Use of brain MRI and gene expression atlases to reconstruct the pathophysiology of autoimmune neurological disorders: The proof-of-concept of NMOSD.

IF 4.8 2区 医学 Q1 CLINICAL NEUROLOGY
Multiple Sclerosis Journal Pub Date : 2025-02-01 Epub Date: 2024-12-31 DOI:10.1177/13524585241307154
Laura Cacciaguerra, Loredana Storelli, Elisabetta Pagani, Paolo Preziosa, Sharlota Mesaros, Vittorio Martinelli, Lucia Moiola, Marta Radaelli, Jovana Ivanovic, Olivera Tamas, Jelena Drulovic, Massimo Filippi, Maria A Rocca
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引用次数: 0

Abstract

Background: The understanding of disease pathophysiology is pivotal for tailored treatments. The spatial distribution of brain damage relies on the regional antigen expression and the local balance of susceptibility and protective elements.

Objective: As proof-of-concept, we investigated the spatial association between brain damage and gene expression in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD).

Methods: In this multicenter cross-sectional study, 90 AQP4 + NMOSD patients and 94 age-matched healthy controls underwent a brain magnetic resonance imaging (MRI). We used T2-hyperintense lesion probability maps and white/gray matter atrophy as proxies of inflammation and neurodegeneration. The association with the expression of 266 candidate genes was obtained with the Multimodal Environment for Neuroimaging and Genomic Analysis platform. A functional-enrichment analysis investigated overrepresented biological processes.

Results: In AQP4 + NMOSD, T2-hyperintense lesions were mainly periventricular; atrophy mostly involved the visual pathway. The expression of AQP4 and complement (C4a and C5) was associated with both inflammation and neurodegeneration. Complement activation and regulation/uptake of the insulin-like growth factor were the most relevant enriched pathways. Nonspecific pathways related to DNA synthesis and repair were associated with brain atrophy.

Conclusions: Quantitative MRI and gene expression atlas identified the key elements of AQP4 + NMOSD pathophysiology. This analysis could help in understanding the pathophysiology of antibody-mediated autoimmune disorders.

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来源期刊
Multiple Sclerosis Journal
Multiple Sclerosis Journal 医学-临床神经学
CiteScore
10.90
自引率
6.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Multiple Sclerosis Journal is a peer-reviewed international journal that focuses on all aspects of multiple sclerosis, neuromyelitis optica and other related autoimmune diseases of the central nervous system. The journal for your research in the following areas: * __Biologic basis:__ pathology, myelin biology, pathophysiology of the blood/brain barrier, axo-glial pathobiology, remyelination, virology and microbiome, immunology, proteomics * __Epidemology and genetics:__ genetics epigenetics, epidemiology * __Clinical and Neuroimaging:__ clinical neurology, biomarkers, neuroimaging and clinical outcome measures * __Therapeutics and rehabilitation:__ therapeutics, rehabilitation, psychology, neuroplasticity, neuroprotection, and systematic management Print ISSN: 1352-4585
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