Alexandre Guérémy, John Boudjarane, Emilie Alazard, Etienne Fortanier, José Boucraut, Norman Abbou, Aude-Marie Grapperon, Ludivine Kouton, Annie Verschueren, Emmanuelle Salort-Campana, Shahram Attarian, Emilien Delmont
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Our aim was to determine the frequency of the MYD88<sup>L256P</sup> mutation in chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) and multifocal motor neuropathy with conduction blocks (MMN) and to assess its potential effect on the phenotype of the neuropathy.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The MYD88<sup>L256P</sup> mutation was tested in the peripheral blood mononuclear cells of 79 CIDP, 35 MMN, and 57 controls with nonimmune mediated disorders. Disease severity was assessed on disability scores, neurofilament light chain dosages, motor unit counts, and sums of the sensory and motor amplitudes on electrodiagnostic tests.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The MYD88<sup>L256P</sup> mutation was more frequent in MMN patients (12/35, 34%; odds ratio 28 [95% confidence interval 4–1262]; <i>p</i> < 0.001) and in CIDP patients (15/79, 19%; OR 13 [95% confidence interval 2–561]; <i>p</i> < 0.001) than in controls (1/57, 2%). Patients with the MYD88<sup>L256P</sup> mutation were more likely to have an IgM monoclonal gammopathy (13/27 vs. 8/87, <i>p</i> = 0.001). The MYD88<sup>L256P</sup> mutation remains more frequent in CIDP and MMN patients, even if patients with IgM monoclonal gammopathy were excluded. All the other characteristics were similar, especially the severity of the disease and the efficacy of intravenous immunoglobulins.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The MYD88<sup>L256P</sup> mutation is frequent in CIDP and MMN patients, suggesting new pathophysiological hypotheses and new therapeutic approaches.</p>\n </section>\n </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 8","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70310","citationCount":"0","resultStr":"{\"title\":\"Frequency and Relevance of MYD88L256P Mutation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy\",\"authors\":\"Alexandre Guérémy, John Boudjarane, Emilie Alazard, Etienne Fortanier, José Boucraut, Norman Abbou, Aude-Marie Grapperon, Ludivine Kouton, Annie Verschueren, Emmanuelle Salort-Campana, Shahram Attarian, Emilien Delmont\",\"doi\":\"10.1111/ene.70310\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>The myeloid differentiation primary response 88 (MYD88) protein is involved in immune processes through the activation of the toll-like receptors and the interleukin-1 receptor. The acquired MYD88<sup>L256P</sup> mutation enhances its activity and promotes inflammatory pathways and autoimmune diseases. Our aim was to determine the frequency of the MYD88<sup>L256P</sup> mutation in chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) and multifocal motor neuropathy with conduction blocks (MMN) and to assess its potential effect on the phenotype of the neuropathy.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The MYD88<sup>L256P</sup> mutation was tested in the peripheral blood mononuclear cells of 79 CIDP, 35 MMN, and 57 controls with nonimmune mediated disorders. Disease severity was assessed on disability scores, neurofilament light chain dosages, motor unit counts, and sums of the sensory and motor amplitudes on electrodiagnostic tests.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The MYD88<sup>L256P</sup> mutation was more frequent in MMN patients (12/35, 34%; odds ratio 28 [95% confidence interval 4–1262]; <i>p</i> < 0.001) and in CIDP patients (15/79, 19%; OR 13 [95% confidence interval 2–561]; <i>p</i> < 0.001) than in controls (1/57, 2%). Patients with the MYD88<sup>L256P</sup> mutation were more likely to have an IgM monoclonal gammopathy (13/27 vs. 8/87, <i>p</i> = 0.001). The MYD88<sup>L256P</sup> mutation remains more frequent in CIDP and MMN patients, even if patients with IgM monoclonal gammopathy were excluded. 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引用次数: 0
摘要
髓样分化初级反应88 （MYD88）蛋白通过激活toll样受体和白细胞介素-1受体参与免疫过程。获得性MYD88L256P突变增强其活性，促进炎症途径和自身免疫性疾病。我们的目的是确定MYD88L256P突变在慢性炎症性脱髓鞘性多根神经病变（CIDP）和多灶性运动神经病变伴传导阻滞（MMN）中的频率，并评估其对神经病变表型的潜在影响。方法对79例CIDP、35例MMN和57例非免疫介导性疾病患者外周血单个核细胞进行MYD88L256P突变检测。通过残疾评分、神经丝轻链剂量、运动单位计数以及电诊断测试的感觉和运动振幅总和来评估疾病严重程度。结果MYD88L256P突变在MMN患者中更为常见(12/35,34%；优势比28[95%置信区间4-1262]；p < 0.001)和CIDP患者(15/79,19%；OR 13[95%置信区间2-561]；P < 0.001)比对照组（1/ 57,2 %）。MYD88L256P突变的患者更容易发生IgM单克隆γ病（13/27 vs 8/87, p = 0.001）。即使排除IgM单克隆伽玛病患者，MYD88L256P突变在CIDP和MMN患者中仍然更常见。所有其他特征相似，特别是疾病的严重程度和静脉注射免疫球蛋白的疗效。结论MYD88L256P突变在CIDP和MMN患者中较为常见，提示新的病理生理假说和新的治疗途径。
Frequency and Relevance of MYD88L256P Mutation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy
Background
The myeloid differentiation primary response 88 (MYD88) protein is involved in immune processes through the activation of the toll-like receptors and the interleukin-1 receptor. The acquired MYD88L256P mutation enhances its activity and promotes inflammatory pathways and autoimmune diseases. Our aim was to determine the frequency of the MYD88L256P mutation in chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) and multifocal motor neuropathy with conduction blocks (MMN) and to assess its potential effect on the phenotype of the neuropathy.
Methods
The MYD88L256P mutation was tested in the peripheral blood mononuclear cells of 79 CIDP, 35 MMN, and 57 controls with nonimmune mediated disorders. Disease severity was assessed on disability scores, neurofilament light chain dosages, motor unit counts, and sums of the sensory and motor amplitudes on electrodiagnostic tests.
Results
The MYD88L256P mutation was more frequent in MMN patients (12/35, 34%; odds ratio 28 [95% confidence interval 4–1262]; p < 0.001) and in CIDP patients (15/79, 19%; OR 13 [95% confidence interval 2–561]; p < 0.001) than in controls (1/57, 2%). Patients with the MYD88L256P mutation were more likely to have an IgM monoclonal gammopathy (13/27 vs. 8/87, p = 0.001). The MYD88L256P mutation remains more frequent in CIDP and MMN patients, even if patients with IgM monoclonal gammopathy were excluded. All the other characteristics were similar, especially the severity of the disease and the efficacy of intravenous immunoglobulins.
Conclusions
The MYD88L256P mutation is frequent in CIDP and MMN patients, suggesting new pathophysiological hypotheses and new therapeutic approaches.
期刊介绍：
The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).
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