Marino Mariapaola, Scuderi Flavia, Samengo Daniela, Saltelli Giorgia, Maiuri Maria Teresa, Shen Chengyong, Mei Lin, Sabatelli Mario, Pani Giovambattista, Antonini Giovanni, Evoli Amelia, Bartoccioni Emanuela
Institute of General Pathology, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
Department of Laboratory Medicine, School of Medicine, Università Cattolica S. Cuore, Rome, Italy.
PLoS One. 2015 Aug 18;10(8):e0135378. doi: 10.1371/journal.pone.0135378. eCollection 2015.
Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoantibodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4 (LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG.
The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system.
We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals.
Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis.
重症肌无力（MG）是一种自身免疫性疾病，90%的患者具有针对肌肉型烟碱型乙酰胆碱受体（AChR）的自身抗体，而在其余10%患者中的半数（5%）检测到了针对肌肉特异性酪氨酸激酶（MuSK）的自身抗体。最近，被鉴定为聚集蛋白受体的低密度脂蛋白受体相关蛋白4（LRP4），在相当一部分双血清阴性（dSN）重症肌无力患者中被认为是第三个自身免疫靶点，其频率因检测人群的不同方法和来源国而异。也有令人信服的实验证据表明抗LRP4自身抗体可能导致重症肌无力。
本研究的目的是检测101例意大利重症肌无力患者（55例dSN、23例AChR阳性和23例MuSK阳性）、45名健康献血者和40例其他神经系统疾病患者作为对照中抗LRP4自身抗体的存在情况及其诊断意义。所有血清均采用基于转染LRP4的HEK293T细胞的细胞抗原检测法以及流式细胞荧光检测系统进行分析。
我们发现dSN-MG组的阳性率为14.5%（8/55），AChR和MuSK阳性患者中同时出现的频率为13%（3/23）；此外，我们报告LRP4阳性的dSN-MG个体中年轻女性患病率较高，疾病形式较轻。
我们的数据证实LRP4是一个新的自身免疫靶点，支持在重症肌无力的进一步研究中纳入抗LRP4抗体的价值。
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