Pasnoor Mamatha, Heim Andrew J, Herbelin Laura, Statland Jeffrey, Dimachkie Mazen M, Becker Mara, Barohn Richard J
University of Kansas Medical Center, Department of Neurology, Kansas City, KS.
Duke University School of Medicine, Division of Rheumatology, Durham, NC.
Kans J Med. 2020 Feb 26;13(Suppl 2):10-13. eCollection 2020.
Methotrexate (MTX) is an immunosuppressive and anti-inflammatory drug used to treat rheumatoid arthritis (RA) and other autoimmune conditions. MTX is transported into cells, where glutamate moieties are added and is retained as methotrexate polyglutamates (MTXPGs). In the RA literature, it has been reported that the degree of polyglutamation correlates with the anti-inflammatory effect of MTX in RA. There are no prior studies evaluating the relationship between MTXPGs and myasthenia gravis (MG) outcome measures. The objective of this study was to assess the correlation between methotrexate (MTX) polyglutamates (MTXPGs) with Myasthenia Gravis (MG) outcome measures.
An analysis was done of blood drawn from patients enrolled in the 12-month randomized, placebo-controlled study of MTX in MG study. Red blood cell MTXPGs were measured via ultra-performance liquid chromatography and tandem mass spectrometry. MTXPG was correlated to MG outcome measures using Spearman Correlation Coefficient. A two-group t-test was used to determine the difference in MTXPG based on clinical outcome responder definitions.
Twenty-one polyglutamate samples were analyzed of subjects on MTX while eight samples were analyzed from subjects on placebo. Pentaglutamate had the strongest correlation with the MG-ADL (0.99), while tetraglutamate had the strongest correlation with the QMG (0.54). Triglutamate had the strongest correlation with MGC (0.76).
There were variable correlations between MTXPG and MG outcomes (rho range: 0.08 to 0.99). There are strong correlations between MTXPG and the MG-ADL, QMG, and MGC. Long chain methotrexate polyglutamates correlate better with MG outcomes.
甲氨蝶呤（MTX）是一种免疫抑制和抗炎药物，用于治疗类风湿性关节炎（RA）和其他自身免疫性疾病。MTX被转运到细胞内，在那里添加谷氨酸部分并以甲氨蝶呤多聚谷氨酸盐（MTXPGs）的形式保留下来。在RA文献中，已有报道称多聚谷氨酸化程度与MTX在RA中的抗炎作用相关。此前尚无研究评估MTXPGs与重症肌无力（MG）预后指标之间的关系。本研究的目的是评估甲氨蝶呤（MTX）多聚谷氨酸盐（MTXPGs）与重症肌无力（MG）预后指标之间的相关性。
对参加MTX治疗MG的12个月随机、安慰剂对照研究的患者所抽取的血液进行分析。通过超高效液相色谱和串联质谱法测量红细胞MTXPGs。使用Spearman相关系数将MTXPG与MG预后指标进行关联。采用两组t检验根据临床结局反应者定义确定MTXPG的差异。
对21份服用MTX受试者的多聚谷氨酸样本进行了分析，同时对8份服用安慰剂受试者的样本进行了分析。五聚谷氨酸与MG-ADL的相关性最强（0.99），而四聚谷氨酸与QMG的相关性最强（0.54）。三聚谷氨酸与MGC的相关性最强（0.76）。
MTXPG与MG结局之间存在不同程度的相关性（rho范围：0.08至0.99）。MTXPG与MG-ADL、QMG和MGC之间存在强相关性。长链甲氨蝶呤多聚谷氨酸盐与MG结局的相关性更好。
