抗髓鞘相关糖蛋白抗体阳性IgM相关性周围神经病11例临床分析

Anti-myelin-associated glycoprotein antibody positive IgM monoclonal gammopathy related peripheral neuropathy:11 cases and literature review

目的提高对罕见的抗髓鞘相关糖蛋白(MAG)抗体阳性的IgM相关性周围神经病(IgM-PN)的认识。方法总结2014年1月至2019年4月北京协和医院诊断的11例抗MAG抗体阳性的IgM-PN患者的临床特点、实验室检查、治疗方案和预后。结果11例患者中,男8例,女3例,中位发病年龄63(52~77)岁。其中9例患者以远端肢体麻木起病,6例伴肌力减退。神经传导速度检查示,均为周围神经脱髓鞘损害,以下肢感觉神经损害为主,6例伴慢性轴索损害。11例患者均存在血清IgM型单克隆免疫球蛋白,6例为IgMκ型,3例为IgMλ型,2例为IgMκ/IgGκ双克隆型。3例患者继发于巨球蛋白血症。11例患者的血清抗MAG抗体均为阳性。9例患者接受利妥昔单抗单药或联合化疗,治疗后7例患者的神经症状稳定或改善。结论抗MAG抗体阳性的IgM-PN是一种罕见的M蛋白相关性疾病。对于伴IgM型M蛋白的周围神经病患者,应常规筛查抗MAG抗体。基于利妥昔单抗的治疗可作为其一线治疗方案。

Objective To improve the understanding of rare anti-myelin-associated glycoprotein(MAG)positive IgM monoclonal gammopathy related peripheral neuropathy(IgM-PN).Methods Eleven cases of IgM paraproteinemia and anti-MAG antibody positive neuropathy diagnosed since 2014 in Peking Medical Union College Hospital were summarized.The medical records including clinical manifestation,lab results,treatment and prognosis were analyzed.Results Among the 11 patients(8 male and 3 female),the median onset age is 63 years old(range from 52 to 77 years old).The peripheral neuropathy of 9 patients were characterized by distal onset of numbness,6 patients suffered from muscle weakness.The nerve conduction velocity study indicated that all 11 patients had demyelinating peripheral nerve damage,which was sensory predominant and more severe in lower limbs,6 of them had secondary axonal damage.Monoclonal IgM gammopathy was identified in all 11 patients,among which 6 were IgM κ,2 IgG κ and IgM κ bi-clonal,3 IgM λ.Three patients were diagnosed with Waldenström’s macroglobulinaemia.The anti-MAG-IgM antibody was positive in all 11 cases.After diagnosis,9 patients received combination chemotherapy including rituximab or rituximab treatment alone.The monoclonal IgM level declined significantly in 7 patients.The neuropathy was stable or improved.Conclusions Anti-MAG antibody positive IgM-PN is a rare M protein related disease.In peripheral neuropathy with undetermined etiology,we suggest to screen M protein and anti-MAG antibody.Chemotherapy including rituximab or rituximab alone is recommended as first-line therapy.