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Immune Repertoire Profiling Reveals Its Clinical Application Potential and Triggers for Neuromyelitis Optica Spectrum Disorders.
Miao, Yu; Shi, Ziyan; Zhang, Wei; Zhu, Lin; Tang, Shanshan; Chen, Hongxi; Wang, Xiaofei; Du, Qin; Li, Shuaicheng; Zhang, Ying; Luo, Wenqin; Jin, Xin; Fang, Mingyan; Zhou, Hongyu.
Affiliation
  • Miao Y; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Shi Z; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Zhang W; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Zhu L; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Tang S; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Chen H; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Wang X; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Du Q; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Li S; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Zhang Y; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Luo W; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Jin X; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Fang M; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
  • Zhou H; From the College of Life Sciences (M., X.J.), University of Chinese Academy of Sciences, Beijing; Department of Neurology (Z.S., L.Z., S.T., H.C., X.W., Q.D., Y.Z., W.L., M.F., H.Z.), West China Hospital, Sichuan University, Chengdu; and City University of Hong Kong (W.Z., S.L.), Shenzhen Research I
Neurol Neuroimmunol Neuroinflamm ; 10(5)2023 Sep.
Article in En | MEDLINE | ID: mdl-37414573
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 TCRß 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neuromyelitis Optica / Cytomegalovirus Infections Type of study: Prognostic_studies Limits: Humans Language: En Journal: Neurol Neuroimmunol Neuroinflamm Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neuromyelitis Optica / Cytomegalovirus Infections Type of study: Prognostic_studies Limits: Humans Language: En Journal: Neurol Neuroimmunol Neuroinflamm Year: 2023 Document type: Article