Simpson Kathleen E, Cunningham Madeleine W, Lee Caroline K, Ward Kent, Tong Alan, Danon Saar, Simon Catherine, Delaney Jeffrey W, Canter Charles E
Washington University School of Medicine in St Louis, St Louis, Missouri.
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
J Card Fail. 2016 Jul;22(7):520-8. doi: 10.1016/j.cardfail.2016.02.009. Epub 2016 Mar 3.
Host autoimmune activity in myocarditis has been proposed to play a role in development of cardiac disease, but evidence of autoimmunity and relationship to outcomes have not been evaluated in pediatric myocarditis.
We performed a multi-institutional study of children with clinical myocarditis. Newly diagnosed patients were followed for up to 12 months and previously diagnosed patients at a single follow-up for serum levels of autoantibodies to human cardiac myosin, beta-adrenergic receptors 1 and 2, muscarinic-2 receptors, and antibody-mediated protein kinase A (PKA) activation in heart cells in culture. Results were compared with those of healthy control children.
Both previously diagnosed patient at follow-up (P = .0061) and newly diagnosed patients at presentation (P = .0127) had elevated cardiac myosin antibodies compared with control subjects. Antibody levels were not associated with recovery status at follow-up in either group. PKA activation was higher at presentation in the newly diagnosed patients who did not recovery normal function (P = .042).
Children with myocarditis have evidence of autoantibodies against human cardiac myosin at diagnosis and follow-up compared with control subjects. Differences in antibody-mediated cell signaling may contribute to differences in patient outcomes, as suggested by elevated antibody-mediated PKA activation in heart cells by the serum from nonrecovered patients.
已有研究提出,宿主在心肌炎中的自身免疫活动在心脏疾病的发展中起作用,但在儿童心肌炎中,自身免疫的证据及其与预后的关系尚未得到评估。
我们对患有临床心肌炎的儿童进行了一项多机构研究。新诊断的患者随访长达12个月,先前诊断的患者在单次随访中检测血清中针对人心脏肌球蛋白、β-肾上腺素能受体1和2、毒蕈碱-2受体的自身抗体水平,以及培养的心脏细胞中抗体介导的蛋白激酶A(PKA)激活情况。将结果与健康对照儿童的结果进行比较。
与对照组相比,先前诊断的患者在随访时(P = 0.0061)和新诊断的患者在就诊时(P = 0.0127)心脏肌球蛋白抗体均升高。两组中抗体水平均与随访时的恢复状态无关。在未恢复正常功能的新诊断患者中,就诊时PKA激活水平较高(P = 0.042)。
与对照组相比,心肌炎患儿在诊断和随访时均有针对人心脏肌球蛋白的自身抗体证据。抗体介导的细胞信号传导差异可能导致患者预后不同,未恢复患者血清使心脏细胞中抗体介导的PKA激活升高表明了这一点。