Details

Autor(en) / Beteiligte

• Yonker, Lael M
• Gilboa, Tal
• Ogata, Alana F
• Senussi, Yasmeen
• Lazarovits, Roey
• Boribong, Brittany P
• Bartsch, Yannic C
• Loiselle, Maggie
• Rivas, Magali Noval
• Porritt, Rebecca A
• Lima, Rosiane
• Davis, Jameson P
• Farkas, Eva J
• Burns, Madeleine D
• Young, Nicola
• Mahajan, Vinay S
• Hajizadeh, Soroush
• Lopez, Xcanda I Herrera
• Kreuzer, Johannes
• Morris, Robert
• Martinez, Enid E
• Han, Isaac
• Griswold, Jr, Kettner
• Barry, Nicholas C
• Thompson, David B
• Church, George
• Edlow, Andrea G
• Haas, Wilhelm
• Pillai, Shiv
• Arditi, Moshe
• Alter, Galit
• Walt, David R
• Fasano, Alessio

Titel

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier

Ist Teil von

• The Journal of clinical investigation, 2021-07, Vol.131 (14), p.1-12

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2021

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.