单独和联合检测抗心肌抗体对病毒性心脏病的诊断价值

发布时间：2018-08-19 08:35

【摘要】：第一部分病毒性心肌炎患者抗钙通道抗体的测定目的：众多研究表明,病毒性心肌炎(VMC)、扩张型心肌病(DCM)均与病毒感染及其后的自身免疫反应有关,故有学者将二者统称为病毒性心脏病(VHD)。既往研究发现,在VHD患者体内存在多种抗心肌自身抗体(AHA),其中国际上较为公认的四种抗心肌肽类抗体是抗线粒体腺嘌呤核苷酸转移酶抗体(anti-ANT)、抗β1肾上腺素能受体抗体(anti-β1AR)、抗M2-胆碱能受体抗体(anti-M2)和抗肌球蛋白重链抗体(anti-MHC)。这些抗体在VMC和DCM患者中均有较高的阳性检出率,可用于辅助诊断VMC和DCM。最近,肖华等发现在DCM患者的血液中存在一种新的抗L型钙离子通道自身抗体(CC-AAbs),该抗体在DCM患者中的阳性检出率显著高于正常对照组。那么在VMC患者体内是否也存在着这种抗L型钙通道自身抗体呢?其阳性率又如何?本研究旨在检测VMC患者血液中的抗L型钙通道抗体,探讨其对病毒性心肌炎的诊断价值。方法：收集在华中科技大学同济医学院附属协和医院心血管内科就诊和(或)住院的急性病毒性心肌炎(AVMC)、DCM患者各60例,并以60例健康献血者作为对照,采用酶联免疫吸附法(ELISA)检测三组受试者血清中的CC-AAbs,计算阳性率、灵敏度、特异度、符合率。结果：AVMC组、DCM组CC-AAbs的阳性率分别为95%、96.7%,明显高于健康对照组的6.7%(p值均0.01),CC-AAbs对AVMC检测的灵敏度、特异度与符合率分别为95%、93.3%、94.2%,CC-AAbs对DCM检测的灵敏度、特异度与符合率分别为96.7%、93.3%、95%。结论：AVMC患者体内也存在CC-AAbs。CC-AAbs在AVMC、DCM中的阳性率显著高于健康对照组。CC-AAbs对AVMC、DCM检测的灵敏度、特异度与符合率均较高,可用于辅助诊断病毒性心脏病。第二部分单独和联合检测抗心肌抗体诊断病毒性心脏病目的：开发并验证一种高灵敏度和高特异度的抗心肌抗体(AHA)检测试剂盒,探讨单独和联合检测AHA对病毒性心脏病(VHD)的诊断价值。方法：合成具有抗原决定簇的心肌线粒体腺嘌呤核苷酸转运体(／ANT)、β1肾上腺素能受体(p1-AR)、肌球蛋白重链(MHC)、L-型钙离子通道(L-CC)的多肽,制成相应的AHA检测试剂盒,用酶联免疫吸附法(ELISA)检测急性病毒性心肌炎(AVMC)患者(78例)、扩张型心肌病(DCM)患者(85例)、其他心脏病患者及健康体检者(共80例)血清中的四种AHA,以临床诊断参考标准为金标准,计算这四种AHA诊断AVMC、DCM的灵敏度、特异度、符合率,并行kappa一致性检验。结果：抗ANT抗体诊断AVMC的灵敏度、特异度、符合率分别为93.6%、87.5%、90.5%,与临床诊断比较,kappa值为0.81,P值0.01；抗β1-AR抗体诊断AVMC的灵敏度、特异度、符合率分别为97.4%、75.0%、86.1%,与临床诊断比较,kappa值为0.72,P值0.01；抗MHC抗体诊断AVMC的灵敏度、特异度、符合率分别为87.2%、82.5%、84.8%,与临床诊断比较,kappa值为0.70,P值0.01；抗L-CC抗体诊断AVMC的灵敏度、特异度、符合率分别为97.4%、66.3%、81.0%,与临床诊断比较,kappa值为0.63,P值0.01。抗ANT抗体诊断DCM的灵敏度、特异度、符合率分别为85.9%、87.5%、86.7%,与临床诊断比较,kappa值为0.73,P值0.01；抗β1-AR抗体诊断DCM的灵敏度、特异度、符合率分别为96.5%、75.0%、86.1%,与临床诊断比较,kappa值为0.72,P值0.01；抗MHC抗体诊断DCM的灵敏度、特异度、符合率分别为92.9%、82.5%、87.9%,与临床诊断比较,kappa值为0.76,P值0.01；抗L-CC抗体诊断DCM的灵敏度、特异度、符合率分别为97.6%、66.3%、82.4%,与临床诊断比较,kappa值为0.65,P值0.01。若同一份血清四种AHA均阳性诊断AVMC的灵敏度、特异度、符合率分别为78.2%、92.5%、85.4%,与临床诊断比较,kappa值为0.71,P值0.01。同一份血清四种AHA均阳性诊断DCM的灵敏度、特异度、符合率分别为82.4%、92.5%、87.3%,与临床诊断比较,kappa值为0.75,P值0.01。结论：我们自主研发的系列AHA试剂盒检测AVMC和DCM的结果与其临床诊断具有高度一致性,可作为VHD的辅助诊断指标。单独检测时anti-ANT对AVMC的诊断价值最高,anti-MHC对DCM的诊断价值最高,四种抗体联合检测能提高诊断的特异度。
[Abstract]:Part 1 Determination of anti calcium channel antibody in patients with viral myocarditis
Objective: Many studies have shown that viral myocarditis (VMC) and dilated cardiomyopathy (DCM) are related to viral infection and subsequent autoimmune response, so some scholars call them viral heart disease (VHD). Previous studies have found that there are many kinds of anti-myocardial autoantibodies (AHA) in patients with VHD, of which four are internationally recognized anti-myocardial autoantibodies. Cardiac peptide antibodies are anti-mitochondrial adenine nucleotide transferase antibodies (anti-ANT), anti-beta-1-adrenergic receptor antibodies (anti-beta 1AR), anti-M2-cholinergic receptor antibodies (anti-M2) and anti-myosin heavy chain antibodies (anti-MHC). These antibodies have high positive detection rates in VMC and DCM patients and can be used to assist the diagnosis of VMC and DCM. Recently, Xiao Hua et al. found a new anti-L-type calcium channel autoantibody (CC-AAbs) in the blood of patients with DCM. The positive rate of CC-AAbs in patients with DCM was significantly higher than that in normal control group. Objective to investigate the diagnostic value of anti L type calcium channel antibody in patients with MC.
Methods: 60 patients with acute viral myocarditis (AVMC) and 60 patients with DCM were enrolled in the Department of Cardiovascular Medicine, Union Medical College Affiliated to Tongji Medical College, Huazhong University of Science and Technology, and 60 healthy blood donors were used as control group. The serum CC-AAbs were detected by enzyme-linked immunosorbent assay (ELISA). Dissimilarity, coincidence rate.
Results: The positive rates of CC-AAbs in AVMC group and DCM group were 95%, 96.7%, significantly higher than 6.7% in healthy control group (p 0.01). The sensitivity, specificity and coincidence rate of CC-AAbs to AVMC were 95%, 93.3%, 94.2% respectively. The specificity and coincidence rate of CC-AAbs to DCM were 96.7%, 93.3% and 95% respectively.
Conclusion: The positive rate of CC-AAbs. CC-AAbs in AVMC patients is significantly higher than that in healthy controls. CC-AAbs has higher sensitivity, specificity and coincidence rate in detecting AVMC and DCM, and can be used as an auxiliary diagnostic tool for viral heart disease.
The second part is the separate and joint detection of anti myocardial antibodies in the diagnosis of viral heart disease.
Objective: To develop and validate a high sensitivity and specificity test kit for detecting anti-myocardial antibody (AHA), and to explore the diagnostic value of single and combined detection of AHA for viral heart disease (VHD).
METHODS: Polypeptides of adenine nucleotide transporter (/ANT), beta-1-adrenergic receptor (p1-AR), myosin heavy chain (MHC), L-type calcium channel (L-CC) with antigenic determinants were synthesized, and the corresponding AHA kits were made. 78 patients with acute viral myocarditis (AVMC) were detected by enzyme-linked immunosorbent assay (ELISA). Four kinds of AHA in serum of 85 patients with dilated cardiomyopathy (DCM), 80 patients with other heart diseases and 80 healthy persons were calculated according to the clinical diagnostic reference standard. The sensitivity, specificity and coincidence rate of the four AHA in diagnosis of AVMC and DCM were calculated and the kappa consistency test was performed.
Results: The sensitivity and specificity of anti-ANT antibody in the diagnosis of AVMC were 93.6%, 87.5% and 90.5%, respectively. Compared with clinical diagnosis, the kappa value was 0.81, P value was 0.01; the sensitivity and specificity of anti-beta 1-AR antibody in the diagnosis of AVMC were 97.4%, 75.0%, 86.1%, respectively. The sensitivity, specificity and coincidence rate were 87.2%, 82.5% and 84.8% respectively. Compared with clinical diagnosis, the kappa value was 0.70 and P value was 0.01. The sensitivity, specificity and coincidence rate of anti-L-CC antibody in diagnosis of AVMC were 97.4%, 66.3% and 81.0% respectively. Compared with clinical diagnosis, the kappa value was 0.63 and P value was 0.01. Compared with clinical diagnosis, the kappa value was 0.73, P value was 0.01; the sensitivity and specificity of anti-beta-1-AR antibody were 96.5%, 75.0%, 86.1%, respectively. Compared with clinical diagnosis, the kappa value was 0.72, P value was 0.01; the sensitivity and specificity of anti-MHC antibody in diagnosis of DCM were 92.9%, 82.5%, 87.9%, respectively. The sensitivity and specificity of anti-L-CC antibody were 97.6%, 66.3% and 82.4%, respectively. Compared with clinical diagnosis, the kappa value was 0.65 and the P value was 0.01. The sensitivity, specificity and coincidence rate of four kinds of AHA in the same serum were 82.4%, 92.5% and 87.3% respectively. Compared with clinical diagnosis, the kappa value was 0.75 and P value was 0.01.
Conclusion: The results of our series of AHA kits for detecting AVMC and DCM are highly consistent with their clinical diagnosis and can be used as an auxiliary diagnostic index for VHD.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R541

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