The Different Immune Response Between Onset and Remission of AQP4 Antibody-Positive Optic Neuritis Based on RNA Sequencing of Whole Blood

基于全血RNA测序的AQP4抗体阳性视神经炎发病期和缓解期免疫反应差异

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Abstract

PURPOSE: We aimed to investigate differences in the immune response between the onset and remission phases of AQP4 antibody-positive optic neuritis (AQP4-ON). METHODS: Whole blood samples were collected from 7 healthy volunteers, 6 patients with AQP4-ON in the acute phase and 6 patients with AQP4-ON in the remission phase. Gene expression patterns and immune response pathways associated with the disease phases were identified by sequencing the RNA. CIBERSORTx was used to identify infiltrated immune cells. RESULTS: The enrichment analysis showed that Toll-like receptors, cytokine activity and neutrophil-mediated immune activity were significantly enriched in the acute phase, whereas cell cycle pathway was significantly enriched in the remission phase. TSPO and CDK1 were the core genes in the acute and remission phases, respectively. TSPO expression was positively correlated with M0 macrophages and neutrophils, whereas it was significantly negatively correlated with CD8 T cells (rs=0.66, P=0.0195) and resting natural killer (NK) cells (rs=0.6662, P=0.0180). Best corrected visual acuity (BCVA; logMAR) was positively correlated with activated CD4 memory T cells and resting NK cells and negatively correlated with neutrophils in the acute phase. BCVA (LogMAR) was negatively correlated with monocytes, CD8 T cells, and M0 macrophages and positively correlated with neutrophils in the remission phase. CONCLUSION: The present findings provide valuable insights into different immune responses during different phases of AQP4-ON, which is helpful for patients to develop targeted therapies and personalized treatment strategies.

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