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Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis
IMPORTANCE: Cardiac 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 strat...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196878/ https://www.ncbi.nlm.nih.gov/pubmed/37200028 http://dx.doi.org/10.1001/jamanetworkopen.2023.14291 |
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author | Patel, Harsita Sintou, Amalia Chowdhury, Rasheda A. Rothery, Stephen Iacob, Alma Octavia Prasad, Sanjay Rainer, Peter P. Martinón-Torres, Federico Sancho-Shimizu, Vanessa Shimizu, Chisato Dummer, Kirsten Tremoulet, Adriana H. Burns, Jane C. Sattler, Susanne Levin, Michael |
author_facet | Patel, Harsita Sintou, Amalia Chowdhury, Rasheda A. Rothery, Stephen Iacob, Alma Octavia Prasad, Sanjay Rainer, Peter P. Martinón-Torres, Federico Sancho-Shimizu, Vanessa Shimizu, Chisato Dummer, Kirsten Tremoulet, Adriana H. Burns, Jane C. Sattler, Susanne Levin, Michael |
author_sort | Patel, Harsita |
collection | PubMed |
description | IMPORTANCE: Cardiac 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. OBJECTIVE: To investigate the presence of anticardiac autoantibodies in MIS-C or COVID-19 vaccine-induced myocarditis. DESIGN, SETTING, AND PARTICIPANTS: This 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 MEASURES: IgG, IgM and IgA antibody binding to cardiac tissue. RESULTS: By 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 RELEVANCE: This 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. |
format | Online Article Text |
id | pubmed-10196878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-101968782023-05-20 Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis Patel, Harsita Sintou, Amalia Chowdhury, Rasheda A. Rothery, Stephen Iacob, Alma Octavia Prasad, Sanjay Rainer, Peter P. Martinón-Torres, Federico Sancho-Shimizu, Vanessa Shimizu, Chisato Dummer, Kirsten Tremoulet, Adriana H. Burns, Jane C. Sattler, Susanne Levin, Michael JAMA Netw Open Original Investigation IMPORTANCE: Cardiac 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. OBJECTIVE: To investigate the presence of anticardiac autoantibodies in MIS-C or COVID-19 vaccine-induced myocarditis. DESIGN, SETTING, AND PARTICIPANTS: This 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 MEASURES: IgG, IgM and IgA antibody binding to cardiac tissue. RESULTS: By 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 RELEVANCE: This 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. American Medical Association 2023-05-18 /pmc/articles/PMC10196878/ /pubmed/37200028 http://dx.doi.org/10.1001/jamanetworkopen.2023.14291 Text en Copyright 2023 Patel H et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License. |
spellingShingle | Original Investigation Patel, Harsita Sintou, Amalia Chowdhury, Rasheda A. Rothery, Stephen Iacob, Alma Octavia Prasad, Sanjay Rainer, Peter P. Martinón-Torres, Federico Sancho-Shimizu, Vanessa Shimizu, Chisato Dummer, Kirsten Tremoulet, Adriana H. Burns, Jane C. Sattler, Susanne Levin, Michael Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis |
title | Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis |
title_full | Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis |
title_fullStr | Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis |
title_full_unstemmed | Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis |
title_short | Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis |
title_sort | evaluation of autoantibody binding to cardiac tissue in multisystem inflammatory syndrome in children and covid-19 vaccination–induced myocarditis |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196878/ https://www.ncbi.nlm.nih.gov/pubmed/37200028 http://dx.doi.org/10.1001/jamanetworkopen.2023.14291 |
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