肌肉特异性激酶(MuSK)-重症肌无力(MG)由针对MuSK的致病性自身抗体引起,其与疾病严重程度相关并且主要属于IgG4亚类。MuSK-MG的一线治疗是皮质类固醇的一般免疫抑制,但治疗对IgG4和MuSKIgG4水平的影响尚未研究。
■我们分析了52例MuSK-MG患者(45例女性,7男,来自意大利的中位年龄49岁(17-79岁),荷兰,希腊和比利时,和43名AChR-MG患者(22名女性,21男,来自意大利的中位年龄63岁(范围2-82岁),接受不同类型的免疫抑制,和来自46个年龄和性别匹配的非疾病对照的血清(没有诊断出的疾病,38女,8男,来自荷兰的中位年龄51.5(范围20-68岁)。我们分析了疾病的严重程度(通过MGFA或QMG评分评估),并测量了MuSKIgG4,MuSKIgG的浓度,通过ELISA检测血清中的总IgG4和总IgG,RIA和比浊法。
■我们观察到,MuSK-MG患者在治疗后表现出强劲的临床改善和MuSKIgG减少,以及MuSKIgG4浓度,但不是总的IgG4浓度,与临床严重程度相关。MuSKIgG和MuSKIgG4浓度在4/5个体免疫抑制后降低,但来自非关联患者样本的数据显示没有差异.总血清IgG4水平在正常范围内,在1/52MuSK-MG中IgG4水平高于阈值(1.35g/L),2/43AChR-MG患者和1/45非疾病对照。MuSK-MG患者在发病后的前四年内有所改善,但是四年后观察到MuSKIgG4没有进一步的临床改善或减少,总共只有14/52(26.92%)的患者,其中13人(93.3%)接受了一般免疫抑制,达到临床缓解。
■我们得出的结论是,MuSK-MG患者在一般免疫抑制的情况下在临床上有所改善,但可能需要进一步治疗才能达到缓解。个体患者的纵向测试在临床上可能比MuSKIgG4的单次测量更有用。在随访期间,AChR和MuSK-MG患者之间的血清IgG4浓度和IgG4/IgG比率没有发现显着差异。有必要对更大的患者和对照组进行进一步的研究以验证研究结果。
UNASSIGNED: Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK
IgG4 levels has not been studied.
UNASSIGNED: We analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17-79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2-82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20-68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total
IgG4 and total IgG in the sera by ELISA, RIA and nephelometry.
UNASSIGNED: We observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total
IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum
IgG4 levels were within the normal range, with
IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission.
UNASSIGNED: We conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum
IgG4 concentrations and
IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings.