Clinical and experimental rheumatology最新文献

Objectives: This study aimed to develop and validate a risk stratification scale for unfavourable outcomes in adult patients with IgA vasculitis nephritis (IgAVN).

Methods: The derivation cohort in this study was constructed using the existing prognosis data from adult IgAVN cohorts. We extracted the risk factors and their hazard ratios. Only statistically significant risk factors were included in our final risk stratification scale. Then this study validated the risk stratification scale in an external cohort of Chinese patients. The performance of the risk stratification scale was evaluated by the receiver operating characteristic (ROC), calibration, decision, and Kaplan-Meier curves.

Results: Ten cohorts involving 1,814 adult patients with IgAVN were included in this meta-analysis. Serum albumin (ALB), estimated glomerular filtration rate (eGFR), endocapillary hypercellularity (E1), and tubular atrophy/interstitial fibrosis (T1/2) were included in the risk stratification and scored according to their weightings (maximum score: 6.5). An external cohort comprising 133 patients was used to validate the risk stratification scale. The area under the curve (AUC) value of the scoring scale was 0.88 (95%CI: 0.78-0.99), with a sensitivity of 0.79 (95%CI: 0.49-0.95) and specificity of 0.89 (95%CI: 0.82-0.94), at a cut-off value of 3. The calibration, decision, and Kaplan-Meier curves further confirmed the robust performance of the risk stratification scale.

Conclusions: In this study, we established a simple and practical tool to identify adult IgAVN patients at high risk of unfavourable outcomes. Reasonable use of the risk stratification scale can help make early clinical decisions and facilitate the development of precision medicine.

Objectives: To evaluate the clinical response of Janus kinase inhibitors (JAKi) across subtypes of idiopathic inflammatory myopathies (IIM) in a cohort of patients with refractory disease.

Methods: We conducted a retrospective analysis of all adult IIM patients treated with JAKi at our centre. Treatment response was assessed based on changes in muscle strength, serum biomarkers of muscle damage and inflammation, pulmonary function, radiological evolution of interstitial lung disease (ILD) and corticosteroid dosage.

Results: Ten IIM patients who were previously or currently receiving JAKi therapy were identified. Six patients were female and the mean age was 52.7 years (standard deviation [SD] 13.91). Anti-synthetase syndrome was the most common subtype (n=5, 50%). At baseline, median manual muscle test 8 score was 136 (interquartile range [IQR] 25.5) and, after therapy, was 147 (IQR 8), representing a statistically significant increase (p<0.05). Corticosteroid dose reduction was also statistically significant (p<0.05), with the median daily dose decreasing from 10mg to 2.5mg. Additionally, four patients were able to discontinue corticosteroid therapy. In six patients with ILD, diffusion capacity for carbon monoxide improved significantly (p<0.01), from 68.33% (IQR 19.31) to 93% (IQR 7.27). No significant changes were observed in serum inflammatory markers, creatine kinase, forced expiratory volume first second or forced vital capacity.

Conclusions: JAKi therapy appears to be clinically effective, well tolerated, and safe in patients with refractory IIM, with a particular benefit in ILD. The steroid sparing effect was also a major outcome. Future prospective and controlled studies are warranted to confirm these preliminary results and better define the therapeutic potential of JAKi in IIM.

Objectives: Rheumatoid arthritis (RA) is attributed to inflammation and infiltration of immune cells into the inflamed joints. In the synovial fluid (SF), accumulated neutrophils can transdifferentiate into neutrophil-dendritic cell hybrids (N-DCs) and acquire antigen presenting properties. This study aimed to establish the crosstalk, if any, between N-DCs and T lymphocytes in the SF as also assess their potential role in disease sustenance.

Methods: In the SF of patients with RA (n=15), the frequency and activation status of CD4+ and CD8+ T lymphocyte subsets (i.e. memory, naive, central memory or CM, and effector memory or EM) was examined by immunophenotyping (CD4, CD8, CD45RO, CD45RA, CD62L, CD197 and CD69), along with their generation of reactive oxygen species, cytotoxic potential (Granzyme-B), status of pro-inflammatory receptor (CXCR3) and co-stimulation (CD28). Subsequently, the frequency and characterisation of doublets was done by flow cytometry.

Results: In the SF, there was an enhanced proportion of activated CD4+ and CD8+ EM T lymphocytes, that positively correlated with Disease Activity Score DAS28. These EM T lymphocytes demonstrated an enhanced generation of ROS, enhanced cytotoxic potential and were CXCR3+/CD28+. Furthermore, doublets were identified between N-DCs and activated CD4+ EM T lymphocytes, and ex-vivo studies confirmed that their inflammatory milieu facilitated transdifferentiation, activation of T lymphocytes and doublet formation.

Conclusions: In the SF of patients with RA, disease progression was facilitated by formation of doublets between N-DCs and activated effector memory CD4+ T lymphocytes.

Long non-coding RNAs (lncRNAs) are a class of non-coding RNA molecules with a length of more than 200 nucleotides that play key roles in the regulation of gene expression and cell physiology. Studies have shown that lncRNAs can participate in the regulation of the TGF-β/Smad signalling pathway by sponging miRNAs or directly activating Smad protein phosphorylation. The TGF-β/Smad signalling pathway has become a key signalling pathway in osteoarthritis (OA), a traditional degenerative joint disease characterised by an imbalance between cartilage degradation and repair. This review systematically discusses the molecular mechanisms by which lncRNAs regulate OA cartilage repair through the TGF-β/Smad signalling pathway, as well as the regulatory roles of these lncRNAs in inflammatory response, extracellular matrix (ECM) homeostasis, and chondrocyte apoptosis. In addition, the article also summarised the clinical transformation strategies based on lncRNA, including nanoparticle delivery systems (such as exosomes and hydrogels), gene editing technologies (such as CRISPR-Cas9), and precision treatment guided by dynamic biomarkers. Although lncRNA therapy still faces challenges in terms of targeted delivery efficiency and specificity, its potential in early diagnosis and regenerative therapy of OA provides a theoretical basis for the development of novel intervention methods. In the future, combining cutting-edge technologies such as artificial intelligence, single-cell sequencing, and 3D organoids, the application of lncRNA regulatory networks is expected to open up new avenues for OA treatment.

Objectives: The expression of interleukin-1 receptor accessory protein (IL-1RAP) and connections between the anterior insula (AI) and the default mode network (DMN) regions might contribute to the heterogeneity of clinical depression in fibromyalgia (FM). This preliminary observational study provides early insight for a further large-scale study investigating the associations among IL-1RAP expression, AI-DMN connectivity, and clinical depression in FM.

Methods: We recruited seventeen FM patients and conducted clinical assessments, serum proteomic analysis, and magnetic resonance imaging (MRI) of the brain at baseline and 1-year follow-up. We analysed serum IL-1RAP expression from the proteomic analysis. With functional MRI data, we extracted the seed-based functional connectivity (FC) z-scores between the bilateral AI and DMN regions. We performed robust linear regressions among IL-1RAP, AI-DMN FCs, and the Beck Depression Index version II (BDI-II) scores. We performed ridge regressions to examine the impact of IL1RAP and AI-DMN FC interactions on BDI-II scores at baseline and follow-up.

Results: IL-1RAP expression significantly predicted the FC between the bilateral AI and posterior cingulate cortex (PCC). The right AI-PCC FCs negatively affect BDI-II scores. In addition, the negative effects of interactions between the IL-1RAP and the right AI-PCC FCs were significant at baseline but not at one-year follow-up.

Conclusions: IL-1RAP could modulate depression through the AI and PCC connections in FM patients. The findings support further large-scale study to improve the understanding of symptomatic heterogeneity in FM.

Objectives: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome predominantly affecting women, suggesting possible links with reproductive and hormonal factors. Although reproductive history has been associated with various long-term health conditions, its role in FM remains insufficiently explored. This study aimed to investigate the association between parity, age at first pregnancy, and the presence of fibromyalgia among women of reproductive age.

Methods: This cross-sectional observational study included 260 women aged 18-50 years with at least one prior live birth, recruited from Physical Medicine and Rehabilitation, Rheumatology, and Gynaecology Outpatient Clinics between March and December 2024. Demographic, clinical, and reproductive data were collected through structured interviews and medical records. FM diagnosis was based on the 2016 revised criteria of the American College of Rheumatology (ACR) using Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) scores; the Global Symptom Score (GSS) was defined as their sum. Statistical analyses included independent-sample t-tests, chi-square tests, and multivariate logistic regression adjusting for age, body mass index, comorbidities, and educational level.

Results: FM was diagnosed in 104 participants (40%). Women with three or more live births had a significantly higher prevalence of FM compared with those with fewer births (p=0.006). In multivariate analysis, grand multiparity remained independently associated with FM (adjusted OR = 2.46, 95% CI = 1.28-4.72, p=0.006). No significant association was found between age at first pregnancy and FM (p>0.05). FM-diagnosed participants reported significantly higher WPI, SSS, and GSS scores (p=0.001 for all), with strong correlations between WPI and both GSS (r=0.782) and SSS (r=0.472).

Conclusions: Grand multiparity was independently associated with fibromyalgia, suggesting that cumulative hormonal and physiological stress from multiple pregnancies may contribute to chronic pain susceptibility. No association was found between age at first pregnancy and FM. Larger, longitudinal studies are warranted to clarify causal pathways between reproductive history and FM pathogenesis.

Pain is a prevalent symptom experienced by over 80% of patients with idiopathic inflammatory myopathies (IIM). Pain severity ranges between 3 to 4 (out of 10) assessed by various tools in the literature. Myositis-related pain could be affected by underlying disease activity and other biological mechanisms, including muscle and joint inflammation, fasciitis, and central pain sensitisation. Pain is associated with a high disease activity, fatigue and poor functional outcomes among patients with IIM. In this narrative review, we provide an overview of the current knowledge on pain and pain assessment tools in IIM and discuss potential mechanisms underlying myositis-related pain and considerations for management.

Objectives: To investigate gut microbial alteration and their functional consequences in obesity (OB)-related knee osteoarthritis (OA) by integrating microbiome with metabolomic, proteomic, and dietary data.

Methods: Fecal and fasting plasma samples were collected from 91 knee OA patients and 12 OA-free controls, classified into four subgroups based on OB and OA status: 66 OB+OA+, 25 OB-OA+, 5 OB+OA-, and 7 OB-OA-. 16S rRNA gene sequencing was performed to profile gut microbiota. MaAsLin2 modelling was applied, and dietary intake was incorporated into the models. Plasma metabolomics (n=630 metabolites) and proteomics (n=5,416 proteins) were integrated with microbial signatures to assess functional associations.

Results: OB+OA+ patients exhibited significantly lower a- and β-diversity than OB-OA+ (p<0.05). Seventeen microbial taxa were identified to be significantly associated with OB+OA+ (all p<7.65×10-5 after correcting tests for 654 ASVs), and 16 of them remained significant after adjustment for age, sex, antibiotic use, and dietary intake. PICRUSt2-based predictive analysis on these taxa suggested that bile acid biosynthesis was upregulated in OB+OA+ group. These taxa were correlated with 376 metabolites (p<0.05) with enrichment in fatty acid biosynthesis, linoleic/arachidonic acid metabolism, and propanoate metabolism pathways. They were also associated with 146 proteins (p<0.001) with enrichment in PI3K-Akt signalling, ECM-receptor interaction, and lipid/atherosclerosis pathways.

Conclusions: OB+OA+ patients exhibited significant gut microbial dysbiosis associated with systemic metabolic and proteomic alterations relevant to OA pathophysiology. The microbiome-metabolome-proteome axis may provide mechanistic insights into worsened OA outcomes in OB individuals and could inform microbiome-targeted interventions.