Clinical and experimental rheumatology最新文献

Objectives: The Metabolic Score for Insulin Resistance (METS-IR) is a novel, non-insulin-based marker used to assess insulin resistance and cardiovascular risk in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular disease. This study aimed to calculate METS-IR in a large cohort of patients with SLE and to examine its relationship with disease characteristics and cardiovascular comorbidities.

Methods: A total of 308 patients with SLE were recruited. METS-IR was calculated, and the activity (SLEDAI and SLEDAS) and damage index (SDI) scores, full lipid profile, insulin resistance indices through HOMA2 (Homeostasis Model Assessment) calculation and carotid subclinical atherosclerosis were assessed. A multivariable linear regression analysis was conducted to examine the relationship between METS-IR and clinical as well as laboratory disease characteristics, with a particular focus on cardiovascular comorbidities.

Results: METS-IR was not associated with SLE-related disease duration, activity, or damage. However, C-reactive protein levels, as well as positivity for anticardiolipin IgG and anti-beta2 glycoprotein I IgG antibodies, were independently associated with higher METS-IR values after multivariable analysis. Additionally, after adjusting for covariates, apolipoprotein B and A1 levels, along with the atherogenic index, showed significant positive associations with METS-IR. Furthermore, higher serum insulin and C-peptide levels, as well as HOMA-derived measures of insulin resistance and beta cell function, were positively and significantly correlated with elevated METS-IR.

Conclusions: In patients with SLE, METS-IR remains associated with cardiometabolic parameters, including lipid profile and insulin resistance. However, disease-specific factors such as disease activity and accumulated damage show no association with METS-IR.

Objectives: The role of nucleotide oligomerisation domain (NOD)-like receptor with a caspase activation and recruitment domain 3 (NLRC3) in systemic lupus erythematosus (SLE) remains unclear. This study aims to investigate serum NLRC3 levels and their correlations with disease characteristics in SLE.

Methods: This cross-sectional study included 60 newly diagnosed active SLE patients hospitalised at Meizhou People's Hospital between January 2023 and May 2024. An additional 60 SLE patients in the lupus low disease activity state (LLDAS) and 50 healthy controls (HCs) served as control groups. Clinical data were extracted from electronic medical records. Spearman correlation was used to investigate the relationships between NLRC3 and clinical characteristics. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of NLRC3.

Results: Serum NLRC3 levels in active SLE patients were lower than those in LLDAS SLE patients (p=0.014) and HCs (p=0.004), while no notable difference was observed between LLDAS SLE patients and HCs (p=0.631). Active SLE patients with fever, rash, or haematological involvement showed significantly lower NLRC3 levels (p=0.029 for fever; p=0.034 for rash, and p=0.032 for haematological involvement). NLRC3 levels were negatively correlated with fever, rash, leukopenia, and serum BAFF levels (p=0.028; p=0.033; p=0.028 and p=0.017, respectively); positively linked to complement C3 (p=0.044). ROC analysis showed an AUC of 0.665 (p=0.003) for discriminating active SLE from LLDAS SLE.

Conclusions: Serum NLRC3 levels are significantly reduced in active SLE patients and are associated with clinical disease activity parameters. NLRC3 could be a promising biomarker for active SLE identification.

Objectives: The Src homology phosphatase 2 (SHP2) has been shown to be associated with systemic lupus erythematosus (SLE). However, its role and specific mechanisms in lupus nephritis (LN) remains unknown. In this study, we aimed to explore the efficacy and mechanism of targeting SHP2 for treatment of LN.

Methods: The SHP2 was detected in renal tissues of MRL/lpr mice by western blot and immunohistochemistry. The MRL/lpr mice were divided into control group, PBS group and treatment group. The treatment group received SHP099 (SHP2 inhibitor) intraperitoneally daily for 4 weeks. The lupus-like symptoms and renal histopathological changes of mice in the PBS and SHP099 groups were evaluated. The expression of inflammation and fibrosis-related genes in renal tissues was detected by RT-qPCR. The renal tubular epithelial cell (HK-2) injury was induced by lipopolysaccharide (LPS). The effects of SHP099 and ERK/NF-κB signalling pathway on LPS-treated-HK-2 cells were assessed.

Results: SHP2 was activated in kidney tissues of MRL/lpr mice. After treatment with SHP099, renal pathology was alleviated, inflammation- and fibrosis-related gene expression levels were reduced, and ERK/NF-κB signalling pathway-related protein was reduced in MRL/lpr mice. SHP099 inhibited LPS-induced inflammatory activation in HK-2 cells. SHP099 regulated ERK/NF-κB signalling pathway in HK-2 cells.

Conclusions: Our findings suggested that inhibition of SHP2 mitigated renal tubular epithelial cell injury in LN through regulating the ERK/NF-κB signalling pathway. Our study elucidated the mechanism of the beneficial effects of SHP2 inhibitor on LN and provided a promising therapeutic strategy to treat LN.

Objectives: We aimed to study the course of disease activity and pain over two years in patients with early rheumatoid arthritis who began subcutaneous (SC) or peroral (PO) methotrexate (MTX) as part of their first treatment strategy. Treatment failures and drug survival were analysed.

Methods: Patients who received a new reimbursement for RA between 1.1.2016 to 31.12.2023 were identified in the Reimbursement Register; purchases of DMARDs were available in the Drug Purchase Register. Clinical and demographic data were extracted from the Finnish Rheumatology Quality Register. Locally estimated scatterplot smoothing (LOESS) trajectories were used to illustrate the development of disease activity and pain for two years. Treatment failures, defined as the probability to avoid bDMARDs, were analysed with Cox regression, adjusted for age and sex. The proportion of patients taking MTX at two years were calculated.

Results: From the database, we identified 4,655 patients (mean age 60 years, 64% female, 80% seropositive) who started MTX as part of the initial medication for early RA. MTX SC was purchased by 1076(23.1%) and MTX PO by 3579(76.9%) patients. At baseline, the mean (SD) DAS28 was 3.8(1.2) for MTX SC starters and 3.9(1.2) for MTX PO starters. The trajectories for disease activity and pain were more favourable for two years in patients with initial MTX SC versus PO. The probability (95%CI) to avoid bDMARDs was 0.87(0.85 to 0.89) for MTX SC and 0.91(0.90 to 0.92) for MTX PO starters (p<0.001). At two years, MTX was purchased by 80% and 79% of patients who started with MTX SC versus PO, respectively.

Conclusions: Our study provides real-world evidence of the use MTX SC and PO as part of the first treatment strategy for RA. Starting with MTX, SC may be more favourable for patients, in terms of disease activity and pain, over the following two years.

Systemic lupus erythematosus (SLE) represents a multifaceted autoimmune disorder characterised by widespread organ involvement and abnormal autoantibody production. Its underlying mechanisms are closely related to immune system dysfunction. Recent advancements in immunological research have highlighted the pivotal role of the NLRP3 inflammasome, which acts as a key regulator of both innate and adaptive immunity. This molecular complex has attracted significant attention in SLE studies because it can drive pathological inflammation by modulating key pro-inflammatory cytokines, including IL-1β and IL-18, thereby establishing itself as a critical focus in the investigation of SLE pathogenesis.In this review, we conducted a systematic examination of the structural and functional features of NLRP3 inflammatory vesicles, focused on the mechanism of their interaction with different immune cell populations during the development of SLE, and found that their dysfunctions in different immune cells jointly contributed to the pathological process of SLE. Moreover, potential therapeutic strategies aimed at targeting NLRP3 inflammatory vesicles are discussed to introduce novel concepts to the research and treatment of SLE.

Resveratrol (RS), a non-flavonoid polyphenol, is a well-recognised anti-inflammatory compound of red wine. This narrative review aims to explore the mechanisms underlying its potential antioxidant properties in osteoarthritis (OA), rheumatoid arthritis (RA), spondyloarthritis (SpA), and osteoporosis (OP), as well as its clonal variation in red wine and future perspectives for clinical applications.Although human data remain limited and sometimes controversial, recent studies in animal models have demonstrated that RS can reduce inflammation by interacting with various cellular pathways, including the activation of sirtuins, which regulate oxidative stress and bone density in OA and OP, and modulating gut microbiota, as central inflammatory trigger for SpA and RA.While RS effects and toxicity are dosedependent, its concentration in red wine may vary depending on grape clone selection and maceration time, potentially increasing its levels and associated health benefits. Additionally, pterostilbene, a compound structurally related to RS, has shown greater bioavailability and promising antioxidant effects. The rapid metabolism of RS in the human body remains a limitation for its therapeutic use, which might be improved through combination with other antioxidants such as vitamins C and E, curcumin, and quercetin, offering synergistic anti-inflammatory effects.Moreover, advanced delivery systems, including nanotechnology, have been developed to enhance RS absorption and stability. Continued research is essential to better understand the role of RS and other antioxidants, and to optimise their therapeutic potential in the near future.

Objectives: Evidence on the long-term real-world effectiveness and safety of upadacitinib in TNFi-refractory psoriatic arthritis (PsA) remains limited. Our aim was to evaluate the real-world effectiveness and safety of upadacitinib in PsA patients with prior TNF-inhibitor failure.

Methods: This retrospective study included 47 patients with PsA (mean age 46.7 ± 10.1 years, 59.6% female, mean disease duration 9.8 ± 7.4 years). Patients received upadacitinib 15 mg daily and were followed up to 56 weeks. Clinical activity (DAPSA, BASDAI, ASDAS-CRP), ACR responses, PASI, patient-reported outcomes, and adverse events were assessed at baseline, week 12, 24, and 56. Intention-to-treat (ITT) analysis was the primary approach.

Results: Axial involvement was present in 74.5% and enthesitis in 85.1%. At week 12, ITT ACR20/50/70 response rates were 63.8%, 55.3%, and 31.9%, respectively. By week 56, ITT responses were 61.7%, 59.6%, and 51.1%. Significant improvements were also observed in DAPSA, BASDAI, ASDAS-CRP, and PASI scores (all p<0.001), with resolution of enthesitis in most patients. Adverse events occurred in 23.4% of patients, with 10.6% leading to discontinuation. Safety outcomes were consistent with the established profile of upadacitinib, with no new safety signals identified.

Conclusions: Upadacitinib demonstrated sustained efficacy across musculoskeletal and skin domains in PsA patients with prior inadequate response to TNF inhibitors, with a safety profile consistent with previous reports. These findings support its role as an effective treatment option in this difficult-to-treat population.

Objectives: To evaluate nailfold videocapillaroscopy (NVC) findings in paediatric patients with primary Raynaud's phenomenon (pRP) and connective tissue diseases (CTDs). We aimed to assess potential associations between NVC features and clinical/organ involvement in juvenile CTDs.

Methods: NVC was performed in children with pRP and in those with CTDs - including juvenile systemic sclerosis (JSSc), dermatomyositis (JDM), and systemic lupus erythematosus (JSLE) - regardless of RP status, all of whom were followed at our Paediatric Rheumatology Unit. For each patient, 32 images were acquired, and microvascular alterations were analysed and classified as either non-specific or scleroderma patterns (early, active, and late) by two independent observers. A semiquantitative rating scale was adopted to score six capillary abnormalities.

Results: A total of 1600 NVC images from 50 subjects (30 females; mean age 16.4±4.0 years) were evaluated. Scleroderma pattern was significantly more frequent in JSSc vs. pRP (p<0.001) and JDM (p<0.005). Differences in capillaroscopic alterations were observed only between pRP and JSSc for reduced capillary density (p<0.001) and presence of giants (p=0.01). Scleroderma pattern was associated with skin fibrosis (21/25 vs. 0/9; p<0.001) and gastrointestinal involvement (17/25 vs. 1/9; p=0.006), with a trend towards significance for digital ulcers (8/25 vs. 0/9; p=0.07). A significantly higher avascular score was found in patients with interstitial lung disease (ILD) than in those without (0.69±0.51 vs. 0.44±0.38; p=0.048). Indeed, patients with severe reduction of capillary density (≤4 capillaries/millimetre) were more likely to have ILD (5/10 vs. 4/13; p=0.02).

Conclusions: NVC is a valuable tool for differentiating pRP from early juvenile CTDs and may help risk stratification for organ involvement, particularly ILD.

Objectives: The rising prevalence of rheumatic diseases (RD), coupled with a global shortage of rheumatologists, creates significant challenges for timely and accurate diagnosis. This study aimed to develop and evaluate an adaptive machine learning (ML)-based decision support system for facilitating accurate referral of patients with suspected RD to rheumatology clinics.

Methods: Participants attending a rheumatology outpatient clinic for the first time were enrolled in this study. A web-based survey, designed for patient accessibility, collected data on clinical symptoms associated with various rheumatic diseases. At the end of a 6-month follow-up, the rheumatologic disease status (correct referral/unnecessary referral) of the patients was added to the database. A fivefold cross-validation approach was employed to assess model performance. The reported results are the average of these five-fold models, reporting sensitivity, specificity, and area under the curve (AUC).

Results: During the 6-month follow-up period involving 843 participants, 574 were diagnosed with a rheumatologic disease. Overall, 31.9% of participants were found to have been referred unnecessarily. The ML model accurately identified patients who were appropriately referred, achieving a mean AUC of 77.9% (95% CI: 74.9%-80.9%), with a mean sensitivity of 87.1% (95% CI: 84.4%-89.8%), and a mean specificity of 67.8% (95% CI: 62.2%-73.3%) across five folds. The best-performing fold reached an AUC of 81.34% (95% CI: 78.58%-84.22%) with the sensitivity of 81.74% (78.58%- 4.90%) and a specificity of 80.95% (76.26%-85.64%). The addition of four questions (n=245) significantly improved performance metrics, with an AUC of 90.77% (95% CI 87.20-94.34), sensitivity of 89.74% (95% CI 85.14-94.34), and specificity of 92.05% (95% CI 86.05-98.05) for best fold.

Conclusions: This ML-based triage tool demonstrates strong potential for accurately identifying appropriate referrals, reducing unnecessary consultations, and enhancing resource utilisation in rheumatology clinics. Our results show that performance improved through an iterative, patient-feedback-driven refinement process. Future multicentre studies are needed for validation, and collaborative efforts will be essential to maximise its impact.

Objectives: The interleukin (IL)-23/IL-17 pathway is central to the pathogenesis of axial spondyloarthritis (axSpA); however, treatments targeting IL-23 have shown inconsistent effectiveness across spondyloarthritis subtypes. We hypothesised that the IL-23/IL-17 axis varies with disease stage and is modulated by its regulatory counterparts, such as type 1 regulatory T (Tr1) cells.

Methods: Serum levels of IL-17A and IL-23, along with peripheral CD4+IL-17A+ cells, monocytes (CD14+HLA-DR+), dendritic cells (DCs, CD11c+HLA-DR+), and Tr1 cells (CD4+CD49b+LAG3+FoxP3-IL-10+), were analysed in 20 patients with non-radiographic axSpA (nr-axSpA) and 24 with radiographic axSpA (r-axSpA) using enzyme-linked immunosorbent assay and flow cytometry. Additionally, we assessed IL-17A production by healthy CD4+ T cells stimulated by monocyte-derived DCs (moDCs) from patients with axSpA through co-culture experiments.

Results: Patients with nr-axSpA had higher serum IL-23 levels (p=0.014), whereas IL-17A levels were comparable between both groups (p=0.912). Peripheral DCs from the nr-axSpA group produced more IL-23 (p=0.010), while no significant differences were observed in Th17 cell proportions (p>0.05). MoDCs from patients with nr-axSpA induced higher pro-inflammatory cytokine production in healthy CD4+ T cells than those from patients with r-axSpA (p<0.05). Notably, Tr1 cells were reduced in the nr-axSpA group (p=0.025), and IL-10 selectively suppressed IL-23 production by nr-axSpA moDCs (p=0.236).

Conclusions: These findings indicate that IL-23-associated immune activity may be relatively more prominent in early axSpA and that differences in Tr1 cell-related regulation across disease stages could contribute to this pattern.