Zhang Jingdi, Xu Honglin, Li Zhan, Feng Futai, Wang Siyu, Li Yongzhe
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China,.
Autoimmun Rev. 2025 Mar 26;24(4):103755. doi: 10.1016/j.autrev.2025.103755. Epub 2025 Jan 22.
Dilated cardiomyopathy (DCM) is a prevalent myocardial disorder characterized by impaired cardiac function affecting either the left ventricle or both ventricles. Accumulating evidence suggests that autoimmunity represents a key mechanism implicated in its pathogenesis, as several abundant autoantibodies have been identified in patients with the condition. However, the prevalence of these antibodies (Abs) in patients with DCM compared to that in both healthy controls (HCs) and those with ischemic cardiomyopathy (ICM), as well as their potential association with DCM, remains unclear. This study aimed to elucidate the prevalence of certain autoantibodies in patients with DCM compared to that in HCs and patients with ICM, as well as to evaluate their correlation with clinical characteristics and outcomes.
A comprehensive literature search of the PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus was conducted up to March 26, 2024, and any article that fulfilled our inclusion criteria was reviewed. A meta-analysis was then conducted, using both random- and fixed-effects models.
A total of 38 studies met the inclusion criteria and were pulled for this analysis. Significantly higher prevalence rates of autoantibodies targeting the anti-β1 adrenergic receptor (β1-AR; odds ratio [OR] = 4.96, p = 0.000), M2 muscarinic receptor (M2-R; OR = 4.07, p = 0.000), adenine nucleotide translocator (ANT; OR = 21.18, p = 0.001) and myosin (OR = 12.26, p = 0.000) were observed in patients with DCM compared to HCs. Moreover, patients with DCM exhibited a significantly higher frequency of positive ANT Abs (OR = 34.52, p = 0.005) compared to those with ICM. Regarding clinical characteristics and outcomes, seropositivity for β1-AR Abs was found to be significantly correlated with New York Heart Association (NYHA) classification (standardized mean difference [SMD] = 0.78, p = 0.006), left ventricular ejection fraction (LVEF) (SMD = -1.38, p = 0.001), and heart rate (HR) (SMD = 1.505, p = 0.022). Seropositivity for anti‑calcium channel Abs was significantly associated with sudden cardiac death (SCD; OR = 3.17, p = 0.000) and all-cause mortality (OR = 2.06, p = 0.008), while anti-troponin I (TnI) Abs were associated with atrial fibrillation (OR = 0.21, p = 0.042). In terms of Ab prevalence rates, significant heterogeneity in the frequency of anti-β1-AR Abs between studies investigating DCM and ICM may be partially explained by the detection methods used and the mean ages of the patients. Meta-regression analysis suggested that the patients' ages may partially explain the observed heterogeneity between studies regarding β1-AR Ab seropositivity and HR. However, the heterogeneity observed in the studies comparing the prevalences of Abs in patients with DCM vs HCs and ICM, as well as their associated clinical characteristics, could not be explained by subgroup analyses or demographic factors such as age and sex-nor by cardiac function.
Patients with DCM are more likely to have elevated levels of anti- β1-AR, M2-R, ANT and myosin autoantibodies compared to HCs, as well as higher levels of ANT Abs compared to patients with ICM. Anti-β1-AR, calcium channel, and TnI Abs may play an essential role in DCM severity and poor prognosis. This study represents the first comprehensive meta-analysis regarding autoantibody prevalence and DCM and may thus potentially guide the clinical management of such patients. However, further research is warranted to evaluate the accuracy of this presumed role of autoantibodies in DCM, owing to the small number of the studies included and their high degree of heterogeneity.
扩张型心肌病（DCM）是一种常见的心肌疾病，其特征是心脏功能受损，影响左心室或双心室。越来越多的证据表明，自身免疫是其发病机制中的一个关键机制，因为在患有该疾病的患者中已鉴定出几种丰富的自身抗体。然而，与健康对照（HCs）和缺血性心肌病（ICM）患者相比，这些抗体（Abs）在DCM患者中的患病率，以及它们与DCM的潜在关联仍不清楚。本研究旨在阐明与HCs和ICM患者相比，DCM患者中某些自身抗体的患病率，并评估它们与临床特征和结局的相关性。
截至2024年3月26日，对PubMed、Web of Science、EMBASE、Cochrane图书馆和Scopus进行了全面的文献检索，并对符合我们纳入标准的任何文章进行了审查。然后使用随机效应模型和固定效应模型进行荟萃分析。
共有38项研究符合纳入标准并被纳入本分析。与HCs相比，DCM患者中靶向抗β1肾上腺素能受体（β1-AR；优势比[OR]=4.96，p=0.000）、M2毒蕈碱受体（M2-R；OR=4.07，p=0.000）、腺嘌呤核苷酸转位酶（ANT；OR=21.18，p=0.001）和肌球蛋白（OR=12.26，p=0.000）的自身抗体患病率显著更高。此外，与ICM患者相比，DCM患者中ANT Abs阳性频率显著更高（OR=34.52，p=0.005）。关于临床特征和结局，发现β1-AR Abs血清阳性与纽约心脏协会（NYHA）分级（标准化均数差[SMD]=0.78，p=0.006）、左心室射血分数（LVEF）（SMD=-1.38，p=0.001）和心率（HR）（SMD=1.505，p=0.022）显著相关。抗钙通道Abs血清阳性与心源性猝死（SCD；OR=3.17，p=0.000）和全因死亡率（OR=2.06，p=0.008）显著相关，而抗肌钙蛋白I（TnI）Abs与心房颤动（OR=0.21，p=0.042）相关。在抗体患病率方面，研究DCM和ICM的研究之间抗β1-AR Abs频率的显著异质性可能部分由所使用的检测方法和患者的平均年龄解释。荟萃回归分析表明，患者年龄可能部分解释了研究之间关于β1-AR Ab血清阳性和HR的观察到的异质性。然而，在比较DCM与HCs和ICM患者中抗体患病率及其相关临床特征的研究中观察到的异质性，不能通过亚组分析或年龄和性别等人口统计学因素或心功能来解释。
与HCs相比，DCM患者更有可能具有升高水平的抗β1-AR、M2-R、ANT和肌球蛋白自身抗体，并且与ICM患者相比，ANT Abs水平更高。抗β1-AR、钙通道和TnI Abs可能在DCM严重程度和不良预后中起重要作用。本研究代表了关于自身抗体患病率与DCM的首次全面荟萃分析，因此可能潜在地指导此类患者的临床管理。然而，由于纳入的研究数量较少且异质性程度较高，因此有必要进行进一步研究以评估自身抗体在DCM中这种假定作用的准确性。
