Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis
-
Published:2023-05-18
Issue:5
Volume:6
Page:e2314291
-
ISSN:2574-3805
-
Container-title:JAMA Network Open
-
language:en
-
Short-container-title:JAMA Netw Open
Author:
Patel Harsita1, Sintou Amalia2, Chowdhury Rasheda A.2, Rothery Stephen2, Iacob Alma Octavia23, Prasad Sanjay3, Rainer Peter P.45, Martinón-Torres Federico678, Sancho-Shimizu Vanessa1910, Shimizu Chisato1112, Dummer Kirsten1112, Tremoulet Adriana H.1112, Burns Jane C.1112, Sattler Susanne24, Levin Michael1, Cunnington Aubrey13, Herberg Jethro13, Kaforou Myrsini13, Wright Victoria J.13, Bellos Evangelos13, Broderick Claire13, Channon-Wells Samuel13, Cooray Samantha13, De Tisham13, D’Souza Giselle13, Estramiana Elorrieta Leire13, Estrada-Rivadeneyra Diego13, Galassini Rachel13, Habgood-Coote Dominic13, Hamilton Shea13, Jackson Heather13, Kavanagh James13, Keren Ilana13, Moradi Marjaneh Mahdi13, Menikou Stephanie13, Nichols Samuel13, Nijman Ruud13, Pennisi Ivana13, Powell Oliver13, Reid Ruth13, Shah Priyen13, Vito Ortensia13, Whittaker Elizabeth13, Wilson Clare13, Womersley Rebecca13, Abdulla Amina13, Darnell Sarah13, Mustafa Sobia13, Georgiou Pantelis13, Manzano Jesus-Rodriguez13, Moser Nicolas13, Carter Michael13, Tibby Shane13, Cohen Jonathan13, Davis Francesca13, Kenny Julia13, Wellman Paul13, White Marie13, Fish Matthew13, Jennings Aislinn13, Shankar-Hari Manu13, Fidler Katy13, Agranoff Dan13, Richmond Vivien13, Seal Mathhew13, Faust Saul13, Owen Dan13, Ensom Ruth13, McKay Sarah13, Shaji Mariya13, Schranz Rachel13, Rughnani Prita13, Anpananthar Amutha13, Liebeschuetz Susan13, Riddell Anna13, Divakaran Divya13, Han Louise13, Khalid Nosheen13, Malcolm Ivone Lancoma13, Schofield Jessica13, Simagan Teresa13, Peters Mark13, Bamford Alasdair13, O’Neill Lauran13, Pathan Nazima13, Daubney Esther13, White Deborah13, Heightman Melissa13, Eisen Sarah13, Segal Terry13, Wellings Lucy13, B Drysdale Simon13, Branch Nicole13, Hamzah Lisa13, Jarman Heather13, Nyirenda Maggie13, Capozzi Lisa13, Gardiner Emma13, Moots Robert13, Nasher Magda13, Hanson Anita13, Linforth Michelle13, O’Riordan Sean13, Ellis Donna13, Deep Akash13, Caro Ivan13, Shackley Fiona13, Bellini Arianna13, Gormley Stuart13, Neshat Samira13, Scholefield Barnaby13, Robbins Ceri13, Winmill Helen13, Paulus Stéphane C13, Pollard Andrew J13, Anthony Mark13, Hopton Sarah13, Miller Danielle13, Oliver Zoe13, Beer Sally13, Ward Bryony13, Shrestha Shrijana13, Gurung Meeru13, Amatya Puja13, Pokhrel Bhishma13, Bijukchhe Sanjeev Man13, Gautam Madhav Chandra13, Kelly Sarah13, O’Reilly Peter13, Shrestha Sonu13, Martinón-Torres Federico13, Salas Antonio13, González Fernando Álvez13, Gómez Sonia Ares13, Bello Xabier13, García Mirian Ben13, Viña Fernando Caamaño13, Carnota Sandra13, Curras-Tuala María José13, Urbieta Ana Dacosta13, Suárez Carlos Durán13, Vidal Isabel Ferreiros13, Vicente Luisa García13, Gómez-Carballa Alberto13, Rial Jose Gómez13, Iglesias Pilar Leboráns13, Mallah Narmeen13, Martinón-Torres Nazareth13, Martinón José María13, Sánchez Belén Mosquera Pérez13, Pardo-Seco Jacobo13, Pischedda Sara13, Vázquez Sara Rey13, Calle Irene Rivero13, Rodríguez-Tenreiro Carmen13, Redondo-Collazo Lorenzo13, Fernández Sonia Serén13, Iglesias Marisol Vilas13, Carrol Enitan D13, Cocklin Elizabeth13, Beckley Rebecca13, Bracken Abbey13, Evans Ceri13, Khanijau Aakash13, Lenihan Rebecca13, Lewis-Burke Nadia13, Newall Karen13, Romaine Sam13, Whitbread Jennifer13, Tsolia Maria13, Eleftheriou Irini13, Spyridis Nikos13, Tambouratzi Maria13, Maritsi Despoina13, Marmarinos Antonios13, Xagorari Marietta13, Panagiota Lourida13, Aggelos Pefanis13, Karolina Akinosoglou13, Charalambos Gogos13, Markos Maragos13, Michalis Voulgarelis13, Ioanna Stergiou13, Emonts Marieke13, Lim Emma13, Isaacs John13, Bell Kathryn13, Crulley Stephen13, Fabian Daniel13, Thomson Evelyn13, Wallia Diane13, Miller Caroline13, Bell Ashley13, van der Velden Fabian J S13, Shenton Geoff13, Price Ashley13, Treloar Owen13, Thomas Daisy13, Rojo Pablo13, Epalza Cristina13, Villaverde Serena13, Márquez Sonia13, Gijón Manuel13, Machín Fátima13, Cabello Laura13, Hernández Irene13, Gutiérrez Lourdes13, Manzanares Ángela13, Kuijpers Taco W13, van de Kuip Martijn13, van Furth Marceline13, van den Berg Merlijn13, Biesbroek Giske13, Verkuil Floris13, van der Zee Carlijn13, Pajkrt Dasja13, van Hensbroek Michael Boele13, Schonenberg Dieneke13, Gruppen Mariken13, Nagelkerke Sietse13, Jansen MachielH13, Goetschalckx Ines13, Romani Lorenza13, De Luca Maia13, Chiurchiù Sara13, Tripiciano Costanza13, Mercadante Stefania13, Vermont Clementien L13, Moll Henriëtte A13, Borensztajn Dorine M13, Hagedoorn Nienke N13, Tan Chantal13, Zachariasse Joany13, Dik W13, Shen Ching-Fen13, Zavadska Dace13, Laivacuma Sniedze13, Rudzate Aleksandra13, Stoldere Diana13, Barzdina Arta13, Barzdina Elza13, Madelane Monta13, Gravele Dagne13, Svilz Dace13, Basmaci Romain13, Lachaume Noémie13, Bories Pauline13, Tkhayat RajaBen13, Chériaux Laura13, Davoust Juraté13, Ong Kim-Thanh13, Cotillon Marie13, de Groc Thibault13, Le Sébastien13, Vergnault Nathalie13, Sée Hélène13, Cohen Laure13, de Tugny Alice13, Danekova Nevena13, Mommert-Tripon Marine13, Brengel-Pesce Karen13, Pokorn Marko13, Kolnik Mojca13, Avčin Tadej13, Avramoska Tanja13, Bahovec Natalija13, Bogovič Petra13, Kitanovski Lidija13, Nahtigal Mirijam13, Papst Lea13, Plankar Srovin Tina13, Strle Franc13, Vincek Katarina13, van der Flier Michiel13, Tissing Wim J E13, Wösten-van Asperen Roelie M13, Vastert Sebastiaan J13, Vijlbrief Daniel C13, Bont Louis J13, Beudeker Coco R13, Agyeman Philipp13, Schlapbach Luregn13, Aebi Christoph13, Usman Mariama13, Schlüchter Stefanie13, Wyss Verena13, Schöbi Nina13, Zimmermann Elisa13, Meier Marion13, Weber Kathrin13, Fink Colin13, Voice Marie13, Calvo-Bado Leo13, Steele Michael13, Holden Jennifer13, Taylor Andrew13, Calvez Ronan13, Davies Catherine13, Evans Benjamin13, Stevens Jake13, Matthews Peter13, Billing Kyle13, Zenz Werner13, Binder Alexander13, Kohlmaier Benno13, Kohlfürst Daniela S13, Schweintzger Nina A13, Zurl Christoph13, Hösele Susanne13, Leitner Manuel13, Pölz Lena13, Rusu Alexandra13, Rajic Glorija13, Stoiser Bianca13, Strempfl Martina13, Sagmeister Manfred G13, Bauchinger Sebastian13, Benesch Martin13, Ceolotto Astrid13, Eber Ernst13, Gallistl Siegfried13, Haidl Harald13, Hauer Almuthe13, Hude Christa13, Kapper Andreas13, Keldorfer Markus13, Löffler Sabine13, Niedrist Tobias13, Pilch Heidemarie13, Pfleger Andreas13, Pfurtscheller Klaus13, Rödl Siegfried13, Skrabl-Baumgartner Andrea13, Strenger Volker13, Wallner Elmar13, Tauchert Maike K13, Yeung Shunmay13, Dewez Manuel13, Bath David13, Fitchett Elizabeth13, Cresswell Fiona13, Usuf Effua13, Bojang Kalifa13, Roca Anna13, Sarr Isatou13, Saidykhan Momodou13, Ndure Ebrahim13, von Both Ulrich13, Kolberg Laura13, Schmied Patricia13, Mavridi Ioanna13, Alba-Alejandre Irene13, Haas Nikolaus13, Maier Esther13, Juranek Sabrina13, Feuchtinger Tobias13, Danhauser Katharina13, Griese Matthias13, Kappler Matthias13, Lurz Eberhard13, Schroepf Sebastian13, Hoffmann Florian13, Reiter Karl13, Schoen Carola13, Schlapbach Luregn J13, Giannoni Eric13, Stocker Martin13, Posfay-Barbe Klara M13, Heininger Ulrich13, Bernhard-Stirnemann Sara13, Niederer-Loher Anita13, Kahlert Christian13, Natalucci Giancarlo13, Relly Christa13, Berger Christoph13, Riedel Thomas13,
Affiliation:
1. Department of Infectious Disease, Section of Paediatric Infectious Disease, Imperial College London, United Kingdom 2. National Heart & Lung Institute, Faculty of Medicine, Imperial College London, United Kingdom 3. Royal Brompton & Harefield hospitals, Guy’s and St Thomas’ National Health Service Foundation Trust, United Kingdom 4. Department of Cardiology, Medical University of Graz, Graz, Austria 5. BioTechMed Graz, Graz, Austria 6. Genetics, Vaccines and Infections Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain 7. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain 8. Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain 9. Department of Infectious Disease, Section of Virology, Imperial College London, London, United Kingdom 10. Centre for Paediatrics and Child Health, Faculty of Medicine, Imperial College London, London, United Kingdom 11. Department of Pediatrics, School of Medicine, University of California, San Diego, San Diego 12. Rady Children’s Hospital, San Diego, California 13. for the DIAMONDS consortium
Abstract
ImportanceCardiac dysfunction and myocarditis have emerged as serious complications of multisystem inflammatory syndrome in children (MIS-C) and vaccines against SARS-CoV-2. Understanding the role of autoantibodies in these conditions is essential for guiding MIS-C management and vaccination strategies in children.ObjectiveTo investigate the presence of anticardiac autoantibodies in MIS-C or COVID-19 vaccine-induced myocarditis.Design, Setting, and ParticipantsThis diagnostic study included children with acute MIS-C or acute vaccine myocarditis, adults with myocarditis or inflammatory cardiomyopathy, healthy children prior to the COVID-19 pandemic, and healthy COVID-19 vaccinated adults. Participants were recruited into research studies in the US, United Kingdom, and Austria starting January 2021. Immunoglobulin G (IgG), IgM, and IgA anticardiac autoantibodies were identified with immunofluorescence staining of left ventricular myocardial tissue from 2 human donors treated with sera from patients and controls. Secondary antibodies were fluorescein isothiocyanate–conjugated antihuman IgG, IgM, and IgA. Images were taken for detection of specific IgG, IgM, and IgA deposits and measurement of fluorescein isothiocyanate fluorescence intensity. Data were analyzed through March 10, 2023.Main Outcomes and MeasuresIgG, IgM and IgA antibody binding to cardiac tissue.ResultsBy cohort, there were a total of 10 children with MIS-C (median [IQR] age, 10 [13-14] years; 6 male), 10 with vaccine myocarditis (median age, 15 [14-16] years; 10 male), 8 adults with myocarditis or inflammatory cardiomyopathy (median age, 55 [46-63] years; 6 male), 10 healthy pediatric controls (median age, 8 [13-14] years; 5 male), and 10 healthy vaccinated adults (all older than 21 years, 5 male). No antibody binding above background was observed in human cardiac tissue treated with sera from pediatric patients with MIS-C or vaccine myocarditis. One of the 8 adult patients with myocarditis or cardiomyopathy had positive IgG staining with raised fluorescence intensity (median [IQR] intensity, 11 060 [10 223-11 858] AU). There were no significant differences in median fluorescence intensity in all other patient cohorts compared with controls for IgG (MIS-C, 6033 [5834-6756] AU; vaccine myocarditis, 6392 [5710-6836] AU; adult myocarditis or inflammatory cardiomyopathy, 5688 [5277-5990] AU; healthy pediatric controls, 6235 [5924-6708] AU; healthy vaccinated adults, 7000 [6423-7739] AU), IgM (MIS-C, 3354 [3110-4043] AU; vaccine myocarditis, 3843 [3288-4748] AU; healthy pediatric controls, 3436 [3313-4237] AU; healthy vaccinated adults, 3543 [2997-4607] AU) and IgA (MIS-C, 3559 [2788-4466] AU; vaccine myocarditis, 4389 [2393-4780] AU; healthy pediatric controls, 3436 [2425-4077] AU; healthy vaccinated adults, 4561 [3164-6309] AU).Conclusions and RelevanceThis etiological diagnostic study found no evidence of antibodies from MIS-C and COVID-19 vaccine myocarditis serum binding cardiac tissue, suggesting that the cardiac pathology in both conditions is unlikely to be driven by direct anticardiac antibody–mediated mechanisms.
Publisher
American Medical Association (AMA)
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|