Song Tian, Chang Haoxiao, Du Li, Yin Linlin, Shi Fudong, Zhang Xinghu
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
China National Clinical Research Center for Neurological Diseases, Beijing, 100070, China.
Neurol Sci. 2020 Oct;41(10):2767-2771. doi: 10.1007/s10072-020-04376-8. Epub 2020 Apr 10.
Glucocorticoid (GC) is the first-line therapy in acute attacks of multiple sclerosis (MS), but its efficacy is individually variable and may be associated with glucocorticoid receptor (GR) gene.
To establish the association between GR gene sequence and clinical GC sensitivity in Chinese MS patients. And to investigate the expression differences of serum GRα and FK506 binding protein 5 (FKBP5) in GC responders and non-responders.
Coding exons 2-9 of the GR gene from 97 MS patients were sequenced. We performed ELISA to detect serum GRα and FKBP5 before the GC impulse therapy in patients with different GC sensitivities (according to the EDSS changes before and after the GC medication).
Seven new mutations were located in exon 2, but the presence or absence of mutations was not associated with the response to GC therapy (P = 0.416). The GC-sensitive patients had higher GRα (P = 0.011) but lower FKBP5 (P = 0.025) levels in the serum.
The GR mutations detected in our study were not associated with the response to GC in Chinese MS patients. Higher GRα and lower FKBP5 levels in the serum might predict the response to GC, which may provide potential therapeutic target for GC-resistant patients with acute MS attack.
糖皮质激素（GC）是多发性硬化症（MS）急性发作的一线治疗药物，但其疗效存在个体差异，可能与糖皮质激素受体（GR）基因有关。
在中国MS患者中建立GR基因序列与临床GC敏感性之间的关联。并研究GC反应者和无反应者血清GRα和FK506结合蛋白5（FKBP5）的表达差异。
对97例MS患者的GR基因编码外显子2-9进行测序。我们采用酶联免疫吸附测定法（ELISA）检测不同GC敏感性患者（根据GC用药前后的扩展残疾状态量表（EDSS）变化）在GC冲击治疗前的血清GRα和FKBP5。
在外显子2中发现7个新突变，但突变的有无与GC治疗反应无关（P = 0.416）。GC敏感患者血清中GRα水平较高（P = 0.011），但FKBP5水平较低（P = 0.025）。
我们研究中检测到的GR突变与中国MS患者对GC的反应无关。血清中较高的GRα和较低的FKBP5水平可能预测对GC的反应，这可能为急性MS发作的GC抵抗患者提供潜在的治疗靶点。
