Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM) – associated interstitial lung disease (ILD) is poor and heterogeneity. Objectives: The aim of this study was to evaluate prognostic factors and to develop a simple and generally applicable bedside decision tree model for predicting outcomes in patients with anti-MDA5+ DM and to guide treatment. Methods: We analyzed data for 246 anti-MDA5+ DM patients from Myositis Study Group-Jiangsu, a multicenter cohort across eighteen tertiary hospitals in Jiangsu province, from March 2019 to October 2020. The primary end point was all-cause death, and the secondary end point was occurring of rapidly progressive-ILD (rp-ILD). We used a multivariable Cox proportional hazards model to identify the independent prognostic risk factors of death and rp-ILD respectively. A decision-tree prediction model was developed by using data from 10 hospital of southern region (n=163), with validation by using contemporaneous data from northern region (n=83). Results: To assess the risk of rp-ILD, we developed a combined risk score, the CROSS score, that included the following values and scores: C-reactive protein (≤8mg/L, 0; >8mg/L, 3), anti-Ro52 antibody (negative, 0; positive, 4), Sex (Female, 0; Male, 2) and Short course of disease (More than 3 months, 0; Less than 3 months, 2). The mortality risk was identified by the CAR score, including C-reactive protein (≤8mg/L, 0; >8mg/L, 1), Alanine Transaminase (≤50units/L, 0; >50units/L, 1) and rp-ILD (non-rpILD, 0; rp-ILD, 3). We divided patients into three risk groups according to the CROSS score: low, 0 to 3; medium, 4 to 7; and high 8-11. And then Use of a simple decision tree prediction model permitted stratification into three different outcome prediction groups. High-risk patients had significantly higher mortality rates than low- and medium-risk patients in both discovery and validation cohorts (p < 0.0001). Conclusion: The CROSS-CAR decision tree model is easy to evaluate the poor prognostic risk in MDA5+ DM patients during any follow-up period. Unnecessary lung examination, such as chest CT scan and arterial blood gas analysis was avoided in low- and medium- rpILD risk patients. The special ambulance, with red cross sign tagged on car in China, may help to screen the high risk patients and to guide further treatment. Disclosure of Interests: None declared

OBJECTIVES:Rapidly progressive interstitial lung disease (RP-ILD) is a major complication of anti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) with a high mortality rate. The aim of the study is to determine whether serum Krebs von den Lungen-6 (KL-6) could be a prognostic biomarker to predict RP-ILD and prognosis in anti-MDA5+DM patients. METHODS:A total of 21 anti-MDA5+DM patients with RP-ILD and 20 anti-MDA5+DM patients without RP-ILD were retrospectively included in this study. Serum KL-6 concentration (pg/mL) was measured using the latex agglutination test. RESULTS:Serum KL-6 level was higher in RP-ILD patients than those in non-RR-ILD patients (1195.61±872.93 vs. 452.6±465.51 pg/mL, p=0.002). The best cut-off value of KL-6 serum level was 500.9 pg/mL using ROC curve (AUC area = 0.7976, p=0.0011). KL-6 >500.9 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR=56.38, 95% CI 5.51-577.504, p=0.001). Serum KL-6 concentrations were significantly higher in dead patients than those in the survivor group (1209.34±840.55 vs. 592.41±667.76, p=0.0033), and higher KL-6 concentration was also an independent risk factor for all-cause death after adjusting confounders (OR = 21.94, 95% CI 3.3-145.73, p=0.001). Anti-MDA5+DM patients with higher KL-6 level displayed a significantly decreased one-year survival rate, as compared with lower KL-6 level (36.36% vs. 89.47%, p=0.0008). CONCLUSIONS:The serum KL-6 levels reflect severity of lung injury and serve as a clinically useful biomarker in detection and monitoring RP-ILD progression in anti-MDA5+DM patients.

Background: Anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5 + DM) is typically amyopathic and associated with a life-threatening, therapy-resistant, rapidly progressive interstitial lung disease (RP-ILD). Objectives: The present study aims to characterize the prognostic factors and long-term outcome of MDA5 + DM -associated RP-ILD. Methods: A multicenter retrospective study was performed across ten tertiary hospitals in China between January 1, 2018 to December 31, 2019. Results: A total of 238 patients (170 women) with MDA5 + DM enrolled into this retrospective clinical study. The mean age was 53.0 ± 12.2 years. The median follow-up duration was 6.3 ± 12.2 months. Of those 238 anti-MDA5+ patients, ILD is commonly observed in 213 patients, and RP-ILD occurred in 35.29% (84/213) of these patients (RP-ILD defined as progressive dyspnea occurs within 1 month after the onset of respiratory symptoms, and chest radiography or pulmonary function test show progressive interstitial abnormalities). The mortality rate of RP-ILD patients within the 6 months was 58.3% (49/84) in our cohort. Death peaked the first three months after diagnosis, occupying 84.8% (39/46) of died RP-ILD patients. Cox univariate proportional hazard analysis showed that age, gender, disease duration, abnormal laboratory features (LDH, CK, ESR and CRP), anti-Ro52 autoantibody and anti-MDA5 grade were related to the risk of occurrence of RP-ILD in patients with MDA5 + DM. The Cox proportional hazards model identified the disease duration [odds ratio (OR) 0.81 (95% CI 0.68, 0.96), P=0.016] as a protective factor, and anti-Ro52 autoantibody [OR 5.82 (95% CI 1.72, 19.73), P=0.005] as independent risk factors for the occurrence of RP-ILD in MDA5 + DM patients. The 6-month all-cause mortality rate of RP-ILD patients was 58.3% (49/84). Conclusion: Combined with anti-Ro52 in Myositis-specific antibodies was associated with the occurrence and long-term mortality in MDA5 + DM -associated RP-ILD patients. The results suggest poor overall survival among patients with MDA5 + DM -associated RP-ILD. Survival during the first 6 months is crucial for long-term survival. Early recognition and prompt treatment of this high-risk group of MDA5 + DM -associated RP-ILD patients are therefore important. Disclosure of Interests: None declared

Objectives Glucocorticoid-induced TNFR-related (GITR) is a gene coding for a member of the TNF receptor superfamily. After activated by its ligand GITRL, GITR could influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases included rheumatoid arthritis and autoimmune thyroid disease. We previously reported that serum GITRL levels are increased in SLE patients compared with healthy controls (HC)[1]. Here, we tested the levels of GITR and GITRL in serum and labial salivary glands from patients with primary Sjögren’s syndrome (SS), and investigated correlation of their expression levels with clinical and laboratory variables. Methods Serum GITR and GITRL levels in 30 primary SS patients and 30 healthy controls were measured by ELISA. Patients were assessed for clinical and laboratory variables. GITR and GITRL levels in labial salivary glands were detected by immunohistochemistry. Results Primary SS patients had significantly increased serum levels of soluble GITR and GITRL compared with controls [GITR:(5.65±3.43) ng/ml vs. (0.33±0.24) ng/ml, p<0.001; GITRL:(10.90±7.60)ng/ml vs. (0.36±0.28)ng/ml, p<0.001)]. Serum GITR and GITRL levels were positively correlated with IgG and ESR. More lymphocytes infiltration could be detected in SS patients compared to HC by Immunohistochemical analyses. Moreover, the expression levels of GITR in lymphocytic foci of the labial salivary glands from SS patients are higher than those in HC. However, GITRL expression was failed to be detected both in SS patient and HC. Conclusions High serum GITR and GITRL levels in SS patients were associated disease activity variables included IgG and ESR, and the expression of GITR was increased along with more lymphocytes infiltration in labial salivary glands, suggesting an important role of GITR and GITRL in the pathogenesis of primary SS pathogenesis. References Lei Gu, Lingxiao Xu, et al. Correlation of Circulating Glucocorticoid-Induced TNFR-Related Protein Ligand Levels with Disease Activity in Patients with Systemic Lupus Erythematosus. Clin. Dev. Immunol.2012,2012:265868 Disclosure of Interest None Declared