Different immunological mechanisms between AQP4 antibody-positive and MOG antibody-positive optic neuritis based on RNA sequencing analysis of whole blood

Xuelian Chen; Libo Cheng; Ying Pan; Peng Chen; Yidan Luo; Shiyi Li; Wenjun Zou; Ke Wang

doi:10.3389/fimmu.2023.1095966

Different immunological mechanisms between AQP4 antibody-positive and MOG antibody-positive optic neuritis based on RNA sequencing analysis of whole blood

Front Immunol. 2023 Mar 9:14:1095966. doi: 10.3389/fimmu.2023.1095966. eCollection 2023.

Authors

Xuelian Chen^{1

2

3}, Libo Cheng^{1

2

3

4}, Ying Pan^{1

2

3

4}, Peng Chen^{2

3

4}, Yidan Luo^{1

2

3}, Shiyi Li^{2

3

4}, Wenjun Zou^{1

2

3

4}, Ke Wang^{5

6}

Affiliations

¹ Department of Ophthalmology, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu, China.
² Department of Ophthalmology, Jiangnan University Medical Center (JUMC), Wuxi, Jiangsu, China.
³ Department of Ophthalmology, Wuxi No.2 People's Hospital, Wuxi, Jiangsu, China.
⁴ Department of Ophthalmology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
⁵ National Health Commission (NHC) Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
⁶ Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China.

Abstract

Purpose: To compare the different immunological mechanisms between aquaporin 4 antibody-associated optic neuritis (AQP4-ON) and myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) based on RNA sequencing (RNA-seq) of whole blood.

Methods: Whole blood was collected from seven healthy volunteers, 6 patients with AQP4-ON and 8 patients with MOG-ON, and used for RNA-seq analysis. An examination of immune cell infiltration was performed using the CIBERSORTx algorithm to identify infiltrated immune cells.

Results: RNA-seq analysis showed that the inflammatory signaling was mainly activated by TLR2, TLR5, TLR8 and TLR10 in AQP4-ON patients, while which was mainly activated by TLR1, TLR2, TLR4, TLR5 and TLR8 in MOG-ON patients. Biological function identification of differentially expressed genes (DEGs) based on Gene Ontology (GO) term and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, as well as Disease Ontology (DO) analysis, showed that the inflammation in AQP4-ON was likely mediated by damage-associated molecular pattern (DAMP), while which in MOG-ON was likely mediated by pathogen-associated molecular pattern (PAMP). Analysis of immune cell infiltration showed that the proportion of immune cell infiltration was related to patients' vision. The infiltration ratios of monocytes (rs=0.69, P=0.006) and M0 macrophages (rs=0.66, P=0.01) were positively correlated with the BCVA (LogMAR), and the infiltration ratio of neutrophils was negatively correlated with the BCVA (LogMAR) (rs=0.65, P=0.01).

Conclusion: This study reveals different immunological mechanisms between AQP4-ON and MOG-ON based on transcriptomics analysis of patients' whole blood, which may expand the current knowledge regarding optic neuritis.

Keywords: RNA-Seq; aquaporin 4; myelin oligodendrocyte glycoprotein; optic neuritis; toll-like receptors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aquaporin 4 / immunology
Autoantibodies*
Humans
Myelin-Oligodendrocyte Glycoprotein
Optic Neuritis* / diagnosis
Optic Neuritis* / immunology
Sequence Analysis, RNA
Toll-Like Receptors

Substances

Aquaporin 4
Myelin-Oligodendrocyte Glycoprotein
Autoantibodies
Toll-Like Receptors

Grants and funding

This research was financially supported by Major project of Wuxi Commission of Health (Z202014), Young and middle-aged top medical and health talents project of Wuxi Commission of Health (BJ2020031) and Postdoctoral Science Foundation funded project of Jiangsu Province (2021K196B). The funding organization played no role in the study design or its conduct.