抗乙酰胆碱受体抗体和抗肌肉特异性酪氨酸激酶抗体双阳性重症肌无力的临床特征与转归

Clinical characteristics and outcomes of myasthenia gravis patients with double positive antibodies against acetylcholine receptor and muscle-specific tyrosine kinase

目的探讨抗乙酰胆碱受体抗体(AChR-Ab)和抗肌肉特异性酪氨酸激酶(MuSK-Ab)双阳性重症肌无力(MG)的临床表现、治疗特点及转归。方法回顾2017年8月至2020年11月在中山大学附属第一医院住院的MG患者,共纳入34例MuSK-Ab阳性MG(MuSK-MG)患者、11例双抗体阳性MG(double-antibodies positive MG,DP-MG)和80例AChR-Ab阳性MG(AChR-MG)患者。收集3组患者的临床资料,利用统计学分析DP-MG患者在人口学特征、临床表现和治疗转归等方面与AChR-MG患者和MuSK-MG患者的差异。结果DP-MG组患者的女性比例为7/11,男性比例为4/11,发病年龄为(41±27)年,与AChR-MG组性别分布比较差异有统计学意义(P<0.05)。DP-MG组和MuSK-MG组眼外肌受累的比例(8/11和52.9%)低于AChR-MG组(83.8%)(均P<0.05)。DP-MG组和MuSK-MG组肌无力危象发生率(6/11和61.8%)高于AChR-MG组(20.0%)(P<0.05)。DP-MG组和MuSK-MG组新斯的明试验阳性率(8/11和74.2%)低于AChR-MG组(96.8%),DP-MG组低频重复神经电刺激(RNS)阳性率(5/10)低于AChR-MG组(85.1%)(均P<0.05)。MuSK-Ab滴度与病程呈正相关(r=0.466,P<0.05),症状改善后抗体滴度下降。DP-MG组和MuSK-MG组患者对胆碱酯酶抑制剂的反应性(2/11和9.1%)低于AChR-MG组(66.3%),且两组患者服药后不良反应发生率(5/11和39.4%)高于AChR-MG组(15.0%)(均P<0.05)。4例DP-MG患者术后病理结果显示胸腺增生和胸腺瘤各2例。后续随访发现5例(5/11)DP-MG患者达到最轻微表现状态及以上更好状态。结论DP-MG患者的性别分布、发病年龄、药理学特征和电生理检查与MuSK-MG类似,但DP-MG患者病情严重程度介于AChR-MG和MuSK-MG之间。

Objective To investigate the clinical manifestations,treatment characteristics and outcomes of myasthenia gravis(MG)dually positive for anti-acetylcholine receptor antibody(AChR-Ab)and anti-muscle-specific tyrosine kinase antibody(MuSK-Ab).Method MG patients hospitalized in the First Affiliated Hospital of Sun Yat-sen University from August 2017 to November 2020 were retrospectively collected.Thirty-four MuSK-Ab positive MG(MuSK-MG)patients,11 double-antibodies positive MG(DP-MG)patients,and 80 AChR-Ab positive MG(AChR-MG)patients were included and allocated to three different groups.The clinical data of patients in the three groups were collected,and the differences of demographic characteristics,clinical manifestations and treatment outcomes between DP-MG patients and AChR-MG and MuSK-MG patients were analyzed.Result The proportion of female and male patients in DP-MG group was 7/11 and 4/11 respectively,and the onset age of DP-MG was(41±27)years.The difference in gender distribution between DP-MG and AChR-MG groups was statistically significant(P<0.05).The proportion of extraocular muscle involvement in the DP-MG and MuSK-MG groups(8/11 and 52.9%)was lower than that in the AChR-MG group(83.8%),and the difference was statistically significant(P<0.05).The incidence of myasthenia crisis in DP-MG and MuSK-MG groups(54.5% and 61.8%)were higher than that in AChR-MG group(20.0%),with astatistically significant difference(P<0.05).The positive rate of neostigmine test in DP-MG and MuSK-MG groups(8/11 and 74.2%)were lower than that of AChR-MG group(96.8%),and the positive rate of low frequency repetitive nerve stimulation(RNS)in DP-MG group(5/10)was lower than that in AChR-MG group(85.1%),with statistically significant differences(all P<0.05).MuSK-Ab titer was positively correlated with the course of disease(r=0.466,P<0.05),and antibody titer decreased after symptom improvement(P<0.05).The response of patients in DP-MG and MuSK-MG groups to cholinesterase inhibitors(2/11 and 9.1%)was worse than that in the AChR-MG group(66.3%),and the incidence of side effects in the two groups(5/11 and 39.4%)was higher than that in the AChR-MG group(15.0%),with statistically significant differences(all P<0.05).There were 4 DP-MG patients underwent thymectomy,and the pathological results detected two cases of thymoma and two cases of thymic hyperplasia.Subsequent follow-up showed that 5(5/11)DP-MG patients achieved minimal manifestation status or better status.Conclusion The gender distribution,age of onset,pharmacological characteristics and electrophysiological examination of DP-MG patients were similar to those of MuSK-MG patients,but the severity of DP-MG patients was between that of AChR-MG and MuSK-MG patients.