Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination-Induced Myocarditis.
Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination-Induced Myocarditis.
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DOI：
10.1001/jamanetworkopen.2023.14291
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发表时间：
2023-05-01
影响因子：
13.8
通讯作者：
Levin, Michael
中科院分区：
文献类型：
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作者：
Patel, Harsita;Sintou, Amalia;Chowdhury, Rasheda A.;Rothery, Stephen;Iacob, Alma Octavia;Prasad, Sanjay;Rainer, Peter P.;Martinon-Torres, Federico;Sancho-Shimizu, Vanessa;Shimizu, Chisato;Dummer, Kirsten;Tremoulet, Adriana H.;Burns, Jane C.;Sattler, Susanne;Levin, Michael
靶向心脏的自身抗体是否在儿童sars - cov -2相关多系统炎症综合征（MIS-C）或COVID-19 mRNA疫苗的心脏并发症中发挥作用？这项诊断研究包括20名患有misc或COVID - 19疫苗诱导的心肌炎的儿童和21名成人和儿童对照，未发现misc或疫苗诱导的心肌炎患者血清中存在结合供体心脏组织的自身抗体的证据。这些结果表明，抗心脏自身抗体不太可能在misc或COVID-19疫苗诱导的心肌炎的心脏病理中发挥作用。本诊断研究评估了多系统炎症综合征和COVID-19疫苗诱导的心肌炎儿童中抗心脏自身抗体的存在。心功能障碍和心肌炎已成为儿童多系统炎症综合征（MIS-C）和SARS-CoV-2疫苗的严重并发症。了解自身抗体在这些情况下的作用对于指导儿童misc的管理和疫苗接种策略至关重要。目的探讨misc或COVID-19疫苗诱导的心肌炎中抗心脏自身抗体的存在。该诊断研究包括急性misc或急性疫苗性心肌炎的儿童、患有心肌炎或炎症性心肌病的成人、COVID-19大流行前的健康儿童和健康的COVID-19疫苗接种成人。从2021年1月开始，参与者被招募到美国、英国和奥地利进行研究。免疫球蛋白G （IgG）、IgM和IgA抗心脏自身抗体通过免疫荧光染色从2个供体左心室心肌组织与患者和对照组血清处理。二抗是异硫氰酸荧光素偶联的抗人IgG、IgM和IgA。成像检测特异性IgG、IgM、IgA沉积，测定异硫氰酸荧光素荧光强度。数据分析截止到2023年3月10日。IgG， IgM和IgA抗体与心脏组织结合。通过队列研究，共有10名患有misc的儿童（年龄中位数为10[13-14]岁，6名男性），10名患有疫苗心肌炎的儿童（年龄中位数为15[14-16]岁，10名男性），8名患有心肌炎或炎症性心肌病的成年人（年龄中位数为55[46-63]岁，6名男性），10名健康儿童对照（年龄中位数为8[13-14]岁，5名男性），10名健康接种疫苗的成年人（年龄均大于21岁，5名男性）。在使用小儿misc或疫苗性心肌炎患者血清处理的人心脏组织中，未观察到高于背景的抗体结合。8例成人心肌炎或心肌病患者中有1例IgG染色阳性，荧光强度升高（中位[IQR]强度为116060 [10 223- 11858]AU）。与对照组相比，所有其他患者队列中IgG (misc, 6033 [5834-6756] AU，疫苗心肌炎，6392 [5710-6836]AU，成人心肌炎或炎症性心肌病，5688 [5277-5990]AU，健康儿童对照组，6235 [5924-6708]AU，健康接种成人，7000 [6423-7739]AU), IgM (misc, 3354 [3110-4043] AU，疫苗心肌炎，3843 [3288-4748]AU，健康儿童对照组，3436 [3313-4237]AU；健康接种成人，3543 [2997-4607]AU)和IgA （misc, 3559 [2788-4466] AU；疫苗心肌炎，4389 [2393-4780]AU；健康儿童对照，3436 [2425-4077]AU；健康接种成人，4561 [3164-6309]AU）。本病因诊断研究未发现来自MIS-C和COVID-19疫苗心肌炎血清的抗体结合心脏组织的证据，提示这两种情况下的心脏病理不太可能由直接的抗心脏抗体介导机制驱动。
Do autoantibodies targeting the heart play a role in the cardiac complications of SARS-CoV-2–associated multisystem inflammatory syndrome in children (MIS-C) or COVID-19 mRNA vaccination? This diagnostic study including 20 children with MIS-C or COVID 19 vaccine–induced myocarditis and 21 adult and pediatric controls found no evidence of autoantibodies in serum of patients with MIS-C or vaccine-induced myocarditis binding donor cardiac tissue. These results suggest that anticardiac autoantibodies are unlikely to play a role in the cardiac pathology seen in MIS-C or COVID-19 vaccine–induced myocarditis. This diagnostic study assesses the presence of anticardiac autoantibodies in children with multisystem inflammatory syndrome and COVID-19 vaccine–induced myocarditis. 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. To investigate the presence of anticardiac autoantibodies in MIS-C or COVID-19 vaccine-induced myocarditis. 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. IgG, IgM and IgA antibody binding to cardiac tissue. 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). 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.
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影响因子：
105.7
作者：
Pillay, Jennifer;Gaudet, Lindsay;Wingert, Aireen;Bialy, Liza;Mackie, Andrew S.;Paterson, D. Ian;Hartling, Lisa
通讯作者：
Hartling, Lisa
影响因子：
15.9
作者：
Yonker, Lael M.;Gilboa, Tal;Fasano, Alessio
通讯作者：
Fasano, Alessio
影响因子：
64.5
作者：
Gruber, Conor N.;Patel, Roosheel S.;Bogunovic, Dusan
通讯作者：
Bogunovic, Dusan
DOI：
10.1093/cid/ciac160
发表时间：
2022-10-12
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Sigal GB;Novak T;Mathew A;Chou J;Zhang Y;Manjula N;Bathala P;Joe J;Padmanabhan N;Romero D;Allegri-Machado G;Joerger J;Loftis LL;Schwartz SP;Walker TC;Fitzgerald JC;Tarquinio KM;Zinter MS;Schuster JE;Halasa NB;Cullimore ML;Maddux AB;Staat MA;Irby K;Flori HR;Coates BM;Crandall H;Gertz SJ;Randolph AG;Pollock NR;Overcoming COVID-19 Investigators
通讯作者：
Overcoming COVID-19 Investigators
DOI：
10.1038/s41569-021-00662-w
发表时间：
2022-03
期刊：
Nature reviews. Cardiology
影响因子：
--
作者：
Heymans S;Cooper LT
通讯作者：
Cooper LT