Clinical and experimental rheumatology最新文献

Objectives: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is frequently linked with interstitial lung disease (ILD), especially the rapidly progressive ILD (RP-ILD). We conduct this research to evaluate the efficacy and safety of triple-combination (triple-combo) therapy consisting of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide in treating MDA5+ DM patients with ILD.

Methods: A multicentre longitudinal cohort study involving 115 MDA5+ DM patients from the Nanjing Medical University Myositis Associated ILD (NMMI) cohort was conducted between January 2019 and November 2022. Patients were categorised into triple-combo and non-triple therapy groups, and their outcomes were assessed.

Results: Contrary to expectations, triple-combo therapy did not improve the prognosis for MDA5+ DM patients but was linked to increased mortality rates, especially among those at high risk for RP-ILD.

Conclusions: Our study suggests that triple-combo therapy might not be effective in improving prognosis in MDA5+ DM patients. Further research is needed to establish safer and more effective treatment modalities for this patient population.

Objectives: Human epididymis protein 4 (HE4) inhibits the degradation of type I collagen, thus promoting fibrosis. We aimed to investigate serum HE4 levels in patients with idiopathic inflammatory myopathies (IIMs), as potential biomarker of interstitial lung disease (ILD).

Methods: IIMs patients followed in our centre between June 2020 and January 2023 were enrolled. ILD was detected by high-resolution computed tomography (CT) and pulmonary function tests. Serum HE4 levels were measured in patients and controls. Progressive fibrosing (PF-) ILD was evaluated in patients with available 2-year follow-up (INBUILD criteria).

Resilts: We enrolled 90 consecutive IIMs patients (68% females, mean age 59.5 [52.75- 66.0] years) and 42 healthy, age- and sexmatched controls. ILD was diagnosed in 44 (49%) patients. Serum HE4 levels were higher in IIMs patients than controls: 78.55 [54.6-114.4] vs. 51.05 [41.8-62.8] pmol/L (p=0.001). IIMs-ILD patients had higher levels of HE4 vs. those without ILD (193.7 [78.92-137.42] vs. 58.15 [48.32-79] pmol/L, p<0.0001). Serum HE4 levels correlated inversely with diffusing capacity for carbon monoxide (rho=-0.556, p<0.0001) and total lung capacity (rho=-0.459, p=0.001). Serum HE4 levels were the only variable independently associated with IIMs-ILD in two models of multivariate analysis: OR 1.063 (CI 95% 1.02-1.108), p=0.004, and OR 1.059 (CI 95% 1.020-1.099), p=0.003. PF-ILD was detected in 39.4% of IIMs-ILD patients with available follow-up (33/44), without any significant association with baseline serum HE4 levels.

Conclusions: HE4 might be a useful biomarker in the identification and assessment of ILD in IIMs patients.

Objectives: Dermatomyositis (DM) is frequently associated with interstitial lung disease (ILD); however, the molecular mechanisms underlying this association remain unclear. This study aimed to employ bioinformatics approaches to identify potential molecular mechanisms linking DM and ILD.

Methods: GSE46239 and GSE47162 were analysed to identify common differentially expressed genes (DEGs). These DEGs underwent Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein-protein interaction (PPI) network was constructed to identify hub genes and transcriptional regulators. Potential therapeutic drugs were predicted using the Drug-Gene Interaction Database (DGIDB).

Results: A total of 122 common DEGs were identified between the DM and ILD datasets. These DEGs were significantly enriched in signal transduction, transcriptional regulation, inflammation, and cell proliferation. Key pathways included the NOD-like receptor signalling pathway, cytokine-cytokine receptor interaction, and TNF signalling pathway. PPI network analysis revealed the top 10 hub genes: CD163, GZMB, IRF4, CCR7, MMP9, AIF1, CXCL10, CCL5, IRF8, and NLRP3. Additionally, interactions between hub genes and transcription factors/miRNAs were constructed. Eleven drugs targeting four hub genes (CXCL10, MMP9, GZMB, and NLRP3) were predicted using the DGIDB.

Conclusions: In summary, the study identified 10 key genes involved in the molecular pathogenesis of DM and ILD. Moreover, 11 potential drugs were identified that may offer viable therapeutic options for treating DM and ILD in the future.

Idiopathic inflammatory myopathies (IIM), or myositis, are a heterogeneous group of systemic autoimmune disorders that are associated with significant morbidity and mortality. Conducting high-quality clinical trials in IIM is challenging due to the rare and variable presentations of disease. To address this challenge, the Myositis Clinical Trials Consortium (MCTC) was formed. MCTC is a collaborative international alliance dedicated to facilitating, promoting, coordinating and conducting clinical trials and related research in IIM. This partnership works to advance the discovery of effective evidence-based treatments for IIM by integrating a diverse group of clinical investigators, research professionals, medical centres, patient groups, and industry partners. The Steering Committee, Core Group, and Paediatric Subcommittee of MCTC are comprised of myositis experts and junior investigators from around the world, representing a diversity of genders, geographies, and subspecialties. MCTC works alongside other current myositis organisations to complement existing work by concentrating on the operationalisation of clinical trials. Our pilot Myositis Investigators' Information Survey gathered responses from 173 myositis investigators globally and found considerable variability in proficiency with outcome measures, geographic disparities in patient recruitment, and a significant disconnect between investigators' routine myositis patient load and clinical trial enrolment. MCTC will meet the need to support and diversify myositis clinical trials by facilitating trial planning, feasibility assessments, site selection, and the training and mentoring of junior investigators/centres to establish their readiness for clinical trial participation. Through experienced leadership, strategic collaborations, and interdisciplinary discussions, MCTC will establish standards for IIM clinical trial design, protocols, and outcome measures in myositis.

Objectives: Idiopathic inflammatory myopathy (IIM) is a group of systemic autoimmune diseases characterised by muscle involvement. This study aims to reveal the characteristics of IIM subtypes and explore the molecular mechanisms underlying IIM.

Methods: The STRING database was utilised to construct a protein-protein interaction network of differentially expressed genes obtained from the GSE128470, GSE3112, and GSE39454 datasets. The immune cell infiltration level was assessed by CIBERSORT in polymyositis (PM). Experimental autoimmune myositis (EAM) model mice were constructed for experimental verification. Serum levels of soluble CD44 (sCD44) were measured using enzyme-linked immunosorbent assay.

Results: The upregulated hub gene CD44 was highly expressed in inflammatory cells infiltrating the skeletal muscle of patients with PM and in EAM mice. CD44 was correlated with both M1 macrophages (r=0.57, p<0.0001) and M2 macrophages (r=0.57, p<0.0001) in PM. Additionally, CD44+F4/80+ macrophages in skeletal muscle were increased (p<0.0001) and CD44 showed a stronger association with markers of M1 macrophage in EAM mice. Moreover, serum sCD44 levels were elevated in patients with IIM (p=0.0024), PM (p=0.0332) and dermatomyositis (p=0.0001) notably in the anti-melanoma differentiation-associated gene 5 antibody positive subtype (p=0.0007). sCD44 levels also positively correlated with visual analogue score (r=0.4424, p=0.0013), myositis intention to treat activity index (r=0.3938, p=0.0047), skin damage score (r=0.3796, p=0.0101) and skin activity score (r=0.4625, p=0.0014) in patients with IIM.

Conclusions: This study suggests that macrophages expressing CD44 may be involved in the pathogenesis of PM, and sCD44 could serve as a potential marker for skin damage and activity in IIM.

Objectives: This study aimed to evaluate the clinical significance of pleural effusion in adult patients with idiopathic inflammatory myopathies (IIM).

Methods: We assessed a cohort of 158 consecutive patients with IIM. Clinical features and survival rates were compared between patients with and without pleural effusion.

Results: Of those 158 IIM patients, 28 (17.7%) developed pleural effusion. 125 (79.1%) IIM patients had interstitial lung disease (ILD), 26 (20.8%) of which developed pleural effusion. Notably, pleural effusion was associated with a higher incidence of lower lung zone consolidation, rapidly progressive ILD (RP-ILD) and elevated high-resolution computed tomography (HRCT) score, and could robustly predict RP-ILD independently [HR 7.863 (2.160-28.617), p=0.002] in IIM-ILD patients. IIM patients with pleural effusion presented with increased systemic inflammatory response, including more fever, elevated white blood cell count, neutrophil/lymphocyte ratio, C-reactive protein, and erythrocyte sedimentation rate, alongside reduced lymphocyte percentage. Pleural effusion was also associated with more ILD, lower lung zone consolidation, pericardial effusion and RP-ILD, higher HRCT score, and lower HB and albumin levels in IIM. Except for neutrophil/lymphocyte ratio, ILD and pericardial effusion, other correlative variables were potential predictors of higher mortality in IIM. Furthermore, pleural effusion remained an independent predictor of higher mortality in IIM [HR 5.05 (1.633-15.62), p=0.005].

Conclusions: Pleural effusion showed a significant positive association with severe phenotypes of ILD and was the powerful predictor of RP-ILD in IIM-ILD. Furthermore, pleural effusion could reveal adverse disease phenotypes with higher systemic inflammatory level and predict higher mortality independently in IIM.

Objectives: To investigate the clinical characteristics of pharyngeal and laryngeal lesions in patients with anti-melanoma differentiation-associated gene 5 antibodies-positive dermatomyositis (anti-MDA5-positive DM).

Methods: Serological indicators of 131 anti-MDA5-positive DM patients were analysed. All 35 patients with pharyngeal and laryngeal symptoms underwent electronic laryngoscopy examinations.

Results: Pharyngeal and laryngeal symptoms were observed in 26.7% of anti-MDA5-positive DM patients. Low levels of haemoglobin, albumin, prealbumin, high-density lipoprotein and rapidly progressive interstitial lung disease mainly appeared in patients with pharyngeal and laryngeal involvement compared to those without involvement. However, no significant difference in mortality was found between the two groups. The number of patients with pharyngeal and laryngeal involvement was significantly higher in anti-Ro-52 antibody-positive patients than in anti-Ro-52 antibody-negative patients. Patients with higher serum ferritin levels (1000 ng/ml ≤ serum ferritin ≤ 1500 ng/ml) were more likely to develop pharyngeal and laryngeal involvement compared to those with lower serum ferritin levels (serum ferritin < 500 ng/ml). Electronic laryngoscopy examinations effectively assisted rheumatologists in assessing the conditions of the pharyngeal mucosa, arytenoid area, epiglottis, and vocal cords. Some patients also presented with rare lesions such as pharyngeal posterior wall fistulas, epiglottic ulcers, and vocal cord white lesions.

Conclusions: 1. Pharyngeal and laryngeal lesions are not uncommon in anti-MDA5-positive DM, these patients have poorer nutritional status and more severe lung lesions; 2. Positive anti-Ro-52 antibodies and high serum ferritin levels are closely associated with pharyngeal and laryngeal involvement in anti-MDA5-positive DM; 3. Electronic laryngoscopy plays a crucial role in the diagnosis and evaluation of pharyngeal and laryngeal conditions.