Chenyi Shao’s research while affiliated with Renji Hospital and other places

Background Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome and one of the manifestations of pulmonary involvement in systemic lupus erythematosus (SLE), which is characterized by hemoptysis, diffuse pulmonary infiltrates, and respiratory failure. However, the treatment options for DAH remain limited, and DAH-related studies are needed to explore more effective therapeutic directions for better disease management and improved prognosis. Methods This study utilized the pristane-induced DAH murine model to mimic the pathological process of DAH in patients with SLE. Proteomic analysis was conducted to detect differentially expressed proteins (DEPs) in the plasma of surviving and non-surviving mice, followed by an analysis of biological functions and pathways. The most significant DEP was then confirmed in the plasma of SLE patients with or without DAH and DAH murine model with or without fatal outcomes. Finally, the therapeutic value of haptoglobin (Hp) replacement was validated in a DAH murine model through lung histopathology, RT-qPCR, and survival analysis. Results This study identified 178 DEPs, with 118 upregulated and 60 downregulated DEPs in the non-survival group. Within a set of notable Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, complement and coagulation cascades emerged as the most prominent pathway associated with the process of DAH. Later, the most significant DEP, haptoglobin (Hp), was confirmed to exhibit a significant decrease in the plasma of individuals with SLE-DAH and DAH murine model with poor outcomes by the ELISA test. Finally, compared with the control group, the severity of DAH in the Hp treatment group was alleviated significantly, as manifested by the decreased levels of pro-inflammatory cytokines (IL-6 and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β), and decreased mortality. Conclusion A reduction in plasma Hp levels was observed in SLE-DAH, and the replacement therapy with Hp could alleviate pulmonary hemorrhage and reduce mortality in DAH mice. This study identified Hp as a potential biomarker for its clinical diagnosis and a direction for treatment.

Objectives Interstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5⁺) dermatomyositis (DM) and anti-synthetase syndrome (ASS). Methods Here, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5⁺ DM and ASS groups separately. Results Peripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5⁺ DM and ASS. The multivariate Cox regression analysis revealed that age > 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count < 148 cells/μL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count < 533.2 cells/μL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5⁺ DM, while absolute count of NK cells < 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes < 1.545×10⁹/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin > 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS. Conclusions Patients with anti-MDA5⁺ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD

Objectives: This study investigated the efficacy and safety of abatacept (ABA) in interstitial lung disease (ILD) associated with antisynthetase syndrome (ASS). Methods: Eight patients were identified through retrospective analysis of the medical records of our centre. All patients fulfilled the Solomon criteria and had a disease complicated with ILD. Lung function, imaging, serum markers, clinical evaluation indicators of ILD, peripheral blood cell classification, cytokines, and prednisone doses were analysed. Results: Seven of the eight patients were female. The mean age was 54.4 (standard deviation [SD] 6.0) years. Antibodies against Jo-1, PL-12, and PL-7 were present in three, three, and two patients respectively. At baseline, the mean diffusing lung capacity for carbon monoxide (DLCO) was 53.8% (SD 9.2%), the mean score of King's Brief Interstitial Lung Disease (KBILD) was 40.6 (SD 13.8), the median Krebs Von den Lungen-6 (KL-6) was 1612.5 (interquartile range [IQR] 1180.5-2431.5) U/ml. All patients experienced symptom alleviation after ABA therapy. The mean and median changes in DLCO percentage, KBILD, and KL-6 were 12.3% (p<0.05), 21.4 (p<0.01), and 174.5U/ml (p<0.01), respectively. No obvious adverse events related to ABA were observed during the treatment. Conclusions: Our study offers preliminary, but encouraging, clinical evidence in favour of ABA as a therapy for ASS-ILD. ABA demonstrated favourable effects on ILD and was well-tolerated. Well-designed randomised controlled studies are required to confirm the efficacy and safety of this strategy.