Osteoarthritis (OA) is a common joint disorder causing disability, marked by pain and stiffness, with current therapies only relieving symptoms. This highlights the need for early biomarkers. The urinary albumin-to-creatinine ratio (UACR) is an indicator of renal dysfunction and systemic inflammation, while OA is also closely associated with inflammatory processes. However, the direct relationship between UACR and OA risk remains unclear. We investigated the prospective association between UACR and incident OA. We analyzed data from 445,860 UK Biobank participants without OA, measuring UACR from urine samples and classifying it into normo- (< 30 mg/g), micro- (30 to 300 mg/g), and macroalbuminuria (> 300 mg/g). Incident OA was identified from medical records, and Cox models adjusted for various factors estimated hazard ratios and confidence intervals, with dose–response relationships assessed using cubic splines and further characterized by Kaplan–Meier curves and subgroup analyses. A median follow-up of nearly 18 years revealed a significant, dose-dependent link between UACR and OA, with HRs of 1.11 for microalbuminuria and 1.20 for macroalbuminuria compared to normo-albuminuria. A nonlinear, J-shaped relationship was observed, with OA risk increasing sharply after UACR exceeded approximately 25 mg/g—a threshold that aligns with the upper limit of mild microalbuminuria and may represent an early stage of subclinical vascular dysfunction. These findings were supported by Kaplan–Meier curves showing progressively higher OA incidence with rising UACR (log-rank P < 0.0001). This association was consistent across subgroups and highest in non-obese individuals (HR = 1.52 for UACR > 300 mg/g). Elevated UACR is linked to increased OA in a nonlinear manner, remaining significant after adjustments, suggests that UACR, as a marker of systemic microvascular and endothelial health, could help identify individuals at higher risk for OA, potentially enabling earlier and more targeted preventive interventions.
Isotretinoin is commonly used to treat severe acne vulgaris, and reports of inflammatory back pain (IBP) during therapy have grown over the past decade. Previous studies have reported improvement in musculoskeletal symptoms following isotretinoin discontinuation; however, persistent symptoms have also been described. This study aimed to describe the clinical and demographic characteristics of isotretinoin-associated IBP according to symptom persistence after isotretinoin discontinuation. This retrospective cohort study included 100 consecutive adults with new-onset IBP fulfilling ASAS criteria during isotretinoin therapy. Clinical, laboratory, and imaging data were collected. Patients were classified as persistent or non-persistent according to whether IBP continued beyond three months after isotretinoin discontinuation. The median age was 24 years, and 80
Interstitial lung disease (ILD) is a pulmonary manifestation of connective tissue diseases (CTDs). Limited data exist describing the epidemiology of CTD-ILD; therefore, this study aimed to estimate the incidence and prevalence of CTD-ILD in the US, overall and by CTD-ILD subtypes. Patients with CTD-ILD and rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), idiopathic inflammatory myopathy (IIM), mixed CTD (MCTD), and Sjögren’s disease (SjD) were identified from Optum® de-identified Electronic Health Record data set (Optum® EHR) and MarketScan® Commercial and Medicare US databases between 2019 and 2024. ILD was present in 4.3
Rheumatoid arthritis (RA) involves persistent immune dysregulation, but cell-specific genetically regulated pathways remain unclear. We integrated cell-specific genetic and multi-omics evidence to prioritize candidate regulatory pathways. cis-eQTLs from 17 immune-cell populations were integrated with RA GWAS data by two-sample Mendelian randomization. Transcriptomics, WGCNA, and machine-learning feature selection identified convergent candidates. Single-cell and virtual perturbation analyses assessed cellular localization and downstream changes. Molecular docking and dynamics computationally prioritized compounds, and knockdown/rescue experiments evaluated the PRKCB–CTSL relationship. Eleven candidates had convergent genetic and transcriptomic support. PRKCB was retained by LASSO, SVM, and random forest and preferentially expressed in monocytes. Virtual perturbation implicated CTSL and antigen-processing/presentation pathways. PRKCB knockdown reduced CTSL expression and NF-κB phosphorylation, whereas CTSL restoration partially rescued NF-κB phosphorylation. Separately, structure-based analyses computationally prioritized ursodiol for the most favorable predicted PRKCB interaction among evaluated compounds. Genetic, transcriptomic, single-cell, computational, and in vitro evidence supports monocyte-associated PRKCB–CTSL as a candidate regulatory pathway in RA. Further mechanistic and in vivo studies are required to establish its causal and pharmacological relevance.
Selective IgM deficiency (sIgMD) is an uncommon immunological phenotype characterized by persistently reduced serum IgM, but its characteristics within autoimmune rheumatic diseases (ARDs) remain poorly defined, particularly in Chinese populations. This study aimed to characterize a persistent isolated low IgM phenotype compatible with sIgMD from an ARD-centered perspective, focusing on its clinical features, and infection spectrum in a cohort of 257 patients. A retrospective study of adult inpatients diagnosed with both ARDs and persistent isolated low IgM was conducted. Data on demographics, ARD types, infections, treatments, and laboratory parameters were collected and analyzed. A total of 257 adult patients with ARDs and coexisting persistent isolated low IgM were included. The median age was 48 (35–60) years, with a female predominance (203/257, 79.0
