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ObjectiveThis study aimed to analyze potential biomarkers for systemic sclerosis (SSc) by constructing lncRNA–miRNA–mRNA networks in circulating exosomes (cirexos).Materials and methodsDifferentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in SSc cirexos were screened using high-throughput sequencing and detected with real-time quantitative PCR (RT-qPCR). Differentially expressed genes (DEGs) were analyzed using the DisGeNET, GeneCards, GSEA4.2.3, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Receiver operating characteristic (ROC) curves, correlation analyses, and a double-luciferase reporter gene detection assay were used to analyze competing endogenous RNA (ceRNA) networks and clinical data.ResultsIn this study, 286 DEmRNAs and 192 DElncRNAs were screened, of which 18 DEGs were the same as the SSc-related genes. The main SSc-related pathways included extracellular matrix (ECM) receptor interaction, local adhesion, platelet activation, and IgA production by the intestinal immune network. A hub gene, COL1A1, was obtained by a protein–protein interaction (PPI) network. Four ceRNA networks were predicted through Cytoscape. The relative expression levels of COL1A1, ENST0000313807, and NON-HSAT194388.1 were significantly higher in SSc, while the relative expression levels of hsa-miR-29a-3p, hsa-miR-29b-3p, and hsa-miR-29c-3p were significantly lower in SSc (P < 0.05). The ROC curve showed that the ENST00000313807-hsa-miR-29a-3p-COL1A1 network as a combined biomarker of SSc is more valuable than independent diagnosis, and that it is correlated with high-resolution CT (HRCT), Scl-70, C-reactive protein (CRP), Ro-52, IL-10, IgM, lymphocyte percentage, neutrophil percentage, albumin divided by globulin, urea, and RDW-SD (P < 0.05). Double-luciferase reporter gene detection showed that ENST00000313807 interacts with hsa-miR-29a-3p, which interacts with COL1A1.ConclusionThe ENST00000313807-hsa-miR-29a-3p-COL1A1 network in plasma cirexos represents a potential combined biomarker for the clinical diagnosis and treatment of SSc.

Sjögren’s syndrome (SS) is a systemic autoimmune disease with no efficient treatment, and it is associated with dysregulated immune cells and impaired interleukin (IL)-2 signaling. IL-2 is critical for the development and maintenance of Treg cells. The use of low dose of IL-2 (LDIL-2) in the treatment of autoimmune diseases is promising, but the efficacy and mechanism in SS therapy are still to be confirmed. This study aims to investigate the therapeutic effect of LDIL-2 on SS in NOD (non-obese diabetic) mice. NOD mice (female, 8 weeks old) were randomly assigned into three groups (n = 8). Low dose of IL-2 (LDIL-2), high dose of IL-2 (HDIL-2), and isometric sterile water (control) were administered subcutaneously daily from week 8 to week 16. LDIL-2 administration significantly recovered the reduction in saliva flow and suppressed lymphocyte inflammation of the submandibular glands (SMGs) when compared with those treated with sterile water as controls (p < 0.05). SS related biomarkers including ANA, Anti-SSA/Ro, and Anti-SSB/La also declined (p < 0.05). In the low dose of IL-2 treated group, the proportion of CD4+CD25+Foxp3+Tregs in both spleen and cervical-lymph-node were higher than control mice (p < 0.05). Furthermore, CD4+Bcl-6+PD-1+CXCR5+Tfh cells, CD4+IFN-γ+Th1 cells, and CD4+IL-17A+Th17 cells were significantly reduced in LDIL-2 group (p < 0.05). Analysis of the SMGs biopsies showed significantly decreased inflammation scores after LDIL-2 administration and an increase of Tregs with immunohistochemical staining. Our findings provide in vivo evidence that LDIL-2 was an effective therapeutic intervention for SS observed in NOD mice and may restore immune balance through the promotion of Treg and suppression of germinal center (GC) B cells and effector T cells.

Background: Rapidly progressive interstitial lung disease (RP-ILD) is a fatal complication of dermatomyositis (DM) and clinically amyopathic DM (CADM). The objective of this study was to evaluate risk markers associated with RP-ILD incidence in patients with DM/CADM and to develop a RP-ILD risk prediction (RRP) model.Methods: The clinical records of 229 patients with DM/CADM from Peking University People's Hospital, and 97 patients from four other independent clinical centers were retrospectively reviewed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with later RP-ILD incidence to build a risk score model. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the RRP model.Results: A multiparametric RRP model was established based on weighted clinical features, including fever (yes, 5; no, 0), periungual erythema (yes, 6; no, 0), elevated CRP (yes, 5; no, 0), anti-MDA5 antibody (positive, 8; negative, 0), and anti-Ro-52 antibody (positive, 6; negative, 0). Patients were divided into three risk groups according to the RRP total score: low, 0–9; medium, 10–19; high, 20–30. The C-index and calibration curve of the RRP model showed a promising predictive accuracy on the incidence of RP-ILD.Conclusion: The RRP model might promisingly predict the incidence of RP-ILD in DM/CADM patients to guide early individual treatment and further improve the prognosis of DM/CADM patients.

Objective: This study was conducted to identify the characteristics and prognosis of rapidly progressive interstitial lung disease (RP-ILD) in idiopathic inflammatory myopathy (IIM) and to assess the predictors for poor survival of RP-ILD in IIM.Methods: A total of 474 patients with IIM were enrolled retrospectively according to medical records from Peking University People's Hospital. Clinical and laboratory characteristics recorded at the diagnosis of patients with RP-ILD and chronic ILD (C-ILD) were compared. The Kaplan–Meier estimator and univariate and multivariate analyses were used for data analysis.Results: ILD was identified in 65% (308/474) of patients with IIM. Patients with ILD were classified into two groups based on lung features: RP-ILD (38%, 117/308) and C-ILD (62%, 191/308). RP-ILD resulted in significantly higher mortality in IIM compared with C-ILD (27.4 vs. 7.9%, P < 0.05). In this study, by comparing IIM patients with and without RP-ILD, a list of initial predictors for RP-ILD development were identified, which included older age at onset, decreased peripheral lymphocytes, skin involvement (periungual erythema, skin ulceration, and subcutaneous/mediastinal emphysema), presence of anti-MDA5 antibody, serum tumor markers, etc. Further multivariate Cox proportional hazards model analysis identified that anti-MDA5 positivity was an independent risk factor for mortality due to RP-ILD (P < 0.05), and lymphocytes

Objective: Recent studies on double negative B cells (DN B cells) suggested that they have potential pathogenic roles in systemic lupus erythematosus (SLE). This study aimed to determine the circulating DN B cells in SLE patients and analyzed the clinical significance of this cell subset.Methods: Fifty-seven SLE patients and fifty healthy controls (HCs) were recruited in this study. Among the 57 SLE patients, 25 had lupus nephritis (LN). All patients were followed up for 24 weeks. Peripheral B cell subsets were analyzed by flow cytometry.Results: DN B cells were significantly elevated in the SLE patients, especially in the patients with LN (p < 0.01). DN B showed a positive correlation with 24-h urine protein excretion (24 h-UPE) levels (r = 0.444, p = 0.034) in LN patients, and inversely correlated with evaluated glomerular filtration rate (eGFR) (r = −0.351, p = 0.011). DN B cells had a positive correlation with plasma cells (r = 0.484, p < 0.001) and memory B cells (r = 0.703, p < 0.001). After treatment, decreased DN B cells were associated with LN alleviation (p = 0.002). In the follow-up, the remission rate of LN patients with decreased DN B cells was significantly higher than LN patients with increased DN B cells (83.33 vs. 25.00%, p = 0.030) at week 24.Conclusions: This study suggests that the peripheral DN B cells are positively correlated with the severity of renal damage in LN patients and may potentially be used as a prognostic marker in LN.