Peripheral immune landscape for hypercytokinemia in myasthenic crisis utilizing single-cell transcriptomics.
Innate immunity
Monocyte
Myasthenia gravis
Myasthenic crisis
Single-cell sequencing
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
24 08 2023
24 08 2023
Historique:
received:
16
02
2023
accepted:
07
08
2023
medline:
28
8
2023
pubmed:
25
8
2023
entrez:
24
8
2023
Statut:
epublish
Résumé
Myasthenia gravis (MG) is the most prevalent autoimmune disorder affecting the neuromuscular junction. A rapid deterioration in respiratory muscle can lead to a myasthenic crisis (MC), which represents a life-threatening condition with high mortality in MG. Multiple CD4 We conducted single-cell transcriptomic and immune repertoire sequencing on 33,577 peripheral blood mononuclear cells (PBMCs) from two acetylcholine receptor antibody-positive (AChR +) MG patients during MC and again three months post-MC. We followed the Scanpy workflow for quality control, dimension reduction, and clustering of the single-cell data. Subsequently, we annotated high-resolution cell types utilizing transfer-learning models derived from publicly available single-cell immune datasets. RNA velocity calculations from unspliced and spliced mRNAs were applied to infer cellular state progression. We analyzed cell communication and MG-relevant cytokines and chemokines to identify potential inflammation initiators. We identified a unique subset of monocytes, termed monocytes 3 (FCGR3B In summary, our integrated analysis of single-cell transcriptomics and TCR/BCR sequencing has underscored the role of innate immune activation which is associated with hypercytokinemia in MC. The identification of a specific monocyte cluster that dominates the peripheral immune profile may provide some hints into the etiology and pathology of MC. However, future functional studies are required to explore causality.
Sections du résumé
BACKGROUND
Myasthenia gravis (MG) is the most prevalent autoimmune disorder affecting the neuromuscular junction. A rapid deterioration in respiratory muscle can lead to a myasthenic crisis (MC), which represents a life-threatening condition with high mortality in MG. Multiple CD4
METHODS
We conducted single-cell transcriptomic and immune repertoire sequencing on 33,577 peripheral blood mononuclear cells (PBMCs) from two acetylcholine receptor antibody-positive (AChR +) MG patients during MC and again three months post-MC. We followed the Scanpy workflow for quality control, dimension reduction, and clustering of the single-cell data. Subsequently, we annotated high-resolution cell types utilizing transfer-learning models derived from publicly available single-cell immune datasets. RNA velocity calculations from unspliced and spliced mRNAs were applied to infer cellular state progression. We analyzed cell communication and MG-relevant cytokines and chemokines to identify potential inflammation initiators.
RESULTS
We identified a unique subset of monocytes, termed monocytes 3 (FCGR3B
CONCLUSIONS
In summary, our integrated analysis of single-cell transcriptomics and TCR/BCR sequencing has underscored the role of innate immune activation which is associated with hypercytokinemia in MC. The identification of a specific monocyte cluster that dominates the peripheral immune profile may provide some hints into the etiology and pathology of MC. However, future functional studies are required to explore causality.
Identifiants
pubmed: 37620910
doi: 10.1186/s12967-023-04421-y
pii: 10.1186/s12967-023-04421-y
pmc: PMC10464341
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
564Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
Références
J Invest Dermatol. 2005 Jul;125(1):14-23
pubmed: 15982298
J Autoimmun. 2017 Aug;82:62-73
pubmed: 28549776
Muscle Nerve. 2023 Jul;68(1):8-19
pubmed: 37114503
Cell Mol Life Sci. 2022 Jul 7;79(8):402
pubmed: 35798993
Sci Rep. 2016 Mar 14;6:23002
pubmed: 26972611
Neurology. 2009 May 5;72(18):1548-54
pubmed: 19414721
Nature. 2015 Jul 30;523(7562):612-6
pubmed: 26123020
Ann Clin Transl Neurol. 2021 Apr;8(4):749-762
pubmed: 33616296
Front Neurol. 2020 Dec 23;11:596382
pubmed: 33424747
QJM. 2009 Feb;102(2):97-107
pubmed: 19060020
J Immunol. 2016 Mar 1;196(5):2075-84
pubmed: 26826242
Egypt J Neurol Psychiatr Neurosurg. 2022;58(1):83
pubmed: 35818475
Nat Biotechnol. 2022 Feb;40(2):163-166
pubmed: 35132262
J Neurol. 2022 Jul;269(7):3904-3911
pubmed: 35389099
Neurology. 2020 Jan 21;94(3):e299-e313
pubmed: 31801833
Nat Biotechnol. 2020 Dec;38(12):1408-1414
pubmed: 32747759
Neurol Neuroimmunol Neuroinflamm. 2021 Jan 12;8(2):
pubmed: 33436376
Semin Arthritis Rheum. 2022 Aug;55:152043
pubmed: 35696776
Acta Neuropathol. 2021 Jun;141(6):901-915
pubmed: 33774709
Cell. 2021 Apr 1;184(7):1671-1692
pubmed: 33743212
RMD Open. 2022 Feb;8(1):
pubmed: 35177553
Science. 2017 Apr 21;356(6335):
pubmed: 28428369
Genome Biol. 2018 Feb 6;19(1):15
pubmed: 29409532
Oncotarget. 2017 Jun 16;8(44):76099-76107
pubmed: 29100295
Aging Cell. 2020 Oct;19(10):e13219
pubmed: 32856419
Pulmonology. 2021 Nov-Dec;27(6):486-492
pubmed: 33358260
N Engl J Med. 2020 Dec 3;383(23):2255-2273
pubmed: 33264547
iScience. 2021 Sep 24;24(9):103030
pubmed: 34458692
Muscle Nerve. 2016 Dec;54(6):1030-1033
pubmed: 27121160
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
J Transl Med. 2021 Dec 20;19(1):516
pubmed: 34930325
EBioMedicine. 2020 May;55:102789
pubmed: 32388462
Bioinformatics. 2014 Feb 15;30(4):523-30
pubmed: 24336805
Front Immunol. 2019 Jan 30;9:3124
pubmed: 30761158
Front Immunol. 2021 Jan 27;11:621931
pubmed: 33584721
Clin Immunol. 2022 Dec;245:109184
pubmed: 36372318
Nat Commun. 2021 Feb 17;12(1):1088
pubmed: 33597522
J Med Virol. 2021 Jan;93(1):250-256
pubmed: 32592501
BMC Musculoskelet Disord. 2016 Jul 16;17:293
pubmed: 27424036
Ann Neurol. 2010 Dec;68(6):797-805
pubmed: 21061395
SN Compr Clin Med. 2020;2(9):1407-1411
pubmed: 32838178
Neurology. 2021 Jan 19;96(3):114-122
pubmed: 33144515
BMC Neurol. 2021 Oct 6;21(1):388
pubmed: 34615473
Front Immunol. 2022 Feb 21;13:752189
pubmed: 35265065
Nucleic Acids Res. 2021 Jan 8;49(D1):D613-D621
pubmed: 33211851
Nucleic Acids Res. 2019 Jan 8;47(D1):D721-D728
pubmed: 30289549
Clin Immunol. 2022 Aug;241:109058
pubmed: 35690385
Nat Rev Immunol. 2020 Jun;20(6):355-362
pubmed: 32376901
Neurol Sci. 2022 Apr;43(4):2271-2276
pubmed: 35039987
Nucleic Acids Res. 2016 Jan 4;44(D1):D457-62
pubmed: 26476454
Crit Rev Oncol Hematol. 2013 Oct;88(1):218-30
pubmed: 23602134
Cell Discov. 2021 Sep 14;7(1):85
pubmed: 34521820
Nat Rev Dis Primers. 2019 May 2;5(1):30
pubmed: 31048702
Drugs. 2018 Mar;78(3):367-376
pubmed: 29435915
Front Immunol. 2018 Oct 08;9:2285
pubmed: 30349534
Nat Commun. 2022 Jul 22;13(1):4230
pubmed: 35869073
Science. 2022 May 13;376(6594):eabl5197
pubmed: 35549406
Front Immunol. 2019 Feb 01;10:119
pubmed: 30774631
Front Public Health. 2022 Mar 03;10:822909
pubmed: 35309194
Nucleic Acids Res. 2019 Jan 8;47(D1):D419-D426
pubmed: 30407594
Neurology. 2016 Jul 26;87(4):419-25
pubmed: 27358333
Minerva Ginecol. 2020 Feb;72(1):30-35
pubmed: 32153161
Neurol Sci. 2014 Jul;35(7):1109-14
pubmed: 24497206
Immunol Rev. 2012 Sep;249(1):158-75
pubmed: 22889221
Nat Rev Immunol. 2018 Jan;18(1):35-45
pubmed: 28787399
Lancet Neurol. 2022 Feb;21(2):163-175
pubmed: 35065039