Xu B Y, Pirskanen R, Lefvert A K
Immunological Research Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
J Neuroimmunol. 1998 Nov 2;91(1-2):82-8. doi: 10.1016/s0165-5728(98)00159-3.
Patients with myasthenia gravis have antibodies and T cells that react with the beta1- and beta2-adrenergic receptors. These receptors, as well as other auto-antigens, are present on cardiomyocytes, skeletal muscle cells and lymphocytes and are of importance for the regulation of the functions of these organs. Antibodies against the beta1-adrenergic receptor have been implicated in dilated cardiomyopathies. Myasthenia gravis (MG) patients have been suggested to have a higher than normal prevalence of heart disease. We have analysed the isotypes, subclasses, and binding sites of the beta-adrenergic receptors antibodies in both MG patients and healthy individuals and the correlation between beta-adrenergic receptors antibodies and heart disease in MG patients. The patients have IgG antibodies that react with both beta1- and beta2-adrenergic receptors. The subclasses were predominantly IgG2 and IgG4. By using synthesised overlapping peptides representing the immunodominant regions on the receptors, it was shown that the antibodies bound to partially overlapping sites on both beta1- and beta2-adrenergic receptors, but not to peptides from the acetylcholine receptor. beta-adrenergic receptor antibodies were found in 34/125 MG patients. Seven out of these 34 patients had symptomatic heart disease, all seven were over 70 years of age and had arteriosclerotic heart disease. There was no difference in the prevalence of clinical heart disease in patients with and without beta-adrenergic receptor antibodies. However, patients with heart disease had significantly higher levels of antibodies than healthy individuals and other patients. Antibodies against beta-adrenergic receptors in patients with myasthenia gravis binds to both beta1- and beta2-adrenergic receptors and might be implicated in the few patients with myasthenia gravis who have heart disease.
重症肌无力患者体内存在与β1和β2肾上腺素能受体发生反应的抗体和T细胞。这些受体以及其他自身抗原存在于心肌细胞、骨骼肌细胞和淋巴细胞上，对这些器官功能的调节至关重要。针对β1肾上腺素能受体的抗体与扩张型心肌病有关。有研究表明重症肌无力（MG）患者患心脏病的几率高于正常水平。我们分析了重症肌无力患者和健康个体体内β肾上腺素能受体抗体的亚型、亚类和结合位点，以及重症肌无力患者体内β肾上腺素能受体抗体与心脏病之间的相关性。患者体内的IgG抗体可与β1和β2肾上腺素能受体发生反应。亚类主要为IgG2和IgG4。通过使用代表受体上免疫显性区域的合成重叠肽，结果显示这些抗体与β1和β2肾上腺素能受体上部分重叠的位点结合，但不与乙酰胆碱受体的肽段结合。在125例重症肌无力患者中有34例检测到β肾上腺素能受体抗体。这34例患者中有7例患有症状性心脏病，这7例患者均超过70岁，且患有动脉硬化性心脏病。有和没有β肾上腺素能受体抗体的患者临床心脏病患病率没有差异。然而，患有心脏病的患者抗体水平明显高于健康个体和其他患者。重症肌无力患者体内针对β肾上腺素能受体的抗体与β1和β2肾上腺素能受体均结合，可能与少数患有心脏病的重症肌无力患者有关。
