α2,3-Sialylation with Fucosylation Associated with More Severe Anti-MDA5 Positive Dermatomyositis Induced by Rapidly Progressive Interstitial Lung Disease

作     者：Rongrong Zhang Li Guo Jichen Sha Shuwai Chang Jiangfeng Zhao Kaiwen Wang Jiucun Wang Jianxin Gu Jing Liu Shifang Ren 

作者机构：NHC Key Laboratory of Glycoconjugates ResearchDepartment of Biochemistry and Molecular BiologySchool of Basic Medical SciencesFudan UniversityShanghai 200032China Zhangjiang Fudan International Innovation CenterHuman Phenome InstituteFudan UniversityShanghai 200032China Department of RheumatologyRenji HospitalShanghai Jiao Tong University School of MedicineShanghai 200032China State Key Laboratory of Genetic EngineeringSchool of Life ScienceFudan UniversityShanghai 200032China 

出 版 物：《Phenomics》 (表型组学（英文）)

年 卷 期：2023年第3卷第5期

页      面：457-468页

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：supported by grants from The National Key R&D Program of China(2022YFC3400803) the National Natural Science Foundation of China(32071276) Greater Bay Area Institute of Precision Medicine(IPM2021C005) National Postdoctoral Program for Innovative Talents(BX20190076). 

主　　题：Dermatomyositis Anti-melanoma differentiation-associated gene 5-positive Interstitial lung disease Glycosylation Matrix assisted laser desorption/ionization time of flight mass spectrometry 

摘      要：Dermatomyositis(DM)is a heterogeneous autoimmune disease associated with numerous myositis specific antibodies(MSAs)in which DM with anti-melanoma differentiation-associated gene 5-positive(MDA5+DM)is a unique subtype of DM with higher risk of developing varying degrees of Interstitial lung disease(ILD).Glycosylation is a complex posttranslational modification of proteins associated with many autoimmune diseases.However,the association of total plasma N-glycome(TPNG)and DM,especially MDA5+DM,is still unknown.TPNG of 94 DM patients and 168 controls were analyzed by mass spectrometry with in-house reliable quantitative method called Bionic Glycome method.Logistic regression with age and sex adjusted was used to reveal the aberrant glycosylation of DM and the association of TPNG and MDA5+DM with or without rapidly progressive ILD(RPILD).The elastic net model was used to evaluate performance of glycans in distinguishing RPLID from non-RPILD,and survival analysis was analyzed with N-glycoslyation score by Kaplan-Meier survival analysis.It was found that the plasma protein N-glycome in DM showed higher fucosylation and bisection,lower sialylation(α2,3-notα2,6-linked)and galactosylation than controls.In MDA5+DM,more severe disease condition was associated with decreased sialylation(specificallyα2,3-sialylation with fucosylation)while accompanying elevated H6N5S3 and H5N4FSx,decreased galactosylation and increased fucosylation and the complexity of N-glycans.Moreover,glycosylation traits have better discrimination ability to distinguish RPILD from non-RPILD with AUC 0.922 than clinical features and is MDA5-independent.Survival advantage accrued to MDA5+DM with lower N-glycosylation score(p=3e-04).Our study reveals the aberrant glycosylation of DM for the first time and indicated that glycosylation is associated with disease severity caused by ILD in MDA5+DM,which might be considered as the potential biomarker for early diagnosis of RPILD and survival evaluation of MDA5+DM.