皮膚筋炎／多発性筋炎

Childhood-onset rheumatic diseases including Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (jSLE), and Juvenile Dermatomyositis (JDM) could impact growth, but this is not well described within the UK population, particularly over the long term. This study aims to compare the growth patterns of patients with JIA, jSLE, and JDM to those of their peers. This population-based cohort study used primary care data from the Clinical Practice Research Datalink (CPRD) with follow up through to March 2023. Patients diagnosed with JIA, JDM and jSLE, were matched with up to five healthy controls by age, sex and general practice. Age and sex standardised Z-scores were calculated for height and weight. Linear mixed models were used to investigate differences in growth patterns over time. Height measurements from 3736, 182 and 111 children with JIA, jSLE and JDM and weight measurements from 5088, 251 and 144 children with JIA, jSLE and JDM respectively were extracted. JIA patients showed significant baseline differences in height compared to healthy controls (Estimate= -0.061, 95% CI 0.002, 0.121) but this initial reduction was countered by an increased rate of catch up growth over time. Similar patterns were observed in jSLE and JDM, although differences were less consistent and largely confined to specific subgroups. Overall, weight trajectories were broadly similar to those of matched controls across all three diseases. Stratified analyses suggested that growth patterns varied according to age at disease onset, with the clearest differences observed in JIA. Children with JIA, jSLE and JDM demonstrated altered longitudinal growth patterns, with the clearest evidence observed in JIA. Growth trajectories varied according to age at disease onset, particularly during the pre and peri-pubertal period, suggesting that the timing of disease onset may influence long-term growth. These findings support the importance of longitudinal growth monitoring, particularly among children diagnosed during key developmental periods.

BACKGROUND: Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease primarily affecting children, with a female predominance. While muscle fiber inflammation has been extensively investigated, the contribution of the neuromuscular junction (NMJ) and its cellular microenvironment to JDM pathogenesis remains poorly understood. This study aimed to characterize NMJ-related gene expression patterns in JDM to identify potential pathogenic mechanisms and candidate biomarkers. METHODS: An integrated transcriptomic analysis was conducted using two publicly available microarray datasets comprising 40 JDM patients and 22 healthy controls. Twenty-one genes representing five major NMJ functional categories were analyzed: cholinergic transmission, nicotinic acetylcholine receptors, extracellular matrix components, glial markers, and postsynaptic signaling molecules. Differential expression, discriminatory performance, correlation, clustering, and tissue deconvolution analyses were performed. RESULTS: Eighteen of the 21 NMJ-related genes were significantly differentially expressed in JDM (FDR-adjusted p < 0.05). Among these, MBP showed the most pronounced dysregulation and high discriminatory performance (AUC = 0.976, p = 6.10 × 10-16), with marked downregulation associated with increased muscle weakness. Other genes also demonstrated strong discriminatory performance, including AGRN (AUC = 0.941), NID1 (AUC = 0.932), CHRNA1 (AUC = 0.927), NRXN3 (AUC = 0.916), and RYR1 (AUC = 0.913). Correlation analyses revealed disruption of physiological co-expression patterns and the emergence of disease-specific interactions, including altered associations between glial markers and cholinergic components. CHRNA1 expression correlated with both muscle and skin disease activity scores, whereas GFAP expression was associated with disease duration. Clustering analysis indicated a reorganization of NMJ-related gene networks in JDM. Tissue deconvolution suggested that CHRNA1 expression may reflect a shift from inflammatory cell infiltration toward preservation of muscle cell identity. CONCLUSIONS: These findings reveal widespread NMJ-associated transcriptomic remodeling in JDM, involving synaptic, cholinergic, and neuroglial components. The identification of candidate transcriptional biomarkers, particularly MBP and CHRNA1, which show association with disease activity, may warrant further evaluation as potential monitoring tools in independent cohorts. Overall, this study supports a role for NMJ-associated transcriptomic remodeling in JDM pathophysiology and suggests new avenues for mechanistic investigation.

BACKGROUND: Nailfold capillaroscopy is a non-invasive method to visualize altered microcirculation in pediatric rheumatic disease, with potential to aid in diagnostic differentiation and disease monitoring. We used nailfold video capillaroscopy (NVC) and machine learning to identify patterns of capillaroscopic features in juvenile dermatomyositis (JDM) and associations of capillaroscopic features with clinical data. METHODS: NVC features were quantified using automated neural network-based software in 76 individuals, including 18 controls, 33 JDM, 17 childhood-onset systemic lupus erythematosus (cSLE), and 8 overlap myositis (OM) patients. Unsupervised cluster analysis by capillaroscopic features was performed, and clinical features were characterized by cluster. Differences in capillaroscopic features between disease groups were assessed using the Kruskal-Wallis test. For JDM and OM patients, capillaroscopic and clinical feature associations were assessed using Spearman correlation. In 10 treatment-naïve myositis patients (JDM + OM), changes in capillaroscopic features between diagnosis and 3-month follow-up were evaluated. RESULTS: Cluster analysis identified three patient clusters, characterized by the presence of either branched or enlarged capillaries, or absence of these abnormalities. The "branched" cluster was most frequently assigned among JDM and OM and consisted of no controls. The majority of TIF1y+ JDM (4/5) were in the "branched" cluster. In JDM and OM, microhaemorrhage density correlated with disease duration (r = -.45, p = .0033), physician global assessment score (r = .6, p = .0004), lactate dehydrogenase (r = .43, p = .01), von Willebrand factor antigen (r = .51, p = .043), and neopterin (r = .69, p = .01). In 10 myositis patients, microhaemorrhage density decreased while capillary density increased from diagnosis to three months post-treatment. CONCLUSIONS: A branched capillaroscopic pattern was observed more frequently in JDM and OM, particularly TIF1y+ JDM patients within our cohort. Microhaemorrhage density was the most changeable capillaroscopic feature and associated with markers of increased disease activity.

BACKGROUND: Rituximab treatment has shown inconclusive results in clinical trials and observational studies in patients with idiopathic inflammatory myopathies. This study aimed to assess whether complete depletion of distinct B-cell subsets was associated with clinical response in rituximab-treated patients with myositis using highly sensitive flow cytometry (HSFC). METHODS: This single-centre, retrospective cohort study included adults (aged ≥18 years) treated with rituximab who fulfilled the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) classification criteria for idiopathic inflammatory myopathies, followed up at the Leeds Teaching Hospitals NHS Trust (Leeds, UK). HSFC was performed before the first rituximab infusion and at 2 weeks. The primary outcome was a clinical response (at least moderate improvement on the 2016 ACR-EULAR total improvement score) at the first follow-up 4-6 months after infusion. Associations of clinical response with complete HSFC depletion (<0·1 cells per μL) of naive B cells, memory B cells, and plasmablasts versus the conventional flow cytometry cutoff (<5 total B cells per μL) were assessed using multivariable Firth penalised logistic regression. No patients with lived experience were involved in the study. FINDINGS: Between Jan 1, 2015, and Dec 31, 2025, 44 patients with idiopathic inflammatory myopathies were treated with rituximab and had complete datasets. Of these patients, 24 (55%) had dermatomyositis, 12 (27%) had antisynthetase syndrome, five (11%) had immune-mediated necrotising myositis, and three (7%) had polymyositis. 17 (39%) of 44 patients were male, 27 (61%) were female, 35 (80%) were White, and the median age was 45 years (IQR 38-56). Rituximab response occurred in 31 (70%) patients. The total improvement score was higher in responders than non-responders (median 50·0 [IQR 45·0-55·0] vs 17·5 [10·0-30·0]; p<0·0001). At 2 weeks, memory B-cell counts and plasmablast counts were lower in responders than non-responders and complete plasmablast depletion was significantly more frequent in responders (29 [94%] of 31 vs four [31%] of 13; p<0·0001). In multivariable models, higher 2-week plasmablast counts were associated with lower odds of response (odds ratio 0·03 [95% CI 0·00-0·23]), whereas depletion of memory B cells (8·68 [1·13-82·80]) and plasmablasts (25·20 [4·61-214·54]) was associated with response. The conventional flow cytometry cutoff showed no association with response. INTERPRETATION: Complete early B-cell depletion, measured using an early HSFC-based strategy, but not conventional flow cytometry, was associated with rituximab response in patients with idiopathic inflammatory myopathies, supporting further evaluation of a peripheral blood B-cell minimal residual disease framework as a pharmacodynamic and prognostic strategy. These findings could help to select and optimise advanced B-cell depleting strategies in patients with refractory inflammatory myopathies. FUNDING: Leeds National Institute of Health Research Biomedical Research Centre.

BACKGROUND: Anti-MDA5 dermatomyositis is often complicated by interstitial lung disease and early mortality. Peripheral lymphopenia has been linked to poor outcomes, but the routinely measured lymphocyte compartments underlying this signal remain incompletely defined. We used hierarchical flow-cytometric immunophenotyping to characterize the mortality-associated lymphopenic pattern. METHODS: In this exploratory retrospective cohort, we studied 64 adults with anti-MDA5 dermatomyositis who had baseline lymphocyte subset testing and 180-day follow-up. We compared major lymphocyte populations and T-cell differentiation subsets between survivors and non-survivors. Associations with mortality were assessed using ROC, Kaplan-Meier, and Cox regression analyses. RESULTS: Thirteen of 64 patients died by day 180. Non-survivors showed T-cell-dominant lymphopenia, most marked in CD4+ central and effector memory T cells. Median-split Kaplan-Meier analysis showed lower 180-day survival with lower CD4+ memory T-cell counts (log-rank P = 0.00058). Each 1-SD increase in CD4+ memory T-cell count was associated with lower mortality after age adjustment (aHR 0.16, 95% CI 0.04-0.63, P = 0.008). CD4+ memory T-cell count had an AUC of 0.80 (95% CI 0.68-0.91), comparable to total CD4+ T-cell count (AUC 0.78, 95% CI 0.65-0.90). Findings were similar after separate adjustment for LDH or KL-6 and among patients with baseline RP-ILD. CONCLUSIONS: Reduced peripheral CD4+ memory T-cell counts characterized a T-cell-dominant immunophenotype associated with 180-day mortality in anti-MDA5 dermatomyositis. These exploratory findings refine the established CD4+ lymphopenia signal and require validation in independent cohorts.