A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis

被引：44

作者：

de Cevins, Camille ^{[1
,2
]}

Luka, Marine ^{[1
,3
]}

Smith, Nikaia ^{[4
]}

Meynier, Sonia ^{[5
]}

Magerus, Aude ^{[5
]}

Carbone, Francesco ^{[1
,3
]}

Garcia-Paredes, Victor ^{[1
,3
]}

Barnabei, Laura ^{[5
]}

Batignes, Maxime ^{[1
]}

Boulle, Alexandre ^{[1
]}

Stolzenberg, Marie-Claude ^{[5
]}

Perot, Brieuc P. ^{[1
]}

Charbit, Bruno ^{[6
]}

Fali, Tinhinane ^{[1
]}

Pirabakaran, Vithura ^{[5
]}

Sorin, Boris ^{[5
]}

Riller, Quentin ^{[5
]}

Abdessalem, Ghaith ^{[1
]}

Beretta, Maxime ^{[7
,8
]}

Grzelak, Ludivine ^{[9
]}

Goncalves, Pedro ^{[10
,11
]}

Di Santo, James P. ^{[10
,11
]}

Mouquet, Hugo ^{[7
,8
]}

Schwartz, Olivier ^{[9
]}

Zarhrate, Mohammed ^{[12
,13
]}

Parisot, Melanie ^{[12
,13
]}

Bole-Feysot, Christine ^{[12
,13
]}

Masson, Cecile ^{[14
]}

Cagnard, Nicolas ^{[14
]}

Corneau, Aurelien ^{[15
]}

Brunaud, Camille ^{[5
]}

Zhang, Shen-Ying ^{[16
,17
]}

Casanova, Jean-Laurent ^{[16
,17
,18
]}

Bader-Meunier, Brigitte ^{[18
]}

Haroche, Julien ^{[19
]}

Melki, Isabelle ^{[18
,20
]}

Lorrot, Mathie ^{[21
]}

Oualha, Mehdi ^{[22
]}

Moulin, Florence ^{[22
]}

Bonnet, Damien ^{[23
]}

Belhadjer, Zahra ^{[23
]}

Leruez, Marianne ^{[24
]}

Allali, Slimane ^{[25
]}

Gras-Leguen, Christele ^{[26
]}

de Pontual, Loic ^{[27
]}

Fischer, Alain ^{[18
,28
,29
]}

Duffy, Darragh ^{[4
,6
]}

Rieux-Laucat, Frederic ^{[5
]}

Toubiana, Julie ^{[25
,30
]}

Menager, Mickael M. ^{[1
,3
]}

机构：

[1] Univ Paris, Lab Inflammatory Responses & Transcript Networks, Atip Avenir Team, INSERM UMR 1163, F-75015 Paris, France

[2] Sanofi R&D, Translat Sci, Mol Biol & Gen, Chilly Mazarin, France

[3] INSERM, UMR 1163, Imagine Inst, Labtech Single Cell Imagine, F-75015 Paris, France

[4] Inst Pasteur, Dept Immunol, Translat Immunol Lab, F-75015 Paris, France

[5] Univ Paris, Imagine Inst Lab Immunogenet Pediat Autoimmune Di, INSERM, UMR 1163, F-75015 Paris, France

[6] Inst Pasteur, CRT, Cytometry & Biomarkers UTechS, F-75015 Paris, France

[7] Inst Pasteur, Dept Immunol, Humoral Immunol Lab, F-75015 Paris, France

[8] INSERM U1222, Inst Pasteur, F-75015 Paris, France

[9] Inst Pasteur, Dept Virol, Virus & Immun Unit, F-75015 Paris, France

[10] Inst Pasteur, INSERM U1223, F-75015 Paris, France

[11] Inst Pasteur, Dept Immunol, Innate Immun Unit, F-75015 Paris, France

[12] Paris Cite Univ, Paris Descartes Sorbonne, CNRS UMS3633,INSERM U1163, Gen Core Facil,Inst Imagine Struct Fed Rech Necke, Paris, France

[13] Paris Cite Univ, Paris Descartes Sorbonne, CNRS UMS3633,INSERM US24, Gen Core Facil,Inst Imagine Struct Fed Rech Necke, Paris, France

[14] Univ Paris, Imagine Inst, INSERM UMR1163, Bioinformat Platform Struct Fed Rech Necker, Paris, France

[15] Sorbonne Univ, UMS037, PASS, Plateforme Cytometrie Pitie Salpetriere CyPS, F-75013 Paris, France

[16] Univ Paris, Imagine Inst, Lab Human Genet Infect Dis, Necker Branch,INSERM, F-75015 Paris, France

[17] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA

[18] Hop Necker Enfants Malad, Assistance Publ Hop Paris AP HP, Autoimmune & Syst Dis Children RAISE, Dept Paediat Immunohaematol & Rheumatol,Reference, Paris, France

[19] Sorbonne Univ, Pitie Salpetriere Univ Hosp, AP HP, Dept Immunol & Infect Dis CIMI Paris, F-75013 Paris, France

[20] Univ Paris, Robert Debre Univ Hosp, AP HP, Dept Pediat, Paris, France

[21] Armand Trousseau Univ Hosp, Dept Pediat, AP HP, F-75012 Paris, France

[22] Univ Paris, Necker Enfants Malad Univ Hosp, AP HP, Pediatr Intens Care Unit, F-75015 Paris, France

[23] M3C Necker Enfants Malad, AP HP, Paris, France

[24] Univ Paris, AP HP, Necker Enfants Malad Univ Hosp, Virol Lab, F-75015 Paris, France

[25] Univ Paris, Necker Enfants Malad Univ Hosp, Assistance Publ Hop Paris AP HP, Dept Gen Paediat & Paediat Infect Dis, F-75015 Paris, France

[26] Nantes Univ Hosp, CIC 1413, INSERM, Pediatr Dept, F-44000 Nantes, France

[27] Univ Paris 13, Jean Verdier Hosp, Assistance Publ Hop Paris, Dept Pediat, Bondy, France

[28] Univ Paris, Imagine Inst, INSERM, UMR 1163, F-75015 Paris, France

[29] Coll France, Paris, France

[30] Inst Pasteur, Biodivers & Epidemiol Bacterial Pathogens, Paris, France

来源：

MED | 2021年 / 2卷 / 09期

关键词：

TUMOR-NECROSIS-FACTOR; INTRAVENOUS IMMUNOGLOBULIN; DENDRITIC CELLS; KAWASAKI-DISEASE; DIAGNOSIS; CORONAVIRUS; COVID-19;

D O I：

10.1016/j.medj.2021.08.002

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. Methods: To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. Findings: The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor kappa B (NF-kappa B) activity and tumor necrosis factor alpha (TNF-alpha) signaling and associated with decreased gene expression of NF-kappa B inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1 alpha and Vascular endothelial growth factor (VEGF) signaling. Conclusions: These results provide potential for a better understanding of disease pathophysiology.

引用

页码：1072 / +

页数：29

共 82 条

[11] The Mystery of MIS-C Post-SARS-CoV-2 Infection [J].