Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies.

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.

Efficacy and safety of abatacept for interstitial lung disease associated with antisynthetase syndrome: a case series.

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.

Noninvasive positive pressure ventilator deteriorates the outcome of pneumomediastinum in anti-MDA5 antibody-positive clinically amyopathic dermatomyositis.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive clinically amyopathic dermatomyositis (CADM) with pneumomediastinum (PNM) is a life-threatening condition. We aim to determine the prognostic factors affecting survival of patients with anti-MDA5 Ab-positive CADM complicated with PNM. METHODS: We retrospectively established a cohort of patients with anti-MDA5 Ab-positive CADM complicated with PNM from April 2013 to July 2019. Demographic data and clinical characteristics from medical records were analyzed and variables were compared between survivors and nonsurvivors. We performed univariate and multivariate survival analyses by Cox regression. Survival curves were depicted by the Kaplan-Meier method. RESULTS: Among 133 patients with anti-MDA5 Ab-positive CADM, 20 were diagnosed with PNM. The cumulative estimated Kaplan-Meier survival rate was 85% at 1 week, 55% at 1 month, and 40% at 1 year. Univariate analysis indicated several factors associated with survival. Worse liver function (AST, p = 0.043; LDH, p = 0.002; TBIL, p = 0.038), higher CRP level (p = 0.044), higher HRCT score (p = 0.022), and using noninvasive positive pressure ventilation (NPPV) (p < 0.01) were associated with poor prognosis. In a multivariate Cox regression model, AST level and using NPPV were indicated to be independent predictors of poor prognosis. CONCLUSION: In this research, we found that the incidence rate of PNM in anti-MDA5 Ab-positive CADM was 15.5%, obviously higher than in classical DM. The application of noninvasive positive pressure ventilator (NPPV) and higher AST level were independent risk factors for survival.Key Points• Anti-MDA5 Ab-positive CADM complicated with PNM is a life-threatening condition with an incidence rate of 15.5%.• The application of NPPV and worse liver function were independent risk factors for survival of anti-MDA5 Ab-positive CADM patients complicated with PNM.