Ruohan Shi,1,* Yidan Luo,2,3,* Yusheng Chen,1,2,* Xuelian Chen,4 Shiyi Li,5 Ziqing Chen,1 Ke Wang,6,7 Wenjun Zou1,2 

1Department of Ophthalmology, Wuxi No.2 People’s Hospital, Jiangnan University Medical Center(JUMC), Wuxi, Jiangsu, People’s Republic of China; 2Department of Ophthalmology, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Comprehensive Ophthalmology, Wuhan Bright Eye Hospital, Wuhan, Hubei, People’s Republic of China; 4Department of Ophthalmology, PuNan Branch of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5Department of Ophthalmology, Jingjiang People’s Hospital Affiliated to Yangzhou University, Taizhou, Jiangsu, People’s Republic of China; 6National Health Commission (NHC) Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, People’s Republic of China; 7Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wenjun Zou, Department of Ophthalmology, Wuxi No.2 People’s Hospital, Jiangnan University Medical Center (JUMC), Wuxi, Jiangsu, People’s Republic of China, Tel +86-510-6856-3091, Fax +8668562052, Email wenjunzou2022@163.com

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.

Keywords: AQP4 antibody-positive optic neuritis, RNA sequencing, immune response, inflammation, gene expression