Exploring Gene Expression Profiles in Primary Central Nervous System Vasculitis

Carlo Salvarani, Jonas Paludo, Gene G. Hunder, Stephen M. Ansell, Caterina Giannini, Joseph E. Parisi, John Huston, Matthew J. Koster, Kenneth J. Warrington, Stefania Croci, Robert D. Brown

Research output: Contribution to journalArticlepeer-review


Objective: This study was undertaken to explore the gene expression profile of primary central nervous system vasculitis (PCNSV). Methods: Brain specimens of 4 patients with granulomatous vasculitis (GV), 5 with lymphocytic vasculitis (LV), 4 with amyloid β-related angiitis (ABRA), and 4 normal controls were studied. RNA-sequencing was performed using the Illumina Hiseq-4,000 platform and the Illumina TruSeq Total-RNA library. Student t test and false discovery rate tests were performed for each of the differentially expressed transcripts. Ingenuity Pathway Analysis was used for the pathway expression analysis. CIBERSORT was used to estimate the abundances of different immune cell subsets in the tissues based on gene expression data. Results: Transcripts differentially expressed between PCNSV and normal brain indicated that endosomal, mitochondrial, and ribosome dysfunction, alterations in protein synthesis, and noncoding RNAs might be involved in PCNSV. Pathway analysis revealed the activation of dendritic cell maturation and antigen processing as well as neuroinflammation in PCNSV versus normal brain, whereas oxidative phosphorylation was inhibited. CIBERSORT estimation of immune cell subsets suggested that activated NK cells, M1 macrophages, memory B cells, and follicular helper T cells were likely to be more prevalent in PCNSV samples. Naïve CD4 T cells and monocytes were mainly estimated to be present in GV and ABRA. Plasma cell and γδ T-cell signatures were mainly found in LV and normal brain. GV showed higher levels of genes associated with macrophage activities and T cells. ABRA showed higher levels of long noncoding RNAs and miR-616. LV showed higher levels of genes encoding immunoglobulins. Interpretation: RNA sequencing confirmed PCNSV heterogeneity. ANN NEUROL 2023;93:120–130.

Original languageEnglish (US)
Pages (from-to)120-130
Number of pages11
JournalAnnals of neurology
Issue number1
StatePublished - Jan 2023

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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