Associated Biological Pathways. The STRING Database and the Metascape Platform Were Used to Conduct an in-Depth Analysis of the Protein-Protein Interaction Network, Highlighting the Functional Attributes and Interconnections of Upregulated Proteins and Identifying Key Protein Complexes Involved in RA. ELISA Analysis of Plasma Samples Revealed Significantly Elevated SERPINA3 Levels in Patients With RA, Which Were Positively Correlated With Disease Activity Indicators-Including Erythrocyte Sedimentation Rate, C-Reactive Protein, and Disease Activity Score 28-But Were Not Correlated With Rheumatoid Factor or Its Subtypes. CONCLUSIONS:This Study Provides New Insights and Identifies Potential Biomarkers for the Early Diagnosis of RA.
OBJECTIVES:Behçet's disease (BD) is a chronic, multisystem immune-mediated vasculitis. A significant number of patients with BD have inflammatory comorbid (IC) disease that can affect the clinical course of the disease. In the current literature, there is no study which investigated IC disease in BD. It was aimed to show the prevalence and clinical spectrum of IC disease in patients with BD. METHODS:A total of 1591 patients diagnosed with BD and followed at five tertiary healthcare facilities were enrolled in the study. Patients were divided according to the presence of IC disease. Demographic characteristics, clinical manifestations, and laboratory parameters were systematically noted from medical records. The activity of the disease was evaluated by Behçet's Disease Current Activity Form (BDCAF). RESULTS:Inflammatory comorbid diseases were identified in 246 (15.3%) patients. The most common comorbidities were axial spondyloarthritis (n = 115, 7.2%), familial Mediterranean fever (FMF) (n = 38, 2.4%), and hidradenitis suppurativa (n = 37, 2.3%). Patients with IC disease had a greater use of anti-TNF treatment (p = 0.03). In the multivariate analysis, older age, and longer disease duration were found to be significantly associated with IC disease in BD (p < 0.05). CONCLUSION:BD can be associated with other inflammatory conditions. Furthermore, patients with inflammatory comorbidities were more likely to receive anti-TNF therapy, although this may partly reflect treatment indications for the comorbid conditions themselves. Therefore, clinicians should remain vigilant for inflammatory comorbidities, as their recognition may have implications for therapeutic decision-making.
INTRODUCTION:Knee osteoarthritis (OA) causes chronic pain and disability, with limited benefit from conventional treatments. Platelet-rich plasma (PRP) has been proposed as a biologic therapy with potential tissue-repair properties; however, its clinical efficacy remains uncertain. OBJECTIVE:To assess the effectiveness of intra-articular PRP injections in reducing pain and improving function in patients with knee OA. METHODOLOGY:This systematic review and meta-analysis included randomized controlled trials comparing intra-articular PRP with placebo or no treatment. Pain outcomes were measured using the Visual Analog Scale (VAS), while functional outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) or Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS:PRP significantly reduced pain and improved function compared with placebo across short-, mid-, and long-term follow-up. The magnitude of benefit varied but remained clinically relevant. CONCLUSION:PRP provides significant improvements in pain relief and functional outcomes compared with placebo or no treatment in patients with knee OA, supporting its potential as a therapeutic option. Standardized protocols and larger RCTs are warranted to further confirm its clinical effectiveness.
OBJECTIVES:To investigate whether immunosuppressant (IS) use contributes to the inverse association between rheumatoid arthritis (RA) and Alzheimer's disease (AD). METHODS:We analyzed NHANES 2011-2014 data, including 217 RA patients aged ≥ 60 years on prescription medications. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST), CERAD, Animal Fluency Test (AFT), and a global cognition z-score (Z-score). Associations between IS use and cognition were evaluated using multivariable linear regression. Additionally, two-sample Mendelian randomization (TSMR) and multivariable MR (MVMR) analyses were performed with GWAS datasets for RA, AD, and IS to examine potential causal effects. RESULTS:We observed that patients with RA using IS performed better in z.DDST (β: 0.335, p = 0.036) and Z-score (β: 0.214, p = 0.032) after adjusting for covariates, with sex-specific differences in cognitive domains. TSMR indicated that genetically predicted RA was associated with lower AD risk (OR: 0.936, p = 4.531E-04), and this effect was largely mediated by IS use. MVMR further validated the independent neuroprotective effect of IS on AD (OR = 0.884, p = 0.003) after adjusting for glucocorticoid and NSAID use, while these other medications showed no significant association with AD risk. CONCLUSIONS:These results suggest that the reduced risk of AD observed in RA patients may be partly related to IS use, highlighting a potential role of IS in improving cognitive function and modulating AD risk.
BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and joint damage. Toll-like receptor 7 (TLR7), one of the innate immunity receptors, plays a role in releasing inflammatory mediators like cytokines and histamine. These mediators are crucial in inducing and maintaining chronic inflammation in the joints. This study examines the relationship between histamine receptor 2 (H2R) and TLR7 expression in peripheral blood mononuclear cells (PBMCs) and evaluates plasma levels of histamine, IL-10, and TNF-α in RA patients. METHODS:The study included 60 RA patients (22 newly diagnosed and 38 undergoing treatment) and 30 healthy controls. H2R and TLR7 gene expression in PBMCs was measured using Real-time PCR (RT-PCR), while plasma levels of histamine, TNF-α, and IL-10 were assessed using ELISA. RESULTS:H2R and TLR7 gene expression in PBMCs was significantly higher in RA patients than in controls (p = 0.0013, p = 0.0057), with newly diagnosed patients showing increased H2R expression compared to treated individuals (p = 0.0004). Plasma levels of histamine, TNF-α, and IL-10 were elevated in RA patients, with higher histamine and TNF-α levels in newly diagnosed cases and increased IL-10 in treated patients (p = 0.0253). Significant correlations were observed between H2R and TLR7 expression (R = 0.68, p < 0.0001) and between H2R expression and histamine levels (R = 0.34, p = 0.01). CONCLUSIONS:Our study suggests a potential link between H2R signaling and TLR7 activation in RA. The therapeutic potential of H2R inhibitors and TLR7 antagonists in mitigating RA progression warrants further investigation.
BACKGROUND:The unique characteristics of the Asia Pacific called for the development of pragmatic and viable guidelines for the management of juvenile idiopathic arthritis (JIA). These consensus recommendations represent the second part of the guideline intending to offer an updated and regionally relevant framework for the management of systemic JIA (sJIA)/juvenile Still's disease. METHODS:A multidisciplinary task force of 35 members from 14 countries, including pediatric and adult rheumatologists as well as patient representatives, was convened. The guideline development followed the GRADE, ADAPTE, and AGREE II frameworks. Relevant international guidelines were critically appraised, and a systematic literature review was performed to address 10 PICO questions. Draft statements were discussed and voted upon using a modified Delphi process, with consensus defined as ≥ 80% agreement. RESULTS:Four overarching principles and eighteen statements, including five statements addressing macrophage activation syndrome (MAS) were formulated. The recommendations align with international guidelines, advocating early use of IL-1/IL-6 inhibitors, avoidance of glucocorticoid monotherapy in sJIA without MAS, promoting tapering of glucocorticoids once inactive disease is achieved, alongside class switching for biologic refractory cases and a treat-to-target approach akin to EULAR/PReS guideline. Additional features include recommending conventional synthetic DMARD when biologics are unavailable and listing the options, acknowledging regional health system heterogeneity in the Asia Pacific, mentioning tapering strategy, discouraging NSAIDs as initial monotherapy, highlighting non-biologic salvage options, and placing less emphasis on sJIA-associated lung diseases. CONCLUSION:These recommendations provide direction for practitioners caring for sJIA patients in limited resource areas to avoid treatment delay, hence improve overall outcomes. A shared decision approach and treat-to-targets are emphasized.
OBJECTIVE:Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major extra-articular complication contributing to increased morbidity and mortality. Circulating microRNAs (miRNAs) have emerged as potential non-invasive biomarkers in autoimmune diseases. This study aimed to evaluate whether plasma miRNA-7-5p and miRNA-214-5p are associated with the presence of RA-ILD and with radiological and functional indicators of pulmonary involvement. METHODS:In this cross-sectional study, 58 RA patients (29 RA-ILD, 29 without ILD) and 30 matched healthy controls were included. RA-ILD was diagnosed by multidisciplinary assessment (HRCT and pulmonary function tests). Plasma miRNA levels were measured by qRT-PCR and analyzed using the 2^-ΔΔCT method. Diagnostic performance was evaluated by ROC analysis. RESULTS:Plasma miRNA-7-5p and miRNA-214-5p levels were significantly higher in RA patients compared with healthy controls (p < 0.05 for both). Among RA patients, both miRNAs were significantly lower in those with ILD (p < 0.05). miRNA-7-5p demonstrated promising discriminatory performance for identifying RA-ILD (AUC = 0.87, 95% CI: 0.760-0.947; p < 0.001), whereas miRNA-214-5p showed modest accuracy (AUC = 0.676, 95% CI: 0.539-0.794; p = 0.01). In multivariable analysis, ILD presence was independently associated with decreased levels of both miRNAs. Neither miRNA correlated significantly with DAS28-CRP, disease duration, nor with radiological or functional severity parameters. CONCLUSION:Circulating miRNA-7-5p and miRNA-214-5p are associated with the presence of RA-ILD but do not reflect disease severity in this cohort. Larger prospective studies are required to validate their potential role as adjunctive biomarkers for RA-ILD detection and risk stratification.
