Treg/Th17 imbalance plays an essential role in the pathogenesis of asthma. Disordered LncRNAs were observed in asthma, however, whether LncRNAs can regulate the Treg/Th17 balance and its mechanism still needs to be investigated. Microarrays were performed to identify the differentially expressed lncRNAs and microRNAs in peripheral blood CD4 + T cells from patients with asthma and healthy controls. Bioinformatical evidence was used to select candidate lncRNAs and microRNAs which may involve in regulation of Treg/Th17 balance. The function of LncRNA-MEG3 and microRNA-17 on the alteration of the CD4 + T cell population were determined in vitro experiments. Meanwhile, the regulatory effect of LncRNA-MEG3 and microRNA-17 on RORγt or Foxp3 was estimated. The interaction of LncRNA-MEG3 with microRNA-17 was confirmed by dual luciferase reporter assay and RNA pull-down. 25 lncRNAs and 19 microRNAs were selected as candidate genes which differentially expressed in CD4 + T cells from patients with asthma compared with healthy controls and had potential to control Treg/Th17 balance by regulating RORγt or Foxp3. Alternation of LncRNA-MEG3 changed the function and increased the percentage of Th17. LncRNA-MEG3 could regulate the RORγt mRNA and protein level. LncRNA-MEG3 could inhibit the level of microRNA-17 as a competing endogenous RNA (ceRNA). microRNA-17 suppressed Th17 though targeting RORγt directly. LncRNA-MEG3 can sponge microRNA-17 as a ceRNA, thereby regulating RORγt and ultimately affecting Treg/Th17 balance in asthma. The lncRNA/microRNA axis may have potential application in clinical treatment and diagnosis of the disease.

In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P < 0.01) and anti-Jo1 (64.9%, P < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P < 0.05). Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.

Objective: The efficacy of tofacitinib (TOF) in the early diagnosis of melanoma differentiation–associated gene 5 (MDA5)–related interstitial lung disease (ILD) has been described. However, whether TOF exposure is associated with a reduced 1-year mortality rate remains undetermined.Methods: Patients diagnosed with MDA5-ILD receiving TOF or tacrolimus (TAC) treatment were included. A Cox proportional hazards model, which was adjusted for age, sex, smoking history, anti-MDA5 antibody titers, and concurrent use of other steroid-sparing agents, was performed to compare all-cause mortality and to investigate the risk factors predicting 1-year mortality rates in the 2 treatment groups.Results: During the study period, 26 patients were treated with TOF and 35 were treated with TAC. The 6-month (38.5% vs 62.9%;P= 0.03) and 1-year (44.0% vs 65.7%;P= 0.03) mortality rates in the TOF group were significantly lower than those in the TAC group. There were 13 patients diagnosed with rapidly progressive ILD (RP-ILD) in the TOF group and 22 in the TAC group. The majority of deaths occurred in patients with RP-ILD. The 6-month (76.9% vs 95.5%;P= 0.02) and 1-year (84.6% vs 100.0%;P= 0.02) mortality rates of patients with RP-ILD in the TOF group were also lower than those in the TAC group, respectively. The adjusted model showed that TOF exposure was associated with a lower risk for 1-year mortality (hazard ratio 0.44, 95% CI 0.20-0.96;P= 0.04). However, the incidence of adverse events (73.1% vs 74.3%;P> 0.99) and medication discontinuation rates (23.1% vs 14.3%;P= 0.50) in the TOF and TAC groups were similar, respectively.Conclusion: Our observational study showed that TOF use might have a potential effect on improving the outcomes of MDA5-ILD. Future clinical trials are needed to assess the long-term efficacy and tolerability of TOF.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder that is characterized by the abnormal accumulation of surfactant within the alveoli. Alveolar macrophages (AMs) have been identified as playing a pivotal role in the pathogenesis of PAP. In most of PAP cases, the disease is triggered by impaired cholesterol clearance in AMs that depend on granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in defective alveolar surfactant clearance and disruption of pulmonary homeostasis. Currently, novel pathogenesis-based therapies are being developed that target the GM-CSF signaling, cholesterol homeostasis, and immune modulation of AMs. In this review, we summarize the origin and functional role of AMs in PAP, as well as the latest therapeutic strategies aimed at addressing this disease. Our goal is to provide new perspectives and insights into the pathogenesis of PAP, and thereby identify promising new treatments for this disease.

Background. Pulmonary alveolar proteinosis (PAP) is a rare disorder which is characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy has been reported to be a novel therapy for PAP with hypercholesterolemia. We aimed to evaluate the safety and efficacy of oral statin therapy for PAP without hypercholesterolemia. Methods. In a prospective real‐world observational study, 47 PAP patients without hypercholesterolemia were screened. Oral statin was initiated as therapy for these PAP patients with 12 months of follow‐up. Results. Forty PAP patients completed the study. 26 (65%) of 40 PAP patients responded to statin therapy according to the study criteria. Partial pressure of arterial oxygen (PaO2) and percentage of diffusion capacity predicted (DLCO%) significantly increased while disease severity score (DSS) and radiographic abnormalities decreased after 12 months of statin therapy (all p < 0.05). The factors associated with response were higher levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) antibody and baseline total cholesterol/high‐density lipoprotein cholesterol (TC/HDL) (p = 0.015 and p = 0.035, respectively). The area under the receiver operating characteristic curve (AUROC) of dose of atorvastatin for predicting the response to statin therapy for PAP was 0.859 (95% CI: 0.738‐0.979, p < 0.001). The cutoff dose of atorvastatin was 67.5 mg daily with their corresponding specificity (64.3%) and sensitivity (96.2%). No severe side effects were observed during the study. Conclusions. In PAP patients without hypercholesterolemia, statin therapy resulted in improvements in arterial blood gas (ABG) measurement, pulmonary function, and radiographic assessment.

Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early.Methods: This prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model’s performance was assessed in terms of discrimination, calibration, and clinical usefulness.Results: This study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846–0.957), good calibration (Hosmer–Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001).Conclusions: We developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making.