.png){kind=icon}
返回
Exploratory proteomic analysis implicates the alternative complement cascade in primary CNS vasculitis
.png){kind=icon}
OA
AI
DOI：10.1212/WNL.0000000000007850.png)
.png){kind=icon}
.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
Objective To identify molecular correlates of primary angiitis of the CNS (PACNS) through proteomic analysis of CSF from a biopsy-proven patient cohort. Methods Using mass spectrometry, we quantitatively compared the CSF proteome of patients with biopsy-proven PACNS (n = 8) to CSF from individuals with noninflammatory conditions (n = 11). Significantly enriched molecular pathways were identified with a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.5 and concordant Benjamini-Hochberg-adjusted p < 0.05 on DeSeq and t test) were identified as differentially regulated proteins. Results Compared to noninflammatory controls, 283 proteins were differentially expressed in the CSF of patients with PACNS, with significant enrichment of the complement cascade pathway (C4-binding protein, CD55, CD59, properdin, complement C5, complement C8, and complement C9) and neural cell adhesion molecules. A subset of clinically relevant findings were validated by Western blot and commercial ELISA. Conclusions In this exploratory study, we found evidence of deregulation of the alternative complement cascade in CSF from biopsy-proven PACNS compared to noninflammatory controls. More specifically, several regulators of the C3 and C5 convertases and components of the terminal cascade were significantly altered. These preliminary findings shed light on a previously unappreciated similarity between PACNS and systemic vasculitides, especially anti-neutrophil cytoplasmic antibody-associated vasculitis. The therapeutic implications of this common biology and the diagnostic and therapeutic utility of individual proteomic findings warrant validation in larger cohorts.
Keyword:
NERVOUS-SYSTEM VASCULITIS
CEREBROSPINAL-FLUID
PRIMARY ANGIITIS
ATHEROSCLEROSIS
AUTOIMMUNITY
EXPRESSION
INSIGHTS
PATHWAY
AI总结
对已上传原文的论文进行重点信息的提取，主要内容包括：简要概述、研究摘要、背景介绍、关键亮点、图文解析、展望与总结。
期刊
IF:
8.5
论文数:
3.5W
被引数:
9.8W
机构
引用论文
Primary angiitis of the CNS and reversible cerebral vasoconstriction syndrome A comparative study.png)
NEUROLOGY
NEUROLOGYIF8.5
PREAI
分享收藏Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developmentsEMBO JOURNALOAAI
EMBO JOURNALIF8.3
OAAI分享收藏Mechanistic insights into ectodomain shedding: susceptibility of CADM1 adhesion molecule is determined by alternative splicing and O-glycosylationSCIENTIFIC REPORTSOAAI
SCIENTIFIC REPORTSIF3.9
OAAI分享收藏The 120 592 bp IncF plasmid pRSB107 isolated from a sewage-treatment plant encodes nine different antibiotic-resistance determinants, two iron-acquisition systems and other putative virulence-associated functionsMicrobiologyOAAI
MicrobiologyIF0
OAAI分享收藏The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patientsBRAIN
OAAI
BRAINIF11.7
OAAI分享收藏
查看更多内容