Immune repertoire profiling reveals its clinical application potential and triggers for Neuromyelitis Optica Spectrum Disorders
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Detail(s)
| Original language | English |
|---|---|
| Article number | e200134 |
| Journal / Publication | Neurology: Neuroimmunology and NeuroInflammation |
| Volume | 10 |
| Issue number | 5 |
| Online published | 6 Jul 2023 |
| Publication status | Published - Sept 2023 |
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| DOI | DOI |
|---|---|
| Attachment(s) | Documents
Publisher's Copyright Statement
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| Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85164251507&origin=recordpage |
| Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(0e2bca67-a90b-49c9-a3e0-f403ae245818).html |
Abstract
Background and Objectives Neuromyelitis optica spectrum disorders (NMOSD) is widely recognized as a CNS demyelinating disease associated with AQP4-IgG (T cell–dependent antibody), and its trigger is still unclear. In addition, although the treatment of NMOSD currently can rely on traditional immunosuppressive and modulating agents, effective methods to predict the efficacy of these therapeutics are lacking.
Methods In this study, high-throughput T-cell receptor (TCR) sequencing was performed on peripheral blood from 151 pretreatment patients with AQP4-IgG+ NMOSD and 151 healthy individuals. We compared the TCR repertoire of those with NMOSD with that of healthy individuals and identified TCR clones that were significantly enriched in NMOSD. In addition, we treated 28 patients with AQP4-IgG+ NMOSD with immunosuppressants and followed up for 6 months to compare changes in NMOSD-specific TCRs (NMOSD-TCRs) before and after treatment. Moreover, we analyzed transcriptome and single-cell B-cell receptor (BCR) data from public databases and performed T-cell activation experiments using antigenic epitopes of cytomegalovirus (CMV) to further explore the triggers of AQP4-IgG+ NMOSD.
Results Compared with healthy controls, patients with AQP4-IgG+ NMOSD had significantly reduced diversity and shorter CDR3 length of TCRβ repertoire. Furthermore, we identified 597 NMOSD-TCRs with a high sequence similarity that have the potential to be used in the diagnosis and prognosis of NMOSD. The characterization of NMOSD-TCRs and pathology-associated clonotype annotation indicated that the occurrence of AQP4-IgG+ NMOSD may be associated with CMV infection, which was further corroborated by transcriptome and single-cell BCR analysis results from public databases and T-cell activation experiments.
Discussion Our findings suggest that the occurrence of AQP4-IgG+ NMOSD may be associated with CMV infection. In conclusion, our study provides new clues to uncover the causative factors of AQP4-IgG+ NMOSD and provides a theoretical foundation for treating and monitoring the disease. © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Methods In this study, high-throughput T-cell receptor (TCR) sequencing was performed on peripheral blood from 151 pretreatment patients with AQP4-IgG+ NMOSD and 151 healthy individuals. We compared the TCR repertoire of those with NMOSD with that of healthy individuals and identified TCR clones that were significantly enriched in NMOSD. In addition, we treated 28 patients with AQP4-IgG+ NMOSD with immunosuppressants and followed up for 6 months to compare changes in NMOSD-specific TCRs (NMOSD-TCRs) before and after treatment. Moreover, we analyzed transcriptome and single-cell B-cell receptor (BCR) data from public databases and performed T-cell activation experiments using antigenic epitopes of cytomegalovirus (CMV) to further explore the triggers of AQP4-IgG+ NMOSD.
Results Compared with healthy controls, patients with AQP4-IgG+ NMOSD had significantly reduced diversity and shorter CDR3 length of TCRβ repertoire. Furthermore, we identified 597 NMOSD-TCRs with a high sequence similarity that have the potential to be used in the diagnosis and prognosis of NMOSD. The characterization of NMOSD-TCRs and pathology-associated clonotype annotation indicated that the occurrence of AQP4-IgG+ NMOSD may be associated with CMV infection, which was further corroborated by transcriptome and single-cell BCR analysis results from public databases and T-cell activation experiments.
Discussion Our findings suggest that the occurrence of AQP4-IgG+ NMOSD may be associated with CMV infection. In conclusion, our study provides new clues to uncover the causative factors of AQP4-IgG+ NMOSD and provides a theoretical foundation for treating and monitoring the disease. © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Research Area(s)
Citation Format(s)
Immune repertoire profiling reveals its clinical application potential and triggers for Neuromyelitis Optica Spectrum Disorders. / Miao, Yu; Shi, Ziyan ; Zhang, Wei et al.
In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 10, No. 5, e200134, 09.2023.
In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 10, No. 5, e200134, 09.2023.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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