Clinical and experimental rheumatology最新文献

Objectives: Facet joint osteoarthritis (FJOA) is a degenerative spinal joint condition causing low back pain due to cartilage loss and joint damage. Although some studies have highlighted the importance of pyroptosis or autophagy in cartilage loss under FJOA, no report has identified the biomarkers between the two biological events. This direction demonstrates innovative potential and scientific value. The present study aimed to screen differentially expressed genes (DEGs) linked to pyroptosis and autophagy in FJOA and identify potential biomarkers for FJOA.

Methods: We collected the lumbar facet joints, performed transcriptome sequencing, used a variety of bioinformatics methods to obtain differentially expressed genes (DEGs), and obtained autophagy-related and pyroplosis-related genes (APRGs) from GeneCards database, and then screened out 17 APRGs. Two machine learning methods were used to identify potential biomarkers. Subsequently, clinical sample experiments and cellular experiments were carried out to validate.

Results: We found 7,783 DEGs in samples of FJOA patients and obtained 1,153 autophagy-related genes and 80 pyroptosis-related genes from the GeneCards database. 17 APRGs were screened out from the intersection of the three gene sets. Furthermore, CD274, DDX3X, Caspase-8, and MAPK14 were identified as FJOA characteristic biomarkers. We identified that DDX3X, Caspase-8, and MAPK14 were positively correlated with pyroptosis and autophagy in clinical samples and cell experiments, while CD274 was negatively correlated.

Conclusions: Our study identified CD274, DDX3X, Caspase-8, and MAPK14 in chondrocyte and articular cartilage of articular process with pyroptosis and autophagy in FJOA. Therefore, the four genes are expected to be promising therapeutic targets for FJOA, our findings may provide novel insight in clinic.

Objectives: It has been postulated that the gut microbiota plays an important role in the pathogenesis of spondyloarthritis (SpA). However, cross-sectional studies are limited in their ability to differentiate disease-driven microbial alterations from causative changes. Mendelian randomisation (MR) studies leverage existing genetic associations to investigate causality, offering insights into microbiota-disease associations.

Methods: We conducted a systematic review of all MR studies that evaluated the relationship between the microbiota and axial SpA. Eight studies were identified and reviewed. To look for genetic associations with the microbiota, all of them used the MiBioGen microbiota genome-wide association study (GWAS), with one also using the Dutch Microbiome Project. To find associations between the human genome and disease, various data sources were used, including the published GWAS in ankylosing spondylitis (AS), FinnGen, the UK Biobank, and the Integrative Epidemiology Unit (IEU) Open GWAS project.

Results: MR findings revealed predicted increased abundances of Ruminococcaceae NK4A214 and Verrucomicrobia among others, alongside decreased abundances of Lactobacillaceae, and Rikenellaceae families, as well as the Bacteroides genus. These findings largely support the results from cross-sectional studies of the microbiota in patients with SpA. They suggest that bacteria that disrupt gut barrier function may result in an increased risk of SpA, while the opposite may be true with bacteria such as Alistipes and Bacteroides that may have a protective role.

Conclusions: These results underscore the interplay of genetics, microbiota, and disease. Further research is needed to refine these findings and optimise therapeutic approaches.

Objectives: The interaction of autoantibodies with solid tissues has been extensively studied in systemic lupus erythematosus (SLE), but their interaction with peripheral blood mononuclear cells (PBMCs) remains poorly understood. This study aimed to investigate the effects of autoantibodies on PBMCs in SLE.

Methods: We enrolled 31 SLE patients and 35 healthy controls. Serum antibodies recognising PBMC antigens were assessed by immunoblotting using membrane and cytoplasmic proteins isolated from PBMCs. PBMC antigens were identified by mass spectrometry. The effects of autoantibodies on PBMCs were evaluated using flow cytometry, quantitative real-time PCR (qPCR), and enzyme-linked immunosorbent assay (ELISA).

Results: Antibodies targeting a 55-kDa autoantigen were detected in 48.8% of SLE patients. Mass spectrometry identified SSB (La) protein as one of the potential antigens recognised by these autoantibodies, consistent with the strong association between anti-SSB antibodies and anti-55-kDa antibodies in clinical data. Anti-SSB antibodies exhibited significantly higher binding affinity to PBMCs compared to isotype IgG (23.0% vs. 10.6%, p<0.0001). Furthermore, anti-SSB antibodies promoted the mRNA expression of TNF-α, IL-1β, IL-4, and IL-6 in PBMCs, with IL-6 showing a more than 100-fold increase (p<0.001). The expression of IL-6 was suppressed by resatorvid, a TLR4 inhibitor. CD14-positive monocytes were identified as the primary source of IL-6 in PBMCs stimulated by anti-SSB antibodies.

Conclusions: Our findings demonstrate that anti-SSB antibodies promote cytokine production, particularly IL-6, in monocytes through a TLR4-dependent mechanism.

Objectives: Knee osteoarthritis (OA) continues to be a debilitating global health issue, with effective treatments that have minimal side effects still lacking in modern clinical practice. Cetylated fatty acids (CFAs), a group of esterified fatty acids administered either topically or orally to protect the synovial membrane and stabilise cell membranes, appears to be a promising therapeutic option.

Methods: We conducted a comprehensive search in PubMed, Embase, Cochrane Library, CENTRAL, and Web of Science from the inception until November 2024 to examine the therapeutic effects of CFAs. We included randomised controlled trials (RCTs) with a CFA intervention group compared with a control group that received either a placebo or a non-CFA treatment, as well as pre-post experimental studies that investigate pre-treatment and post-treatment CFA interventions. Subgroup analyses for different forms of CFAs were also conducted.

Results: A total of 5 RCTs and 2 pre-post experimental studies with 357 participants were included. Significant improvements were observed in pain levels (SMD= -0.37, 95% CI= -0.60 to -0.15, p=0.0009), knee ROM (SMD=7.80, 95% CI=4.15 to 11.45, p<0.0001), and physical function (SMD= -0.32, 95% CI= -0.51 to -0.13, p=0.0007) after CFA intervention. No significant difference was observed in the degree of knee stiffness. As for the subgroup analysis, the significant improvements in pain, ROM, and physical function only observed when using oral CFA capsules instead of CFA cream.

Conclusions: Overall, CFAs may improve pain levels, knee ROM, and physical function in patients with knee OA, particularly the oral form. Further research is required to determine the synergic effects as a supplementary regimen, longer term effects, and safety profiles of CFAs in patients with knee OA.

Objectives: Enteropathic arthritis (SpA-IBD) refers to the coexistence of spondyloarthritis (SpA) and inflammatory bowel diseases (IBD). Whether the initial disease manifestation (SpA-first vs. IBD-first) influences clinical phenotypes and treatment outcomes remains uncertain. This study aimed to evaluate potential associations between disease onset and specific musculoskeletal manifestations, as well as to identify predictors of therapeutic multi-failure.

Methods: We conducted a retrospective analysis of patients with SpA-IBD evaluated by both rheumatologists and gastroenterologists at our multidisciplinary ImmunoCenter from March 2022 to March 2024. We compared demographic, clinical, laboratory, and therapeutic characteristics of patients with SpA-first vs. IBD-first presentation. Multivariate logistic regression models were employed to assess associations between disease onset and clinical manifestations, and to identify predictors of therapeutic multi-failure.

Results: Sixty-six patients were included (IBD-first: n=47, 71%; SpA-first: n=19, 29%). Enthesitis was more prevalent in the IBD-first group both at SpA onset (38% vs. 10%, p=0.021) and during follow-up (53% vs. 25%, p=0.034). No significant differences were observed in the frequency of axial (65% vs. 64%) and peripheral (60% vs. 66%) involvement or in laboratory parameters between the two groups. In the multivariate logistic regression, IBD-first presentation was significantly associated with a higher likelihood of developing enthesitis after adjusting for confounders (OR=0.267, 95% CI=0.076-0.942, p=0.040). Regarding treatment outcomes, psoriasis was significantly associated with increased risk of therapeutic multi-failure (OR=6.39, 95% CI=1.60-25.47, p=0.009), whereas other phenotypic features were not significantly predictive.

Conclusions: The significantly higher likelihood of developing enthesitis in IBD-first suggests that distinct disease onset patterns and clinical phenotypes may influence musculoskeletal manifestations and treatment responses in enteropathic arthritis.

Objectives: To evaluate the relationship between patient variables that affect pharmacokinetic variability with glucocorticoid (GC)-related weight gain within the first 12 months of starting prednisone therapy.

Methods: We conducted a retrospective chart review of children aged <18 years diagnosed with rheumatic disease treated with moderate to high-dose prednisone therapy at a single Canadian paediatric academic hospital between January 1, 2010, and December 31, 2020. Using a binary logistic regression, eGFR, initial Body Mass Index (BMI), transaminitis and albumin were evaluated as predictors of GC-related obesity (defined as weight gain greater than 20% and BMI z-score ≥1.88 or >95%ile after 12 months of treatment) was evaluated.

Results: Data for sixty-two patients were included in this analysis with 18 (29%) systemic JIA, (6%) other JIA subtypes, 22 (36%) SLE, and 8 (13%) JDM patients, and the remaining patients diagnosed with connective tissue disease and other inflammatory disorders (n=10, 16%). Eighteen (29%) patients met criteria for GC-induced obesity by 12 months of therapy. Greater BMI z-score prior to initiation of GC-therapy was associated with greater risk of developing GC-induced obesity (OR=2.35, 95%CI=1.39-3.96, p<0.001).

Conclusions: Greater BMI was a predictor of severe GC-related obesity for children with rheumatic disease requiring moderate to high-dose prednisone therapy. Further work is required to determine methods for individualised prednisone dosing, and interventions to mitigate risk for weight gain.

Objectives: This study aimed to investigate factors related to vaccine hesitancy among patients with autoimmune inflammatory rheumatic diseases (AIIRD) attending two Italian Rheumatology Clinics.

Methods: A survey was distributed to AIIRD patients in two Rheumatology Clinics in Milan and Messina. The survey covered demographic information, medical history, vaccination status, sources of vaccine information and attitudes towards vaccines. A multivariate logistic regression was performed to assess the risk factors associated with not being vaccinated.

Results: A total of 371 out of 400 patients responded. Among these, 53.1% reported receiving at least one vaccine among influenza, pneumococcal, meningococcal and zoster, while 18.3% reported no vaccinations and 28.6% were unsure about their vaccination status. Key-factors associated with non-vaccination included reliance on the Internet and social media for vaccine information (p=0.005) and personal knowledge of adverse events (p=0.014). Vaccinated individuals exhibited significantly greater trust in public health agencies (p=0.001), and in vaccine-safety (p=0.004), having an overall more positive attitude towards vaccines (p<0.001). Finally, patients on immunosuppressive therapy were more likely to be vaccinated (OR 2.11, 95% CI 1.05-4.24).

Conclusions: Vaccine hesitancy among AIIRD patients is influenced by several modifiable factors, such as the sources of information they rely on and their level of trust in healthcare professionals. Improving communication between patients and physicians, along with addressing misinformation on digital platforms, could lead to higher vaccine acceptance. Public health initiatives should prioritise targeted interventions that address safety concerns and aim to boost vaccination rates in this high-risk population.

Objectives: COVID-19 infection can trigger a cytokine storm, treatable with immunomodulating therapies similar to those used in rheumatoid arthritis (RA). This study investigated COVID-19 prevalence, hospitalisation, emergency department (ED) visits, and the impact of RA treatment and baseline characteristics on mortality in RA patients.

Methods: RA patients from the Ontario Best Practices Research Initiative (OBRI) were linked to Ontario healthcare records held at the Institute for Clinical Evaluative Sciences (ICES). The study examined COVID-19 infection, ED visits, hospitalisation, and intensive care unit (ICU) admissions between January 1st 2020, and March 31st 2022, and the risk of all-cause mortality before and after the pandemic.

Results: Among 2,969 RA patients, 596 (20.1%) had COVID-19. Of those with COVID-19, 108 (18.1%) were hospitalised or visited ED. Females were more likely to be infected (81.9% vs. 76.5%; adj ORs:1.30; 95% CI: 1.01-1.66). COVID-19 patients were more likely to use biologics (52.5% vs. 46.1%; adj ORs:1.28; 95% CI: 1.04-1.57) or Janus Kinase inhibitors (JAKi) (13.4% vs. 9.5%; adj ORs:1.44; 95% CI: 1.08-1.93). Older age (>80 years) (adj HR: 10.9; 95% CI:6.49-18.2), smoking (adj HR: 1.85; 95% CI:1.41-2.42), and higher disease activity score (adj HR: 1.09; 95% CI:1.00-1.18) were associated with higher all-cause mortality both before and after the COVID-19 pandemic, with stronger associations in the latter. JAKi were negatively associated with increased death before the pandemic (adj HR: 0.55; 95% CI: 0.34-0.91).

Conclusions: COVID-19 was higher in females, younger patients, those with comorbidities, and those using advanced therapies. Compared to pre-pandemic, higher death rates during the pandemic were associated with older age, oral steroid use, smoking, and higher disease activity.