大剂量地塞米松对成人原发免疫性血小板减少症患者外周血调节性T细胞的影响及其临床疗效

Effect of high-dose dexamethasone on peripheral blood regulatory T cells in adult patients with primary immune thrombocytopenia and its clinical efficacy

目的探讨大剂量地塞米松对成人原发免疫性血小板减少症(ITP)患者调节性T细胞(Treg)的影响及其临床疗效。方法选择2020年7月至2021年12月新乡医学院第一附属医院收治的120例ITP患者为研究对象。根据治疗方法将患者分为对照组和观察组,每组60例。对照组患者给予醋酸泼尼松片,每日l.0~1.5 mg·kg^(-1),分3次口服,连续服用3周;观察组患者给予醋酸地塞米松片口服,每次20 mg,每日早晚各1次,持续服用4 d,然后停药1周,再重复1个疗程,共治疗2个疗程。对照组中8例因疗效欠佳、症状恶化等原因退出,观察组中4例因疗效欠佳等原因退出。分别于治疗1周时、治疗结束时、治疗后2周,根据患者的血小板和临床表现评估临床疗效,依据临床疗效将患者分为完全缓解组、显效组和无效组;分别于治疗后1、2个月,根据患者的血小板和临床表现评估复发情况;分别于治疗前后采集2组患者晨起空腹静脉血3~5 mL,使用流式细胞仪检测ITP患者外周血CD4^(+)CD25^(+)Treg细胞亚群水平;采用受试者操作特征(ROC)曲线评估CD4^(+)CD25^(+)Treg细胞亚群水平对成人ITP患者预后的预测价值。结果治疗1周时、治疗结束时及治疗后2周,对照组患者的有效率分别为40.4%(21/52)、55.8%(29/52)、71.2%(37/52),观察组患者的有效率分别为60.7%(34/56)、76.8%(43/56)、82.1%(46/56);治疗1周时及治疗结束时,观察组患者的有效率显著高于对照组(χ^(2)=4.459、5.359,P<0.05);治疗后2周,观察组与对照组患者的有效率比较差异无统计学意义(χ^(2)=1.830,P>0.05)。治疗后1、2个月时,对照组患者的复发率分别为26.9%(14/52)、48.1%(25/52),观察组患者的复发率分别为16.1%(9/56)、21.4%(12/56);治疗后1个月时,观察组与对照组患者的复发率比较差异无统计学意义(χ^(2)=1.894,P>0.05);治疗后2个月时,观察组患者的复发率显著低于对照组(χ^(2)=8.502,P<0.05)。治疗前,观察组与对照组患者的外周血CD4^(+)CD25^(+)Treg水平比较差异无统计学意义(P>0.05);治疗结束时,2组患者的CD4^(+)CD25^(+)Treg水平显著高于治疗前,观察组患者的CD4^(+)CD25^(+)Treg水平显著高于对照组(P<0.05)。完全缓解组和显效组患者外周血CD4^(+)CD25^(+)Treg水平显著高于无效组,完全缓解组患者的外周血CD4^(+)CD25^(+)Treg水平显著高于显效组(P<0.05)。Pearson相关性分析结果显示,外周血CD4^(+)CD25^(+)Treg水平与临床疗效呈正相关(r=0.562,P<0.05),与病程呈负相关(r=-0.379,P<0.05)。ROC曲线分析显示,外周血CD4^(+)CD25^(+)Treg水平预测成人ITP预后的曲线下面积为0.801(95%置信区间为0.699~0.903,P<0.05);以3.416%为截断值时,CD4^(+)CD25^(+)Treg预测成人ITP预后的敏感度为0.840,特异度为0.759,约登指数为0.599。对照组和观察组患者的不良反应发生率分别为51.9%(21/52)、19.6%(11/56);观察组患者的不良反应发生率显著低于对照组(χ^(2)=12.320,P<0.05)。结论大剂量地塞米松冲击治疗可有效改善成人ITP临床症状,其作用机制可能与提高CD4^(+)CD25^(+)Treg水平、增加免疫力有关;且CD4^(+)CD25^(+)Treg可作为预测成人ITP预后的有效指标。

Objective To investigate the effect of high-dose dexamethasone on regulatory T cells(Treg)in adult patients with primary immune thrombocytopenia(ITP)and its clinical efficacy.Methods One hundred and twenty patients with ITP admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2020 to December 2021 were selected as study subjects.According to the treatment method,the patients were divided into the control group and the observation group,with 60 cases in each group.The patients in the control group were given prednisone acetate tablets at a daily dose of 1.0-1.5 mg·kg^(-1)in 3 oral doses for 3 weeks;the patients in the observation group were given dexamethasone acetate tablets orally at 20 mg once in the morning and once in the evening for 4 days,then treatment was stopped for 1 week,and the treatment was repeated for 1 course of treatment,the treatment was performed for a total of 2 courses.In the control group,8 patients withdrew due to poor efficacy and worsening symptoms;4 patients in the observation group withdrew due to poor efficacy and other reasons.The clinical efficacy was evaluated according to the patients′platelets and clinical performance at 1 week of treatment,the end of treatment,2 weeks after treatment,respectively;and the patients were divided into complete remission group,apparent effect group and ineffective group according to clinical efficacy;at 1 and 2 months after treatment,the recurrence was evaluated based on the patient′s platelets and clinical manifestations.Before and after treatment,3-5 mL of fasting venous blood was collected from of patients in the morning in the two groups,the levels of CD4^(+)CD25^(+)Treg cell subpopulations in peripheral blood of ITP patients was detected by flow cytometry.The predictive value of CD4^(+)CD25^(+)Treg cell subpopulations levels on the prognosis of adult ITP patients was evaluated by receiver operating characteristic(ROC)curves.Results At 1 week of treatment,the end of treatment and 2 weeks after treatment,the effective rates of patients in the control group were 40.4%(21/52),55.8%(29/52)and 71.2%(37/52),respectively;and the effective rates of patients in the observation group were 60.7%(34/56),76.8%(43/56)and 82.1%(46/56),respectively;at 1 week of treatment and the end of treatment,the effective rate of patients in the observation group was significantly higher than that in the control group(χ^(2)=4.459,5.359;P<0.05);at 2 weeks after treatment,there was no statistically significant difference in the effective rates of patients between the observation group and the control group(χ^(2)=1.830,P>0.05).At 1 and 2 months after treatment,the recurrence rates of patients in the control group were 26.9%(14/52)and 48.1%(25/52),respectively;and the recurrence rates of patients in the observation group were 16.1%(9/56)and 21.4%(12/56),respectively;at 1 month after treatment,there was no statistically significant difference in the recurrence rates of patients between the observation group and the control group(χ^(2)=1.894,P>0.05);at 2 months after treatment,the recurrence rate of patients in the observation group was significantly lower than that in the control group(χ^(2)=8.502,P<0.05).Before treatment,there was no statistically significant difference in the peripheral blood CD4^(+)CD25^(+)Treg level of patients between the observation group and the control group(P>0.05);at the end of treatment,the peripheral blood CD4^(+)CD25^(+)Treg level of patients was significantly higher than that before treatment in the two groups,and the peripheral blood CD4^(+)CD25^(+)Treg level of patients in the observation group was significantly higher than that in the control group(P<0.05).The peripheral blood CD4^(+)CD25^(+)Treg levels of patients in the complete remission group and the apparent effect group were significantly higher than those in the ineffective group,while the peripheral blood CD4^(+)CD25^(+)Treg level of patients in the complete remission group was significantly higher than that in the apparent effect group(P<0.05).Pearson correlation analysis showed that CD4^(+)CD25^(+)Treg level was positively correlated with clinical efficacy(r=0.562,P<0.05),and it was negatively correlated with course of disease.ROC curve analysis showed that area under the curve of peripheral blood CD4^(+)CD25^(+)Treg level in predicting prognosis of the adult ITP was 0.801(95%confidence interval 0.699-0.903,P<0.05);when the cut-off value of peripheral blood CD4^(+)CD25^(+)Treg level was 3.416%,the sensitivity of peripheral blood CD4^(+)CD25^(+)Treg level in predicting the prognosis of adult with ITP was 0.840.The incidence of adverse reactions of patients in the control group and observation group was 51.9%(21/52)and 19.6%(11/56),respectively;the incidence of adverse reactions of patients in the observation group was significantly lower than that in the control group(χ^(2)=12.320,P<0.05).Conclusion High-dose dexamethasone pulse therapy can effectively improve the clinical symptoms of adult with ITP,and its mechanism of action may be related to increasing CD4^(+)CD25^(+)Treg levels and enhancing immunity;and CD4^(+)CD25^(+)Treg can serve as an effective indicator for predicting the prognosis of adult with ITP.