乙酰胆碱受体抗体簇在血清阴性重症肌无力诊断中的临床特征和诊断价值。
Clinical Features and Diagnostic Usefulness of Antibodies to Clustered Acetylcholine Receptors in the Diagnosis of Seronegative Myasthenia Gravis.
机构信息
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England2Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, England.
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
出版信息
JAMA Neurol. 2015 Jun;72(6):642-9. doi: 10.1001/jamaneurol.2015.0203.
IMPORTANCE
Cell-based assays (CBAs) were shown to improve detection of acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG). Herein, we asked whether these assays were able to help determine the diagnosis in patients studied in routine clinical practice.
OBJECTIVES
To determine the diagnostic usefulness of CBAs in the diagnosis of MG and to compare the clinical features of patients with antibodies only to clustered AChRs with those of patients with seronegative MG (SNMG).
DESIGN, SETTING, AND PARTICIPANTS: All patients with clinical suspicion of MG who were seen within the Division of Clinical Neurology at the John Radcliffe Hospital in Oxford, England, between November 1, 2009, and November 30, 2013. Their serum antibodies and clinical features were studied.
EXPOSURES
Radioimmunoprecipitation assay (RIPA) and CBA were used to test for standard AChR antibodies and antibodies to clustered AChRs in 138 patients. All available samples from patients with SNMG were retrospectively tested for lipoprotein receptor-related protein 4 (LRP4) antibodies.
MAIN OUTCOMES AND MEASURES
Demographic, clinical, neurophysiological, and laboratory data.
RESULTS
In total, 138 patients were tested for antibodies to clustered AChRs, and 42 had a final diagnosis of MG. The clustered AChR CBA detected antibodies in 38.1% (16 of 42) of RIPA-negative patients with MG with 100% specificity. All patients with SNMG who were tested for LRP4 antibodies (21 of 26) were negative by CBA. Compared with patients with SNMG, patients with antibodies only to clustered AChRs had frequent prepubertal onset (62.5% [median age, 6 years; age range, 1-52 years] vs 11.5% [median age, 38 years; age range, 2-72 years], P ≤ .05), high prevalence of ocular MG (62.5% vs 42.3%), milder disease severity with less bulbar involvement (25.0% vs 46.2%), and absence of respiratory symptoms (0% vs 23.1%). Response to treatment and prognosis was good, with a reduced need for thymectomy (6.3% vs 19.2%) and a high proportion of patients going into remission (50.0% vs 8.3%, P ≤ .05). These observations also apply to the classic AChR MG phenotype seen in large series.
CONCLUSIONS AND RELEVANCE
Cell-based assay is a useful procedure in the routine diagnosis of RIPA-negative MG, particularly in children. Patients with antibodies only to clustered AChRs appear to be younger and have milder disease than other patients with MG. These observations will have implications in planning treatment.
重要性
细胞基础检测（C BA）被证明可以提高重症肌无力（MG）患者乙酰胆碱受体（AChR）抗体的检测率。在此，我们研究了这些检测方法是否有助于确定在常规临床实践中接受检查的患者的诊断。
目的
确定 C BA 在 MG 诊断中的应用价值，并比较仅针对聚集 AChR 抗体的患者与血清阴性 MG（SNMG）患者的临床特征。
设计、地点和参与者：所有 2009 年 11 月 1 日至 2013 年 11 月 30 日期间在英国牛津约翰拉德克利夫医院临床神经病学系就诊且临床怀疑患有 MG 的患者。研究了他们的血清抗体和临床特征。
暴露因素
使用放射免疫沉淀试验（RIPA）和 C BA 检测 138 例患者的标准 AChR 抗体和聚集 AChR 抗体。对所有 SNMG 患者的可用样本进行回顾性检测脂蛋白受体相关蛋白 4（LRP4）抗体。
主要结局和测量指标
人口统计学、临床、神经生理学和实验室数据。
结果
共有 138 例患者接受了聚集 AChR 抗体检测，其中 42 例最终诊断为 MG。聚集 AChR C BA 在 100%特异性的情况下，在 38.1%（42 例中的 16 例）RIPA 阴性的 MG 患者中检测到抗体。所有接受 LRP4 抗体 C BA 检测的 SNMG 患者（26 例中的 21 例）均为阴性。与 SNMG 患者相比，仅针对聚集 AChR 抗体的患者发病年龄更早（62.5%[中位数年龄 6 岁；年龄范围 1-52 岁] vs 11.5%[中位数年龄 38 岁；年龄范围 2-72 岁]，P≤.05），眼肌型 MG 患病率更高（62.5% vs 42.3%），疾病严重程度较轻且延髓受累较少（25.0% vs 46.2%），无呼吸症状（0% vs 23.1%）。治疗反应和预后良好，需要胸腺切除术的患者减少（6.3% vs 19.2%），进入缓解期的患者比例较高（50.0% vs 8.3%，P≤.05）。这些观察结果也适用于大型系列中观察到的经典 AChR MG 表型。
结论和相关性
C BA 是 RIPA 阴性 MG 常规诊断中的一种有用程序，特别是在儿童中。仅针对聚集 AChR 抗体的患者似乎比其他 MG 患者年龄更小，疾病更轻。这些观察结果将对治疗计划产生影响。
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