Efficacy of Rituximab Combined with Methylprednisolone in the Treatment of Autoimmune Encephalitis and Its Effect on Peripheral Blood PD-1 and PD-L1
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摘要:
目的 探究利妥昔单抗联合甲强龙治疗自身免疫性脑炎（AE）的疗效及对外周血程序性死亡因子-1（PD-1）、程序性死亡因子配体-1（PD-L1）的影响。 方法 选取2019年2月至2022年7月期间昆明市儿童医院收治的60例AE患儿作为研究对象，按照随机数字表法分为观察组（n = 30）和对照组（n = 30）。对照组采用甲强龙治疗；观察组采用利妥昔单抗联合甲强龙治疗。2组均用药4周后进行评价。比较2组疗效、T淋巴细胞亚群、外周血PD-1、PD-L1水平、免疫球蛋白水平变化。 结果 观察组总有效率（90.00%）高于对照组（66.67%），P < 0.05；经过治疗后，观察组患儿CD3+、CD4+水平以及CD4+/CD8+显著高于对照组，CD8+水平低于对照组（P < 0.05），外周血PD-1、PD-L1高于对照组（P < 0.05），IgA、IgG、IgM水平低于对照组（P < 0.05）。 结论 利妥昔单抗联合甲强龙对AE疗效确切，可改善机体免疫功能，提高PD-1、PD-L1水平，可作为临床应用的指导。 -
关键词:
- 利妥昔单抗 /
- 甲强龙 /
- 自身免疫性脑炎 /
- 程序性死亡因子-1 /
- 程序性死亡因子配体-1
Abstract:Objective To investigate the efficacy of rituximab combined with methylprednisolone in the treatment of autoimmune encephalitis （AE） and its effect on programmed death factor-1 （PD-1） and programmed death factor ligand 1 （PD-L1） in peripheral blood. Methods A total of 60 patients with AE admitted to Kunming Children's hospital from February 2019 to July 2022 were selected as research subjects, and were divided into observation group （n = 30） and control group （n = 30） according to random number table. The control group was treated with methylprednisolone, and the observation group was treated with rituximab combined with methylprednisolone. Both groups were evaluated after 4 weeks of treatment. The curative effect, T lymphocyte subsets, peripheral blood PD-1, PD-L1 levels and immunoglobulin levels were compared between the two groups. Results The total effective rate of the observation group （90.00%） was higher than that of the control group （66.67%）, P < 0.05. After treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group, and the level of CD8+ was lower than that in the control group （P < 0.05）. PD-1 and PD-L1 in peripheral blood were higher than those in control group （P < 0.05）, and the levels of IgA, IgG and IgM in the control group were obviously lower than those in the control group （P < 0.05）. Conclusion Rituximab combined with methylprednisolone has a definite therapeutic effect on AE; it can improve the immune function of the body and increase PD-1 and PD-L1 levels. Our findings can be used as a guide for clinical application. -
表 1 2组一般资料比较（
$\bar x \pm s $ ）Table 1. Comparison of general data between the two groups （
$\bar x \pm s $ ）一般资料 观察组（n = 30） 对照组（n = 30） t/χ2 P 年龄（岁） 7.85±3.42 7.13±3.26 0.835 0.407 性别[n（%）] 男性 17（56.67） 13（43.33） 0.069 0.794 女性 18（60.00） 12（40.00） 抗体类型[n（%）] 抗NMDAR 24（80.00） 25（83.33） 0.104 0.845 抗LGI1 3（10.00） 2（6.67） 抗VGKC 3（10.00） 3（10.00） 
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表 2 2组疗效对比（n）
Table 2. Comparison of therapeutic effects between the two groups （n）
组别 显效 有效 无效 总有效率（%） 观察组（n = 30） 22 5 3 90.00 对照组（n = 30） 13 7 10 66.67 χ2 4.812 P 0.028* *P < 0.05。
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表 3 2组治疗前后T淋巴细胞亚群对比（
$\bar x \pm s $ ）Table 3. Comparison of T lymphocyte subsets between the two groups before and after treatment （
$\bar x \pm s $ ）项目 观察组（n = 30） 对照组（n = 30） 组间治疗后t值 P 治疗前 治疗后 治疗前 治疗后 CD3+ 59.37 ± 4.68 66.58 ± 4.57△# 59.73 ± 4.73 63.22 ± 4.42△ 2.895 0.005* CD4+ 37.69 ± 4.88 46.57 ± 5.24△# 36.83 ± 4.95 41.46 ± 4.87△ 3.913 < 0.001* CD8+ 26.34 ± 3.66 21.46 ± 2.11△# 26.75 ± 3.78 23.67 ± 2.85△ 3.414 0.001* CD4+/CD8+ 1.40 ± 0.28 1.95 ± 0.43△# 1.39 ± 0.22 1.65 ± 0.36△ 2.930 0.005* △组内比；#组间比；*P < 0.05。
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表 4 2组治疗前后PD-1、PD-L1水平对比（
$\bar x \pm s $ ）Table 4. Comparison of PD-1 and PD-L1 levels between the two groups before and after treatment （
$\bar x \pm s $ ）项目 观察组（n = 30） 对照组（n = 30） 组间治疗后t值 P 治疗前 治疗后 治疗前 治疗后 PD-1/CD4+ 15.27 ± 2.58 19.55 ± 2.76△# 15.38 ± 2.63 17.68 ± 2.61△ 2.696 0.009* PD-L1/CD4+ 20.14 ± 3.25 26.46 ± 2.54△# 21.47 ± 3.38 23.57 ± 2.63△ 4.329 < 0.001* PD-1/CD8+ 10.52 ± 1.77 14.38 ± 2.13△# 10.96 ± 1.65 12.15 ± 1.87△ 4.309 < 0.001* PD-L1/CD8+ 9.35 ± 1.35 15.36 ± 2.46△# 9.64 ± 1.45 13.29 ± 2.14△ 0.426 0.001* △组内比；#组间比；*P < 0.05。
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表 5 2组治疗前后免疫球蛋白水平对比（
$\bar x \pm s $ ）Table 5. Comparison of immunoglobulin levels between the two groups before and after treatment （
$\bar x \pm s $ ）项目 观察组（n = 30） 对照组（n = 30） 组间治疗后t值 P 治疗前 治疗后 治疗前 治疗后 IgA（g/L） 0.88 ± 0.22 0.43 ± 0.13△# 0.90 ± 0.25 0.67 ± 0.18△ 5.920 < 0.001* IgG（g/L） 8.53 ± 2.11 6.44 ± 1.51△# 8.62 ± 2.02 7.52 ± 1.88△ 2.453 0.017* IgM（g/L） 1.28 ± 0.33 0.92 ± 0.26△# 1.32 ± 0.35 1.14 ± 0.29△ 3.701 < 0.001* △组内比；#组间比；*P < 0.05。
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