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 

机构地区：[1]NHC Key Laboratory of Glycoconjugates Research,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [2]Zhangjiang Fudan International Innovation Center,Human Phenome Institute,Fudan University,Shanghai 200032,China [3]Department of Rheumatology,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200032,China [4]State Key Laboratory of Genetic Engineering,School of Life Science,Fudan University,Shanghai 200032,China

出　　处：《Phenomics》2023年第5期457-468,共12页表型组学（英文）

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).

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.

关 键 词：DERMATOMYOSITIS Anti-melanoma differentiation-associated gene 5-positive Interstitial lung disease GLYCOSYLATION Matrix assisted laser desorption/ionization time of flight mass spectrometry 

分 类 号：R512.3[医药卫生—内科学]