Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease  

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作  者:Yi-Long Wang Meng-Ying Zhu Zhe-Feng Yuan Xiao-Yan Ren Xiao-Tong Guo Yi Hua Lu Xu Cong-Ying Zhao Li-Hua Jiang Xin Zhang Guo-Xia Sheng Pei-Fang Jiang Zheng-Yan Zhao Feng Gao 

机构地区:[1]Department of Neurology,Children's Hospital,Zhejiang University School of Medicine,Hangzhou 310052,China [2]Children's Hospital,Zhejiang University School of Medicine,Hangzhou 310052,China [3]Children's Hospital,National Clinical Research Center for Child Health,Zhejiang University School of Medicine,Hangzhou 310052,China

出  处:《World Journal of Pediatrics》2024年第3期259-271,共13页世界儿科杂志(英文版)

基  金:supported by Key Research and Development Plan of Zhejiang Province(2020C03038);The National Natural Science Foundation for Young Scholars of China(81901679);The Natural Science Foundation of Zhejiang Province(LGF19H090020).

摘  要:Background Myelin oligodendrocyte glycoprotein(MOG)antibody-associated disease(MOGAD)is an autoimmune demy-elinating disorder of the central nervous system.Methods Extracted proteins from 34 cerebrospinal fluid(CSF)samples[patients with MOGAD(MOG group,n=12);healthy controls(HC group,n=12);patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases(IND group,n=10)]were processed and subjected to label-free quantitative proteomics.Supervised partial least squares-discriminant analysis(PLS-DA)and orthogonal PLS-DA(O-PLS-DA)models were also performed based on proteomics data.Functional analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and Genomes.An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD.Results Four hundred and twenty-nine DEPs(149 upregulated and 280 downregulated proteins)were identified in the MOG group compared to the HC group according to the P value and fold change(FC).Using the O-PLS-DA model,872 differentially abundant proteins were identified with variable importance projection(VIP)scores>1.Five proteins(gamma-glutamyl hydrolase,cathepsin F,interalpha-trypsin inhibitor heavy chain 5,latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1)overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired.Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades,cell adhesion,axon guidance,and glycosphingolipid biosynthesis compared to the HC group.Conclusion The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

关 键 词:Acute disseminated encephalomyelitis Cerebrospinal fluid Complement cascades Myelin oligodendrocyte glycoprotein-associated disease PROTEOMICS 

分 类 号:R741[医药卫生—神经病学与精神病学]

 

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