Proteomics

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Multisystem inflammatory syndrome in children (MIS-C) serum proteomics


ABSTRACT: While fewer cases of severe Coronavirus Disease 2019 (COVID-19) are reported globally in children, a small proportion of SARS-CoV-2 infected children develop a novel pediatric febrile entity called multisystem inflammatory syndrome in children (MIS-C) that develops 2 to 5 weeks after initial SARS-CoV-2 exposure. MIS-C primarily effects male children and children of Hispanic or black descent. MIS-C manifests as a severe and uncontrolled inflammatory response with multiorgan involvement. A hyperinflammatory state is evidenced by clinical makers of inflammation including high levels of C-reactive protein (CRP), ferritin, and D-dimers, and an increased expression of pro-inflammatory cytokines. Children often present with persistent fever, severe gastrointestinal symptoms, cardiovascular manifestations, respiratory symptoms and neurological symptoms6-11,13. Cardiovascular manifestations include hypotension, shock, cardiac dysfunction, myocarditis and pericardial effusion. In the united states, admission to the intensive care unit occurs in approximately 58% of cases. To understand disease pathogenesis of MIS-C and proteins associated with the severe form of disease we performed proteomics analysis of serum or plasma samples. We collected serum from healthy children (SARS-CoV-2 negative, n=20), mild MIS-C (non-ICU, n=5) and severe MIS-C (ICU, n = 20) patients. MIS-C definition and diagnosis was performed according to CDC guidelines. Healthy adult serum (n = 4) was also used for reference ranges quality control and we obtained plasma samples from Kawasaki Disease (KD; n=7) patients that were recruited before the Coronavirus Disease 2019 (COVID-19) pandemic.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Aleksandra Binek  

LAB HEAD: Jennifer Van Eyk

PROVIDER: PXD025462 | Pride | 2021-09-29

REPOSITORIES: Pride

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Publications

The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children.

Porritt Rebecca A RA   Binek Aleksandra A   Paschold Lisa L   Rivas Magali Noval MN   McArdle Angela A   Yonker Lael M LM   Alter Galit G   Chandnani Harsha K HK   Lopez Merrick M   Fasano Alessio A   Van Eyk Jennifer E JE   Binder Mascha M   Arditi Moshe M  

The Journal of clinical investigation 20211001 20


Multisystem inflammatory syndrome in children (MIS-C) manifests as a severe and uncontrolled inflammatory response with multiorgan involvement, occurring weeks after SARS-CoV-2 infection. Here, we utilized proteomics, RNA sequencing, autoantibody arrays, and B cell receptor (BCR) repertoire analysis to characterize MIS-C immunopathogenesis and identify factors contributing to severe manifestations and intensive care unit admission. Inflammation markers, humoral immune responses, neutrophil activ  ...[more]

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