Anti-agrin autoantibodies in myasthenia gravis
Anti-agrin autoantibodies in myasthenia gravis
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DOI：
10.1212/wnl.0000000000000478
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发表时间：
2014-06-03
期刊：
影响因子：
9.9
通讯作者：
Kroeger, Stephan
中科院分区：
文献类型：
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作者：
Gasperi, Christiane;Melms, Arthur;Kroeger, Stephan
目的：由于细胞外基质蛋白agrin对神经肌肉连接的形成和维持至关重要，我们验证了重症肌无力（MG）患者血清中存在抗agrin自身抗体的假设。方法：采用纯化的微型agrin蛋白固相ELISA法检测54例广泛性MG患者血清中抗agrin抗体的存在。54份血清中有30份血清抗乙酰胆碱受体（AChR）或肌肉特异性酪氨酸激酶（MuSK）抗体阴性，15份血清抗MuSK水平升高，9份血清抗AChR自身抗体水平升高。健康志愿者的16份血清作为对照。结果：鉴定出5种抗agrin抗体水平升高的血清。抗体的浓度在0.04 ~ 0.12 nM之间。5例agrin阳性血清中有4例抗musk阳性，1例抗achr阳性，2例抗低密度脂蛋白受体相关蛋白4 （LRP4）自身抗体水平升高。一些血清染色成年小鼠神经肌肉连接处，并与293HEK细胞中表达的天然mini-agrin反应。结论：研究结果为agin作为MG患者自身抗体的新靶点蛋白提供了证据。抗agrin抗体总是与针对musk、LRP4或achr的自身抗体联合检测，表明在agrin阳性MG病例中，针对几种神经肌肉蛋白的自身抗体发生率很高。
Objective: Because the extracellular matrix protein agrin is essential for neuromuscular junction formation and maintenance, we tested the hypothesis that autoantibodies against agrin are present in sera from patients with myasthenia gravis (MG).Methods: We determined the presence of anti-agrin antibodies in 54 sera from patients with generalized MG using a solid-phase ELISA with purified mini-agrin protein. Thirty of the 54 sera were seronegative for antibodies against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK), 15 had elevated levels of anti-MuSK, and 9 had elevated levels of anti-AChR autoantibodies. Sixteen sera from healthy volunteers served as control.Results: Five sera with elevated levels of anti-agrin antibodies were identified. The concentration of the antibodies ranged between 0.04 and 0.12 nM. Four of the 5 agrin-positive sera were also positive for anti-MuSK, one was positive for anti-AChR, and 2 had elevated levels of anti-low-density lipoprotein receptor-related protein 4 (LRP4) autoantibodies. Some of the sera stained adult mouse neuromuscular junctions and reacted with native mini-agrin expressed in 293HEK cells.Conclusions: The results provide evidence for agrin as a novel target protein for autoantibodies in patients with MG. Anti-agrin antibodies were always detected in combination with autoantibodies againstMuSK, LRP4, or AChRs, indicating a high incidence of autoantibodies against several neuromuscular proteins in the agrin-positive MG cases.