The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery.
Genomics
Immune response
Immune system disorder
Immunology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
19 Nov 2021
19 Nov 2021
Historique:
received:
12
07
2021
revised:
10
09
2021
accepted:
26
09
2021
pubmed:
12
10
2021
medline:
12
10
2021
entrez:
11
10
2021
Statut:
ppublish
Résumé
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease.
Identifiants
pubmed: 34632327
doi: 10.1016/j.isci.2021.103215
pii: S2589-0042(21)01183-4
pmc: PMC8487319
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103215Subventions
Organisme : HCRW_
ID : HCRW_HF-19-1595
Pays : United Kingdom
Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
Pediatr Res. 2020 May;87(6):998-1004
pubmed: 31935748
JAMA Pediatr. 2020 Sep 01;174(9):882-889
pubmed: 32320004
JAMA. 2020 Jul 21;324(3):259-269
pubmed: 32511692
J Clin Invest. 2020 Nov 2;130(11):5967-5975
pubmed: 32730233
N Engl J Med. 2020 Jul 23;383(4):334-346
pubmed: 32598831
EClinicalMedicine. 2020 Jun 26;24:100433
pubmed: 32766542
J Pediatr Intensive Care. 2021 Feb 24;11(3):259-264
pubmed: 35928043
Physiol Rev. 2018 Apr 1;98(2):623-639
pubmed: 29412047
BMC Immunol. 2019 Jun 3;20(1):16
pubmed: 31159728
Blood. 2005 Mar 15;105(6):2549-56
pubmed: 15546957
JAMA. 2020 Mar 17;323(11):1061-1069
pubmed: 32031570
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
PLoS One. 2012;7(12):e52406
pubmed: 23285029
Sci Rep. 2017 Mar 27;7(1):447
pubmed: 28348370
Nature. 1999 Oct 14;401(6754):708-12
pubmed: 10537110
Inflamm Res. 2016 Jul;65(7):579-85
pubmed: 27020279
Clin Exp Immunol. 2000 Sep;121(3):566-70
pubmed: 10971526
Front Immunol. 2015 Jan 21;5:674
pubmed: 25653650
Nat Immunol. 2021 Jan;22(1):19-24
pubmed: 33208929
Nat Rev Immunol. 2008 Jan;8(1):34-47
pubmed: 18064051
J Immunol Methods. 2003 Jul;278(1-2):79-93
pubmed: 12957398
Clin Rheumatol. 2016 Jul;35(7):1865-72
pubmed: 25994612
Seizure. 2018 Aug;60:1-7
pubmed: 29857269
Front Immunol. 2020 Dec 18;11:606338
pubmed: 33391273
Nat Commun. 2019 Oct 17;10(1):4706
pubmed: 31624246
Nat Rev Rheumatol. 2021 Feb;17(2):75-76
pubmed: 33349661
Cell. 2020 Nov 12;183(4):968-981.e7
pubmed: 32966765
Korean J Pediatr. 2017 Jul;60(7):216-220
pubmed: 28861112
Proc Natl Acad Sci U S A. 2020 Oct 6;117(40):25018-25025
pubmed: 32943538
Circ Res. 2015 Feb 27;116(5):876-83
pubmed: 25605650
Dev Cell. 2019 Apr 8;49(1):10-29
pubmed: 30930166
Circulation. 2017 Apr 25;135(17):e927-e999
pubmed: 28356445
PLoS One. 2011;6(7):e21800
pubmed: 21789182
Front Pediatr. 2020 Jun 25;8:295
pubmed: 32670996
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nat Rev Rheumatol. 2020 Jul;16(7):391-405
pubmed: 32457494
Mult Scler. 2020 Dec;26(14):1929-1937
pubmed: 31701790
Blood. 2017 Mar 9;129(10):1343-1356
pubmed: 28053192
Inflammation. 2015 Feb;38(1):384-93
pubmed: 25342286
Sci Immunol. 2021 Mar 2;6(57):
pubmed: 33653907
Am J Physiol Lung Cell Mol Physiol. 2011 Aug;301(2):L247-54
pubmed: 21622848
Front Immunol. 2021 Jan 14;11:604512
pubmed: 33584675
Pediatr Res. 2003 Jun;53(6):983-8
pubmed: 12621103
Lancet Infect Dis. 2020 Nov;20(11):e276-e288
pubmed: 32818434
Nat Rev Immunol. 2012 Feb 17;12(3):191-200
pubmed: 22343568
Front Immunol. 2021 Mar 25;12:652470
pubmed: 33841435
Blood. 2011 Aug 4;118(5):e16-31
pubmed: 21653326
Am J Respir Cell Mol Biol. 2018 Apr;58(4):492-499
pubmed: 29141155
Nat Med. 2020 Nov;26(11):1701-1707
pubmed: 32812012
Eur J Pediatr. 2021 Jul;180(7):2019-2034
pubmed: 33599835
Transl Res. 2020 Jun;220:1-13
pubmed: 32299776
Am J Kidney Dis. 2016 Jul;68(1):84-93
pubmed: 27012908
Cell. 2020 Sep 17;182(6):1419-1440.e23
pubmed: 32810438
Cell. 2020 Nov 12;183(4):982-995.e14
pubmed: 32991843
J Infect Dis. 1999 Feb;179(2):508-12
pubmed: 9878040
Am J Respir Crit Care Med. 2020 Nov 1;202(9):1304-1308
pubmed: 32897730
Front Immunol. 2019 Oct 18;10:2458
pubmed: 31681331
Sci Rep. 2021 Jan 15;11(1):1580
pubmed: 33452298
J Clin Invest. 2012 Jan;122(1):327-36
pubmed: 22156198
J Pediatric Infect Dis Soc. 2021 Apr 3;10(3):227-229
pubmed: 32945863
J Clin Invest. 2020 Nov 2;130(11):5942-5950
pubmed: 32701511
Heart Vessels. 2020 Oct;35(10):1463-1472
pubmed: 32449049
EClinicalMedicine. 2020 Sep;26:100527
pubmed: 32923992
J Inflamm Res. 2014 May 29;7:69-87
pubmed: 24971027
Immunobiology. 2016 Jun;221(6):747-51
pubmed: 25956457
N Engl J Med. 1991 Jun 6;324(23):1633-9
pubmed: 1709446
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
J Chin Med Assoc. 2013 Aug;76(8):438-45
pubmed: 23769880
Science. 2007 Aug 3;317(5838):666-70
pubmed: 17673663
J Immunol. 1998 Sep 1;161(5):2636-41
pubmed: 9725266
Clin Nutr. 2021 May;40(5):3436-3447
pubmed: 33309415
J Pediatr. 1997 Mar;130(3):388-93
pubmed: 9063413
Front Immunol. 2021 Mar 08;12:648546
pubmed: 33763085
Cell Rep. 2020 Jul 21;32(3):107923
pubmed: 32697987