目的 探討阿法骨化醇聯(lián)合小劑量利妥昔單抗治療成人持續(xù)性原發(fā)免疫性血小板減少癥（ITP）的臨床療效以及其對(duì)患者外周血樹突狀細(xì)胞（DC）亞群和血清輔助性T細(xì)胞（Th）1/Th2相關(guān)細(xì)胞因子、白細(xì)胞介素（IL）-17、1，25-雙羥維生素D₃［1，25（OH）₂D₃］水平的影響。方法 回顧性選擇北京航天總醫(yī)院2019年1月—2021年12月收治的92例成人持續(xù)性ITP患者為研究對(duì)象，根據(jù)治療方法的不同分成試驗(yàn)組46例與對(duì)照組46例。對(duì)照組給予小劑量利妥昔單抗注射液靜脈輸注治療，每次100 mg，每次30 min，每周1次，共4次。試驗(yàn)組在對(duì)照組基礎(chǔ)上聯(lián)合給予阿法骨化醇膠囊口服治療，每次1粒，每天1次。兩組均連續(xù)治療4周。比較兩組臨床療效。分別于治療前后檢測(cè)兩組患者外周血DC亞群［漿細(xì)胞樣樹突狀細(xì)胞（pDC）、髓樣樹突狀細(xì)胞（mDC）］，血清Th1/Th2相關(guān)細(xì)胞因子［IL-2、γ干擾素（IFN-γ）、IL-4、IL-10］，血清IL-17、1，25（OH）₂D₃水平。統(tǒng)計(jì)兩組不良反應(yīng)發(fā)生情況。結(jié)果 試驗(yàn)組總有效率為82.61%，與對(duì)照組的63.04%相比顯著升高（P<0.05）。兩組治療后外周血mDC占比均較本組治療前顯著降低（P<0.05），外周血pDC占比均較本組治療前顯著升高（P<0.05）；且均以試驗(yàn)組的改善更顯著（P<0.05）。兩組治療后血清IL-2、IFN-γ水平均較本組治療前顯著降低（P<0.05），血清IL-4、IL-10水平均較本組治療前顯著升高（P<0.05）；且治療后，試驗(yàn)組血清IL-2、IFN-γ水平均顯著低于對(duì)照組（P<0.05），血清IL-4、IL-10水平均顯著高于對(duì)照組（P<0.05）。兩組治療后血清IL-17水平均較本組治療前顯著降低（P<0.05），血清1，25（OH）₂D₃水平均較本組治療前顯著升高（P<0.05）；且治療后，試驗(yàn)組血清IL-17水平顯著低于對(duì)照組（P<0.05），血清1，25（OH）₂D₃水平顯著高于對(duì)照組（P<0.05）。試驗(yàn)組不良反應(yīng)總發(fā)生率（19.57%）與對(duì)照組（17.39%）比較，差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）。結(jié)論 阿法骨化醇聯(lián)合小劑量利妥昔單抗治療成人持續(xù)性ITP能有效調(diào)節(jié)患者外周血DC亞群和血清Th1/Th2細(xì)胞因子、IL-17、1，25（OH）₂D₃水平，提高臨床療效，且安全性較好。

Objective To investigate the clinical efficacy of alfacalcitol combined with low-dose rituximab in treatment of persistent primary immune thrombocytopenia (ITP) in adults and its effects on peripheral blood dendritic cell (DC) subsets and serum helper T cell (Th) 1/Th2cytokines, interleukin (IL-17) and 1, 25-dihydroxyvitamin D₃[1, 25(OH)₂D₃] levels. Methods A total of 92 adult patients with persistent ITP admitted to Beijing Aerospace General Hospital from January 2019 to December 2021 were selected as the study subjects, and they were divided into experimental group (n=46) and control group (n=46) according to the different treatment methods. Patients in the control group were treated with intravenous infusion of low dose of Rituximab Injection, 100 mg each time, and infusion for 30 min each time, once a week, four times in total. On the basis of the control group, patients in the experimental group were given Alfacalciferol Capsules orally, one capsule each time, once a day. Patients in both groups were treated continuously for four weeks. The clinical theraputic efficacy of the two groups was compared after treatment. Peripheral blood DC subsets[plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC)], serum Th1/Th2 cytokines[IL-2, γ -interferon (IFN- γ), IL-4, IL-10] and serum IL-17, 1, 25(OH)₂D₃ were detected before and after treatment. The adverse reactions of the two groups were recorded. Results The total effective rate of experimental group was 82.61%, significantly higher than that of control group (63.04%, P<0.05). After treatment, the percentage of mDC in peripheral blood of two groups were significantly decreased (P<0.05), and the percentage of pDC in peripheral blood was significantly increased (P<0.05). The improvement in experimental group was more significant (P<0.05). After treatment, the levels of serum IL-2 and IFN- γ in two groups were significantly decreased compared with before treatment (P<0.05), and the concentrations of serum IL-4 and IL-10 in two groups were significantly increased compared with before treatment (P<0.05). After treatment, the levels of serum IL-2 and IFN- γ in experimental group were significantly lower than those in control group (P<0.05), and the contents of serum IL-4 and IL-10 in experimental group were significantly higher than those in control group (P<0.05). After treatment, the serum IL-17 level in two groups were significantly decreased (P<0.05), and the serum 1, 25(OH)₂D₃ content in two groups were significantly increased (P<0.05). After treatment, serum IL-17 level in experimental group was significantly lower than that in control group (P<0.05), and serum 1, 25(OH)₂D₃ concentration in experimental group was significantly higher than that in control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the experimental group (19.57%) and the control group(17.39%, P>0.05). Conclusion Alfacalccitol combined with low-dose rituximab can effectively regulate peripheral blood DC subsets and serum Th1/Th2 cytokines, IL-17, 1, 25(OH)₂D₃ levels in treatment of adult persistent ITP, and improve clinical efficacy with good safety.

R973

航天醫(yī)科醫(yī)療項(xiàng)目（2020YK23）