Arthritis Research & Therapy最新文献

Background: Psoriatic arthritis with inflammatory axial involvement (PsA-ax) and axial spondyloarthritis (axSpA) are distinct entities within the spectrum of spondyloarthritides. Despite overlapping clinical and imaging features, the extent and pattern of radiographic spinal progression in PsA-ax relative to axSpA remain insufficiently characterized.

Objective: To describe and analyse differences in radiographic spinal progression between axSpA and PsA-ax.

Methods: In this retrospective cohort study, 246 patients (axSpA: n=172; PsA-ax: n=74) with lateral radiographs of the cervical, thoracic, and/or lumbar spine were included. Radiographic progression was quantified using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). An adjusted linear mixed-effects model was used to analyse differences in the longitudinal association with mSASSS between axSpA and PsA-ax. The estimated β-coefficient along with the 95% confidence interval (CI) is reported.

Results: The mSASSS differed substantially at baseline, averaging 6 (SD 14) in axSpA and 0.96 (SD 2.12) in PsA-ax. The patient-level mean MSASSS change over 2 years was small overall, but higher in patients with axSpA than in those with PsA-ax, averaging 0.39 (SD 1.83) and 0.07 (SD 0.29), respectively. A total of 27% of axSpA and 5% of PsA-ax had a patient-level mean MSASSS change over 2 years >0 units. In the adjusted linear mixed-effects model, the estimated mean progression in mSASSS over two years was slightly lower in PsA-ax compared to axSpA (adjusted β = -0.088, 95% CI: -0.446 to 0.271).

Conclusion: Patients with PsA-ax were found to have slightly lower mean progression in mSASSS over two years than patients with axSpA. However, the wide CI crossing zero indicates large uncertainty and compatibility with no difference in mSASSS progression between PsA with axial involvement and axSpA, warranting further studies.

Background: Treatment of rheumatoid arthritis (RA) frequently requires Janus kinase inhibitors (JAKi) and biologic DMARDs (bDMARDs) with other mechanisms of action (OMA) after tumour necrosis factor inhibitors (TNFi) failure. Comparative safety data between JAKis and OMA in TNFi-inadequate responders (TNFi-IR) remain limited.

Objectives: To evaluate and compare safety profiles of JAKis versus OMA in TNFi-IR RA patients.

Methods: A retrospective cohort study followed 305 RA patients (163 JAKis; 142 OMA) previously treated with TNFi for up to 24 months. Incidence rates (IR) of adverse events (AEs) per 100 patient-years (PY) and incidence rate ratios (IRR) adjusted for disease activity and previous bDMARD exposure were calculated using Poisson regression.

Results: At baseline, OMA patients had higher disease activity (DAS28-CRP = 4.5 vs. 3.8), whereas comorbidities and other baseline characteristics were similar. Overall, AE incidence was higher with OMA (IR 111.6/100 PY) compared to JAKis (IR 65.3/100 PY; adjusted IRR 1.67, 95% CI 1.22-2.31). Serious AEs occurred more frequently with OMA (IR 11.7/100 PY) versus JAKis (IR 7.9/100 PY; adjusted IRR 0.41, 95% CI 0.18-0.95). Infection rates were comparable; herpes zoster occurred exclusively in the JAKi group during the initial year. Venous thromboembolism, cardiovascular events, and malignancies were rare and similar between groups.

Conclusion: In RA patients with inadequate response to TNFis, JAKis and OMA showed comparable safety profiles over 24 months. Serious AEs were numerically higher with OMA; herpes zoster was more frequent with JAKis. No new significant safety signals emerged.

Background: Arthritis imposes serious health consequences, including substantial disability and increased risk of all-cause mortality. Prior studies have reported that pain was associated with decreased health-related quality of life (HRQoL) among individuals with arthritis, yet the association between joint pain severity and HRQoL remains unclear.

Methods: This study analyzed pooled data from 362,366 U.S. adults with arthritis in the 2015-2019 Behavioral Risk Factor Surveillance Survey, categorizing joint pain severity as no/mild (0-3), moderate (4-6), or severe (7-10) via the Numerical Rating Scale. HRQoL was assessed using four domains: self-rated health, physical/mental unhealthy days, and activity limitation. Multivariable logistic regression examined the association between joint pain severity and loss of HRQoL in overall and across demographic subgroups.

Results: Compared to no/mild pain, moderate pain was associated with higher odds of poor self-rated health (OR = 2.18, 95%CI = 2.08-2.27), physical unhealthiness (2.46, 2.35-2.58), mental unhealthiness (2.05, 1.93-2.17), and activity limitation (2.33, 2.20-2.47). Severe pain showed stronger associations (e.g., poor self-rated health: OR = 4.61, 4.40-4.83; physical unhealthiness: 6.74, 6.41-7.09). Subgroup analyses revealed stronger associations in women, Non-Hispanic Whites, and adults aged 45-64 years. Joint pain severity was associated with worse HRQoL, with heterogeneous effects by demographic subgroups.

Conclusions: Moderate-to-severe joint pain is associated with poorer HRQoL across all domains, with severity-correlated HRQoL decline and subgroup variations. Targeted pain management strategies, particularly for severe pain and vulnerable populations, are critical to improving outcomes in arthritis.

Background: Bone marrow mesenchymal stem cell (BMSC) therapy can significantly improve the outcomes of rheumatoid arthritis (RA). This study explores the protective role of BMSC-derived exosomes (BMSCs-Exos) in RA through modulation of pyroptosis and mitochondrial integrity via the microRNA (miR)-515-5p/Toll-like receptor 4 (TLR4)/NOD-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD) pathway.

Methods: Exosomes were isolated from rat BMSCs, with or without miR-515-5p transfection. Exosomes were identified and analyzed through transmission electron microscopy, tunable resistive pulse sensing, and protein profiling via Western blot analysis. An in vitro RA model was established by stimulating RA fibroblast-like synoviocytes (RA-FLSs) with interleukin-1β (IL-1β). Co-culture of RA-FLSs with miR-515-5p-enriched BMSCs-Exos was used to evaluate inflammation, extracellular matrix (ECM) adhesion, migration, and invasion. Dual-luciferase reporter and RNA immunoprecipitation assays were performed to validate the targeting relationship between miR-515-5p and TLR4. Pyroptosis, reactive oxygen species (ROS) generation, and mitochondrial function were assessed. In vivo effects were confirmed using the collagen-induced arthritis (CIA) rat model.

Results: In RA-FLSs, BMSCs-Exos suppressed ECM adhesion, migration, and invasion, and attenuated IL-1β-induced inflammation through the TLR4/NLRP3/GSDMD pathway. BMSCs-Exos inhibited pyroptosis and improved mitochondrial function. Inhibition of miR-515-5p reduced cell viability, caused morphological changes, elevated cytosolic calcium (Ca²⁺), and increased mitochondrial ROS, activating caspase-dependent apoptosis and TLR4/NLRP3/GSDMD-mediated pyroptosis. In CIA rats, BMSCs-Exo treatment significantly alleviated joint damage, reduced pro-inflammatory cytokines, and protected against bone erosion.

Conclusion: BMSCs-Exos ameliorate RA progression by secreting miR-515-5p, which targets the TLR4/NLRP3/GSDMD pathway, thereby inhibiting pyroptosis and preserving mitochondrial homeostasis in RA-FLSs.

The infrapatellar fat pad (IFP) plays a pivotal role in the pathogenesis of knee osteoarthritis (KOA), exhibiting marked histological changes as the disease progresses. However, the intra-tissue variations within KOA-affected IFP remain poorly understood. In this study, we examined IFP tissues from KOA patients at different disease stages, assessing inflammatory damage through histological evaluation via H&E staining. Based on the extent of tissue damage, we classified IFP regions into inflammatory and non-inflammatory layers. Quantitative PCR (qPCR) and immunohistochemical analyses were then employed to compare the expression of joint damage-associated molecules and immune cell infiltration between these two regions. Our results reveal a pronounced inflammatory response in the IFP tissue adjacent to the synovium (inflammatory layer), while the deeper, non-synovial regions (non-inflammatory layer) showed relatively mild inflammation. Additionally, the inflammatory layer exhibited significantly higher secretion of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-8) and adipokines (Leptin, Adiponectin, and FABP4) compared to the non-inflammatory layer. Notably, B cell infiltration was more prominent in the inflammatory layer than other immune cell types, highlighting its potential role in the progression of KOA. These findings underscore the heterogeneity within the IFP and suggest that localized inflammation, particularly B cell involvement, may contribute to the change of IFP and pathophysiology of KOA.

Background: Interstitial lung disease (ILD) is highly prevalent among systemic sclerosis (SSc) patients and is the leading cause of mortality. This study aims to evaluate the independent and combined value of inflammatory markers, coagulation parameters, and autoantibodies for the presence of SSc-ILD.

Methods: A total of 177 patients with SSc were enrolled in this study, including 116 patients with SSc-ILD and 61 without ILD. Multivariate logistic regression was performed to identify independently associated factors for SSc-ILD. The identification efficiency of individual and combined biomarkers was assessed using receiver operating characteristic curves, with the DeLong test applied to compare differences in area under the curve.

Results: The incidence of dcSSc, Raynaud's phenomenon, and digestive system involvement was significantly higher in the SSc-ILD group. Four stepwise models were constructed, and the results of the full-factor model indicated that elevated NLR (neutrophil to lymphocyte ratio), prolonged PT (prothrombin time), and anti-SCL-70 antibody positivity were independent associated factors for SSc-ILD. The combined model of NLR, PT, and anti-SCL-70 yielded an AUC of 0.879 (95% CI: 0.828-0.930), which was significantly greater than any individual marker (P < 0.001), with a sensitivity of 82.6% and a specificity of 85.0%.

Conclusion: NLR, PT, and anti-SCL-70 antibody together form a triad of independent associated factors for SSc-ILD, demonstrating substantial discriminatory potential when considered as a composite indicator.