Clinical Rheumatology最新文献

Axial spondyloarthritis (axSpA) is a chronic, inflammatory, immune-mediated disease characterized by inflammation of the axial skeleton, peripheral joints, and entheses. Patients with axSpA often experience a long diagnostic delay, and if left untreated, axSpA can lead to a substantial disease burden and permanent disability. In the US, axSpA is more commonly reported in White individuals than non-White individuals because of its strong association with the HLA-B27 allele, which is more common in White populations and certain Native American tribes. Underrecognition of the disease in non-White patient groups may contribute to underreporting of prevalence, diagnostic delay, undertreatment, and unnecessary disease burden in these patient populations. The goal of this review is to increase awareness and educate healthcare professionals on axSpA in non-White patients by reviewing epidemiology, diagnostic delay, genetic aspects, disease presentation, and treatment disparities among non-White patient populations in the US to promote timely recognition and treatment of axSpA in these patients.

Background: As a chronic joint disease, osteoarthritis (OA) severely impairs patients' quality of life and mobility. The deubiquitinating enzyme USP14 and Cadherin-11 (CDH11) have been implicated in OA pathogenesis. However, the regulatory interplay between them remains poorly defined.

Methods: IL-1β was used to stimulate chondrocytes for in vitro OA model establishment. Bioinformatics database was employed to assess CDH11 expression in OA samples. MTT assay was performed to evaluate cell viability. Protein expression was analyzed via Western blot. Cell apoptosis was detected by flow cytometry. Levels of ROS, GSH, MDA, Fe²⁺, as well as concentrations of TNF-α and IL-6, were measured using respective assay kits.

Results: CDH11 expression was upregulated in OA samples and IL-1β-induced chondrocytes. Moreover, silencing CDH11 promoted cell viability and attenuated cell apoptosis, inflammation, oxidative stress, and ferroptosis. USP14 stabilized CDH11 through deubiquitination, sustaining CDH11-mediated chondrocyte damage. After USP14 knockdown, cell viability was increased, while cell apoptosis, inflammation, oxidative stress and ferroptosis were mitigated. Furthermore, CDH11 overexpression abrogated the effects of USP14 knockdown on IL-1β-stimulated chondrocytes.

Conclusion: USP14 mediates IL-1β-induced chondrocyte injury by stabilizing CDH11 through deubiquitination, highlighting the USP14-CDH11 axis as a potential regulatory pathway in OA-related chondrocyte pathology. Key Points • CDH11 is highly expressed in OA samples and IL-1β-induced chondrocytes.. • Silencing CDH11 inhibits IL-1β-induced cell injury, oxidative stress and ferroptosis, confirming CDH11 as a pro-injury factor for chondrocytes. • USP14 stabilizes CDH11 through deubiquitination. • Overexpression of CDH11 reverses the effects of USP14 knockdown on IL-1-induced chondrocytes.

Methotrexate (MTX) remains the first-line pharmacotherapy for rheumatoid arthritis (RA), yet gastrointestinal (GI) adverse events (AEs) are frequently reported. This systematic review and meta-analysis aimed to estimate the prevalence of GI AEs among RA patients treated with MTX. A comprehensive search of PubMed, Scopus, and Cochrane databases was conducted, including observational and interventional studies reporting GI AEs in adult RA patients receiving MTX. Risk of bias was assessed using the Newcastle-Ottawa Scale, JBI Critical Appraisal Tool, and Cochrane RoB 2 as appropriate. Pooled prevalence estimates with 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-seven studies involving 19,986 participants were included. Nausea and abdominal pain were the most frequently reported AEs, with pooled prevalence of 24.3% (95% CI: 16.7-34.0) and 19.6% (95% CI: 13.9-26.9), respectively. Substantial heterogeneity was observed across studies and persisted after stratification by MTX route or study design. Nine studies reported discontinuation due to GI AEs, with rates ranging from 1.7% to 23.4% and a pooled prevalence of 8.5% (95% CI: 5.0-14.3). Gastrointestinal AEs affect approximately one-fifth of RA patients receiving MTX, with nausea and abdominal pain being the most common symptoms. GI events leading to treatment discontinuation were relatively uncommon. Clinician awareness and timely management of GI AEs are important to prevent nonadherence and optimize MTX therapy.

Objective: The present study investigated the relationship between serum Matrix metalloproteinase-3 (MMP3) levels in Primary Sjögren's syndrome (pSS) patients and disease activity, clinical parameters, and different clinical manifestations of pSS.

Methods: Serum samples were obtained from 77 pSS patients and 77 healthy controls (HC). MMP3 levels were detected using a biochemical analyzer. Disease activity was assessed using the Sjögren's Syndrome Disease Activity Index (SSDAI) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Pearson correlation analysis was employed to evaluate the relationship between MMP3 levels and clinical parameters.

Results: Serum MMP3 levels in pSS patients were significantly elevated compared to HC (P < 0.0001). Serum MMP3 levels were significantly positively correlated with WBC counts (r = 0.564, P < 0.0001), neutrophil counts (r = 0.5225, P < 0.0001), and serum LDH levels (r = 0.459, P < 0.0001). Moreover, MMP3 levels were significantly positively correlated with both SSDAI scores (r = 0.407, P = 0.002) and ESSDAI scores (r = 0.3061, P = 0.0068).

Conclusion: Serum MMP3 levels are significantly elevated in pSS patients and show significant positive correlations with both SSDAI and ESSDAI scores, as well as key inflammatory parameters (WBC, neutrophil counts, LDH). In conclusion, these consistent associations suggest the potential of serum MMP3 as a biomarker for tracking disease activity in pSS. Key Points • Serum MMP3 levels were significantly elevated in pSS patients. • Serum MMP3 levels showed strong associations with disease activity, WBC counts and neutrophil counts. • MMP3 may serve as a biomarker for tracking pSS activity.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system. We describe a case of a 31-year-old male with ankylosing spondylitis who developed optic neuritis and transverse myelitis accompanied by positive anti-MOG antibodies, and subsequently features consistent with systemic lupus erythematosus (SLE), beginning 3 months after initiating adalimumab. Adalimumab was discontinued, and the patient was treated with pulsed intravenous methylprednisolone followed by rituximab with significant improvement in clinical, imaging, and laboratory manifestations of the disease. This case highlights a rare constellation of overlapping autoimmune diseases, with both MOGAD and SLE emerging after anti-TNF antibody exposure in a patient with ankylosing spondylitis.

Objective: In addition to the Human Leukocyte Antigen B*58:01(HLA-B*58:01), several non-genetic factors have been associated with allopurinol hypersensitivity syndrome, particularly severe cutaneous adverse drug reactions (SCAR), which are clinically serious. However, the magnitude of the impact of these non-genetic factors on the development of SCAR remains unclear. This study aimed to develop a non-genetic risk prediction model for predicting allopurinol-induced SCAR.

Methods: This retrospective observational study was performed during the same time period. SCAR cases were collected from tertiary care hospital centers, while the non-SCAR cases were collected from primary and tertiary care hospital centers. Non-genetic factors including sex, age, renal function, concomitant use of diuretics, starting dose of allopurinol, and serum urate (SU) were used for the development of the prediction models.

Results: Of the 23,294 cases, 209 were SCAR and 23,085 were non-SCAR cases. Three risk stratification models were developed. Models 1A and 1B were applied for patients who did not have and had SU level at the time of starting allopurinol, respectively. Model 2 was applied for patients who had all non-genetic risk factors, started allopurinol within 60 days, but had not yet developed SCAR. The area under the receiver operating characteristic curve for Models 1A, 1B, and 2 was 0.73 (95% CI 0.68-0.77), 0.81 (95% CI 0.75-0.87), and 0.83 (95% CI 0.80-0.86), respectively, indicating good discriminative performance.

Conclusions: The developed non-genetic prediction model demonstrated good discriminative performance. This prediction score could assist physicians' decisions in prescribing allopurinol in the areas where HLA-B*58:01 is limited or unavailable. External validation in future studies is warranted. Key Points • A non-genetic risk prediction model for allopurinol-induced Severe Cutaneous Adverse Drug Reactions, NoG-ASCAR Score, is simple to access and apply in real clinical practice. • The performance of the area under the receiver operating characteristic curve for predicting SCAR of each model was good and had an impact on clinical utility. • It could provide confidence to physicians in prescribing allopurinol in the situation where HLA-B*58:01 assessment is limited or unavailable. • The NoG-ASCAR Score should be considered by policymakers when conducting cost-effectiveness analysis prior to recommending routine HLA-B*58:01 testing before allopurinol initiation.

Background: Osteoarthritis (OA) has been linked to obesity, although the specific contribution of visceral fat remains a topic of ongoing investigation. The body roundness index (BRI) has been proposed as a more precise measure of overall and visceral adiposity compared with traditional indices. The potential association between BRI and the risk of OA has not been fully elucidated.

Methods: Data were obtained from 8803 participants in the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression analysis was applied to evaluate the association between BRI and OA risk. Stratified analyses were conducted across different subgroups, and smoothed curve fitting techniques were used to visualize the results.

Results: Weighted logistic regression analysis and smoothed curve fitting demonstrated a U-shaped association between BRI and OA risk, with higher OA risk observed at both low and high extremes of BRI, relative to an inflection point. Stratified analyses indicated that this relationship varied by gender and ethnicity. Women exhibited a stronger association between higher BRI and OA risk compared with men [odds ratio (OR) 1.01 (0.86-1.06) vs. 1.07 (1.03-1.11)]. Lower BRI values appeared to be more protective among women. Minority populations demonstrated higher optimal BRI values compared with Han Chinese populations. No significant modifying effects were identified for other factors beyond gender and ethnicity.

Conclusion: A significant U-shaped relationship was observed between BRI and OA risk, with both low and high BRI values associated with increased risk. The association was particularly evident among women and ethnic minority populations. These findings highlight the importance of monitoring visceral adiposity as a modifiable factor in OA risk management. Key Points • A nonlinear U-shaped association exists between body roundness index (BRI) and osteoarthritis risk, with increased risk at both low and high BRI extremes. • The BRI-osteoarthritis relationship is modified by gender and ethnicity, demonstrating a stronger association in women and ethnic minority populations. • BRI may serve as a superior anthropometric indicator for visceral adiposity, offering a practical tool for identifying individuals at elevated risk for osteoarthritis.

Objective: This study aimed to analyze the trends and disease burden of rheumatoid arthritis (RA) among women of childbearing age (15-49 years) globally from 1992 to 2021, revealing temporal dynamics and regional disparities to provide scientific evidence for epidemiological research and public health policies.

Methods: Based on data from the Global Burden of Disease Study (GBD 2021), this study employed the age-period-cohort (APC) model to analyze trends across different age groups, periods, and birth cohorts. Additionally, a Bayesian model was used to project the disease burden from 2022 to 2040.

Results: From 1992 to 2021, the global number of RA cases increased from approximately 202,000 to 327,000, with the age-standardized incidence rate (ASIR) rising from 15.34 to 16.57 per 100,000, representing an annual net drift of 0.42%. High Socio-demographic Index (SDI) regions had the highest incidence (22.77/100,000 in 2021) but showed stable trends, while low SDI regions had the lowest incidence (7.84/100,000 in 2021) but exhibited faster growth (annual net drift of 0.75%). Middle-low SDI regions experienced the fastest growth in incidence (annual net drift of 1.07%). RA risk increased with age, peaking in the 45-49 age group. India saw a significant rise in RA cases, while China showed a declining trend. By 2040, the number of RA cases was projected to reach approximately 378000, with global ASIR expected to show moderate growth but persistent regional disparities.

Conclusion: This study revealed the complex epidemiological landscape of RA among women of childbearing age, with global incidence continuing to rise, particularly in low- and middle-income regions. It emphasized the importance of region-specific prevention and management strategies to address the growing burden of RA. Key Points • A significant increase in RA cases globally, from approximately 202,000 in 1992 to 327,000 in 2021, with an age-standardized incidence rate (ASIR) rising from 15.34 to 16.57 per 100,000. • Regional disparities in RA burden, with high Socio-demographic Index (SDI) regions showing the highest incidence (22.77/100,000 in 2021) but stable trends, while low and middle-low SDI regions exhibit the fastest growth (annual net drift of 0.75% and 1.07%, respectively). • Age-specific patterns, with RA risk peaking in the 45-49 age group.Projections indicating a continued rise in RA cases, reaching approximately 378000 by 2040, with persistent regional disparities. • This study highlights the complex epidemiological landscape of RA among women of childbearing age, emphasizing the need for region-specific prevention and management strategies to address the growing burden, particularly in low- and middle-income regions.

Objective: This study aimed to elucidate the role of neuronaI precursor cell-expressed developmentally down-regulated 4-like (NEDD4L), a developmentally downregulated E3 ubiquitin ligase, in rheumatoid arthritis (RA).

Methods: Serum NEDD4L levels in RA patients (during both stable and active disease stages) and healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was used to analyze NEDD4L expression in synovial tissues from RA patients compared to traumatic control subjects. In animal experiments, the proteasome inhibitor MG-132 was administered to inhibit NEDD4L degradation, and its effects on joint inflammation and bone erosion were evaluated in a collagen-induced arthritis (CIA) rat model. At the cellular level, NEDD4L overexpression and knockdown models were constructed in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). The effects of NEDD4L on RA-FLS proliferation, migration, and invasion were assessed using CCK-8, wound healing and Transwell assays, respectively. Transcriptome analysis of the NEDD4L-knockdown model provided further insights into the associated diseases and pathways. Finally, the impact of NEDD4L on key proteins of the Wnt/β-catenin signaling pathway (DVL2, GSK3β, p-GSK3β, β-catenin) was examined via Western blotting and immunofluorescence, systematically investigating the mechanism of NEDD4L in RA pathogenesis both in vivo and in vitro.

Results: NEDD4L expression was downregulated in the serum and synovial tissues of RA patients. Functional assays demonstrated that NEDD4L knockdown enhanced the proliferative, migratory, and invasive capacities of RA-FLSs and promoted the secretion of the pro-inflammatory cytokines IL-6 and TNF-α, whereas NEDD4L overexpression exerted opposite effects. In CIA rats, MG-132 intervention alleviated joint inflammation and bone destruction, concomitant with restored synovial NEDD4L expression. Mechanistic studies further revealed that NEDD4L influences the biological behavior of RA-FLSs by regulating key components of the Wnt/β-catenin signaling pathway.

Conclusion: NEDD4L modulates the migration, invasion, and pro-inflammatory cytokine secretion of RA-FLSs via the Wnt/β-catenin signaling pathway, suggesting its potential as a therapeutic target for RA. Key Points • NEDD4L knockdown activates Wnt/β-catenin pathway (DVL2, GSK3β, β-catenin). • Promotes IL-6/TNF-α secretion and cell invasiveness. • NEDD4L overexpression shows opposite effects. • Potential therapeutic target for RA.