Clinical and experimental rheumatology最新文献

Objectives: Rheumatoid arthritis (RA) is an autoimmune condition linked to alterations in the gut microbiota. This study aims to conduct a comprehensive analysis of the literature on gut microbiota and RA over the past 21 years through bibliometric methods, thereby identifying emerging trends and hotspots, and providing insights for the precision treatment of RA.

Methods: The authors analysed articles on gut microbiota in RA published from 2004 to 2024 based on the Web of Science Core Collection database. Bibliometric methods employed tools such as CiteSpace, VOSviewer, and COOC to conduct visual analyses of countries, institutions, references, and keywords.

Results: 1,267 articles from 80 countries led by China and the United States were included. A notable increase in annual publications reflects the growing interest in this field. Simultaneously, contributions and cooperation of institutions in the field are discussed. Furthermore, co-citation and keyword analysis revealed four research hotspots: 1. specific gut microbiota like Prevotella copri modulating immune responses in RA; 2. dietary interventions regulating gut microbiota as therapeutic approaches for RA; 3. high-throughput sequencing technologies enabling microbiome analysis for diagnostic RA; and 4. probiotics and plant-derived bioactive compounds serving as promising adjunctive therapies for RA management.

Conclusions: The relationship between RA and gut microbiota has been extensively studied. The hotspot of future research may be to further study the pathological mechanism of gut microbiota in RA and how to improve the symptoms of RA patients through dietary therapy and adjustment of the homeostasis of gut microbiota.

Objectives: To describe the cumulative degree of disease-induced damage in patients with immunoglobulin G4-related disease (IgG4-RD) during long-term follow-up.

Methods: A total of 334 patients who were diagnosed with IgG4-RD and followed for over 5 years were included from a prospective cohort, with 99 followed for 10 years. The Chinese IgG4-RD Consortium IgG4-RD Damage Index (DI) was scored at baseline (6 months), 5 years, and 10 years. The total DI scores and the frequencies of damage domains and items were described. The characteristics and treatment regimens of patients in increased damage and stable damage subgroups were compared. The risk factors for damage accrual at 5 years and 10 years were explored.

Results: The DI score increased from 0.89 at baseline to 1.29 at 10 years. The 'pancreatic' (13.4%), 'liver/biliary tree' (7.2%), and 'other' (28.9%) domains presented the greatest degree of damage across the assessments. In the 'other' domain, malignancy and diabetes mellitus were crucial items and increased from 0.3% to 5.1% and from 3.6% to 14.4% within 5 years, respectively. Glucocorticoid side effects were also important damage factors. The risk factors for damage accrual at 5 years were baseline pancreatic involvement (OR 2.11, 95% CI: 1.27-3.50; p=0.004) and relapse frequency (OR 1.40, 95% CI: 1.04-1.89; p=0.028). The risk factor for damage accrual at 10 years was baseline pancreatic involvement (OR 2.89, 95% CI: 1.02-8.16; p=0.045).

Conclusions: The long-term damage caused by IgG4-RD includes organ damage and treatment-related damage. The damage caused by IgG4-RD accumulates over time. Pancreatic damage, malignancy, and diabetes are highlighted. Baseline pancreatic involvement and relapse frequency might predict damage accrual within 5 years. The long-term management of IgG4-RD should aim to preserve organ function while minimising treatment-related damage.

Objectives: Increased expression of type I interferon-induced genes is a hallmark of systemic lupus erythematosus (SLE). Measurement of interferon proteins in plasma has been challenging due to their low abundance. Here we utilise a new high sensitivity assay to evaluate levels of interferon proteins in SLE patients.

Methods: Seven interferon proteins (type I: IFNα1:IFNα13, IFNα2, IFNβ, IFNω; type II: IFNγ; type III: IFNλ1, IFNλ2:IFNλ3) were measured in 266 SLE patients using the NULISAseq Inflammation Panel 250 (Alamar Biosciences). IFN profiles (normal or high) were determined using the 95th percentile threshold in healthy controls for each IFN protein. Their relationship to disease activity and type I interferon-stimulated gene (ISG) scores was assessed.

Results: All seven IFN proteins were significantly increased in SLE patients compared to healthy controls and were higher in patients with anti-Sm, anti-Ro and anti-RNP antibodies. IFNα1:IFNα13, IFNα2 and IFNω strongly correlated with the ISG score whereas IFNβ did not. The median levels of IFNα1:IFNα13, IFNα2, IFNω, IFNλ1 and IFNλ2:IFNλ3 progressively increased with disease activity whereas this was not the case for either IFNβ or IFNγ. The most frequent IFN profiles were high type I+III (35%, n=93); normal levels of all IFN proteins (25%, n=67); high type I only (21%, n=56); and high type I+II+III (13%, n=34). The latter associated with serological activity (low complement and high dsDNA antibody titres) and nephritis.

Conclusions: Plasma levels of type I IFN proteins (IFNα1: IFNα13, IFNα2 and IFNω but not IFNβ) and type III IFN proteins (IFNλ1, IFNλ2:IFNλ3) were increased in active disease groups and ISG scores recapitulated this. Longitudinal intra-individual measures of these proteins are needed to explore their utility as biomarkers for SLE disease activity.

Objectives: A randomised controlled trial demonstrated comparable efficacy and safety of a single 6 mL intra-articular (IA) injection of 2.5% polyacrylamide hydrogel (2.5% iPAAG) versus hyaluronic acid (HA) over one year in adults with moderate-to-severe knee osteoarthritis (OA). This study evaluated the long-term effectiveness and safety of 2.5% iPAAG.

Methods: This 3-year extension of a randomised controlled trial (RCT) (ClinicalTrials.gov Identifier: NCT04045431) followed participants who received a single 6 mL IA injection of 2.5% iPAAG. Outcomes included changes from baseline to year 3 in WOMAC pain, stiffness, and physical function subscales (0-100 scale) and patient global assessment (PGA) of OA impact. Safety was assessed up to year 3.

Results: A total of 119 participants received IA 2.5% iPAAG. After one year, 91 participants (44 females) entered the extension study, and 75 completed 3-years of follow-up. At year 3, the mean change in WOMAC pain was -13.1 (95% CI: -17.9 to -8.4; p<0.0001). Between the 1-year and 3-year visits, fifty adverse events (AEs) were reported by 36 participants (29.8%), none of which were assessed as related to 2.5% iPAAG.

Conclusions: A single 6 mL IA injection of 2.5% iPAAG appears to be safe and effective in providing sustained symptom relief for up to 3 years in individuals with knee OA.

Objectives: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and spondyloarthritis (SpA).

Methods: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) identified potential cases of coexisting SpA and sarcoidosis. Inclusion criteria were the fulfilment of the current classification criteria both for SpA (ASAS) and sarcoidosis (WASOG).

Results: We identified twenty-three patients (14 females and 9 males) with a mean age of 44 years at diagnosis of SpA and of 45 years at diagnosis of sarcoidosis. Most of the patients fulfilled the ASAS criteria for axial SpA. In 8 patients, sarcoidosis was diagnosed after SpA, in 9 patients sarcoidosis preceded SpA and in 6 patients the diagnoses were concurrent. Within these groups, the HLA*B-27 haplotype was detected in 5 (62%), 2/8 (25%) and 3 (50%) of patients respectively. A median of 2 years (range 1-19) occurred between the diagnosis of the two diseases in the first 2 groups. Lung, skin, and extra-thoracic lymph nodes were the most frequent sarcoidosis manifestations in all 3 groups.

Conclusions: We have characterised 23 patients who fulfilled the current classification criteria for both SpA and sarcoidosis. Therefore, sarcoidosis may coexist with SpA like other systemic autoimmune diseases, and this may be explained by shared pathogenic mechanisms. Since Th17 cells are leading actors in the pathogenesis of both SpA and sarcoidosis, these cells may be the missing link connecting the two diseases.

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: Interleukin 8 (IL-8) is a chemokine responsible for attracting neutrophils to inflammatory foci, facilitating their migration through interactions with adhesion molecules. Although cytokines play an important role in the pathogenesis of systemic erythematosus (SLE), the clinical relevance of circulating IL-8 levels remains uncertain due to technical difficulties in its measurement in serum. Consequently, information linking serum IL-8 concentrations with specific clinical features of SLE is limited. This study aimed to explore the relationship between serum IL-8 levels and disease activity, serological, and cardiovascular features in patients with SLE.

Methods: In this observational and cross-sectional study, a total of 235 patients with SLE were enrolled and underwent comprehensive characterisation, including assessment of autoantibody profiles, disease activity indices (SLEDAI-2K, LLDAS), damage index (SLICC-DI), and remission status (DORIS). Cardiovascular characteristics were also assessed, including lipid profiles, insulin resistance indices, and carotid ultrasound parameters such as plaque presence, intima-media thickness, and arterial stiffness. Serum IL-8 concentrations were quantified using an innovative ultrasensitive technique, the Single Molecule Array (Simoa®). Multivariable linear regression analyses were conducted to examine the associations between circulating IL-8 levels and clinical as well as cardiovascular manifestations of SLE.

Results: Disease activity scores, damage indices, and autoantibody profiles did not show significant associations with IL-8 levels. Regarding cardiovascular factors, IL-8 was inversely associated with total and non-HDL cholesterol levels in the adjusted models. The Systematic Coronary Risk Evaluation 2 (SCORE2) cardiovascular risk score showed a significant positive association with IL-8.

Conclusions: In SLE, IL-8 is not associated with disease activity or autoantibody profile but may contribute mechanistically to dyslipidaemia and accelerated atherosclerosis.