不同原发疾病所致心衰患者中β_3肾上腺素受体自身抗体的检测意义

Clinical Implication for Detection of Autoantibodies against Beta 3-adrenoceptor in Patients with Heart Failure

目的检测不同原发疾病所致心衰患者血清中的β_3肾上腺素受体自身抗体(β_3-AAB)的类别,并分析其可能的医学意义。方法以合成的β_3肾上腺素受体细胞外第二环肽段作为抗原,应用酶联免疫吸附实验,检测临床甄选的160例扩心病、冠心病、高心病和风心病所致心衰病患者及100例健康正常对照者血清中IgG和IgM类β_3-AAB的阳性率及抗体水平,并分析它们对患者心功能的影响。结果部分心衰患者和正常对照血清中存在Igc和/或IgM类β_3-AAB。扩心病所致心衰患者血清中,IgG类β_3-AAB的阳性率和抗体水平均显著高于正常对照(40.0% vs 8.0%,P<0.01和1.18±0.29 vs 0.92±0.20,P<0.05);IgM类β_3-AAB阳性率也显著高于正常人(53.3% vs 12.0%,P<0.01),但其抗体水平与正常对照相比差异无统计学意义(0.52±0.08 vs 0.52±0.09,P>0.05)。冠心病所致心衰患者血清中,IgG类β_3-AAB阳性率也显著高于正常人(25.6% vs 8.0%,P<0.01),但其抗体水平与正常对照相比差异无统计学意义(1.02±0.17 vs 0.92±0.20,P>0.05)。而高心病和风心病所致心衰患者血清中,IgG类β_3-AAB的阳性率(20.0%和30.0%)和抗体水平(0.96±0.11和0.96±0.19)以及IsM类β_3- AAB的阳性率(16.7%和20.0%)和抗体水平(0.51±0.05和0.48±0.04)与相应正常对照比较,差异无统计学意义(P>0.05)。正常对照Igc类β_3-AAB水平明显高于IgM类(0.92±0.20 vs 0.52±0.09,P<0.01),各心衰组有相同的规律。IgG类β_3-AAB对心衰患者左室射血分数有显著影响(F=6.178,P=0.014),进一步分析发现,扩心病患者Igc类β_3-AAB阳性者心脏左室射血分数明显高于阴性者(25.1±2.9 vs 15.5±1.6,P<0.01)。结论IgG类β_3-AAB可能是重要的功能性抗体,主要参与扩心病患者心衰的病理生理过程。

Objective To investigate the immunoglobulin fractions of sera from healthy subjects and patients with heart failure for the presence of autoantibodies against the beta3 - adrenoceptor （ β3- AAB ） and their possible clinical implication. Methods The synthetic peptide of the second extracellular loop of the beta3 - adrenoeeptor was used as the antigen to screen sera from patients with heart faihtre （n = 160） and healthy blood donors （ n = 100） as controls. Results β3 - AABs were present in parts of patients with heart failure and healthy controls. In heart failure patients with dilated cardiomyopathy （DCM） , the frequency and responses of IgG isotype of β3 - AAB were significantly higher than those of control group （40. 0% vs 8.0% , P 〈 0. 01 and 1.18 ± 0. 29 vs 0. 92 ± 0. 20, P 〈 0. 05, respectively）. The frequency of IgG isotype of β3- AAB in coronary heart disease （CHD） was also significantly higher than that of control group （25.6% vs 8.0% , P 〈 0. 01 ） , but the responses of them were similar to those of healthy controls （ 1.02 ± 0. 17 vs 0.92±0.20, P 〉 0. 05 ） . And β3 - AABs were not associated with heart failure secondary to valvular or hypertensive heart disease. Although a similar frequency of IgG and IgM antibodies had been shown, statistically raised reactivity of IgG compared to IgM appeared in controls （0. 92 ± 0. 20 vs 0. 52 ± 0.09, P 〈 0. 01 ） and implied that the predominant response to the antigen was IgG. The heart function of patients with heart failure, expressed by ejection fraction （EF） of left ventricle, was significantly affected by IgG isotype of β3 -AAB （F = 6. 178, P =0. 014）. Additionally, EF values of patients with DCM, who were positive for β3- AAB IgG, were higher than those of negtive ones （25.1 ± 2.9 vs 15.5± 1.6, P 〈 0.01 ）. Conclusion These findings indicated that the autoantibodies against the human beta3 - adrenoceptors may participate in the pathophysiological changes in patients with heart failure, especially in DCM. The mechanisms by which the autoantibodies against the beta3 - adrenoceptors affect the pathogenesis of heart failure need to be further explored.