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B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease

BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow...

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Autores principales: Zhang, Chao, Zhang, Tian-Xiang, Liu, Ye, Jia, Dongmei, Zeng, Pei, Du, Chen, Yuan, Meng, Liu, Qiang, Wang, Yongjun, Shi, Fu-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409132/
https://www.ncbi.nlm.nih.gov/pubmed/34465614
http://dx.doi.org/10.1212/NXI.0000000000001070
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author Zhang, Chao
Zhang, Tian-Xiang
Liu, Ye
Jia, Dongmei
Zeng, Pei
Du, Chen
Yuan, Meng
Liu, Qiang
Wang, Yongjun
Shi, Fu-Dong
author_facet Zhang, Chao
Zhang, Tian-Xiang
Liu, Ye
Jia, Dongmei
Zeng, Pei
Du, Chen
Yuan, Meng
Liu, Qiang
Wang, Yongjun
Shi, Fu-Dong
author_sort Zhang, Chao
collection PubMed
description BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD. RESULTS: Across the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti–aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19(−) and CD19(+) ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD. DISCUSSION: B cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.
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spelling pubmed-84091322021-09-01 B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease Zhang, Chao Zhang, Tian-Xiang Liu, Ye Jia, Dongmei Zeng, Pei Du, Chen Yuan, Meng Liu, Qiang Wang, Yongjun Shi, Fu-Dong Neurol Neuroimmunol Neuroinflamm Article BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD. RESULTS: Across the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti–aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19(−) and CD19(+) ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD. DISCUSSION: B cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD. Lippincott Williams & Wilkins 2021-08-31 /pmc/articles/PMC8409132/ /pubmed/34465614 http://dx.doi.org/10.1212/NXI.0000000000001070 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Zhang, Chao
Zhang, Tian-Xiang
Liu, Ye
Jia, Dongmei
Zeng, Pei
Du, Chen
Yuan, Meng
Liu, Qiang
Wang, Yongjun
Shi, Fu-Dong
B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
title B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
title_full B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
title_fullStr B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
title_full_unstemmed B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
title_short B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease
title_sort b-cell compartmental features and molecular basis for therapy in autoimmune disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409132/
https://www.ncbi.nlm.nih.gov/pubmed/34465614
http://dx.doi.org/10.1212/NXI.0000000000001070
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