雷公藤对慢性期艾滋病患者免疫重建和免疫激活的影响

发布时间：2018-07-18 21:19

【摘要】：背景与目的:在联合抗反转录病毒治疗(Combined antiretroviral therapy,cART)治疗下,绝大多数HIV感染者可以达到持续的病毒抑制,但是15-30%的HIV感染者在病毒长期完全抑制的情况下,CD4+T淋巴细胞数仍不能得到满意的恢复,这种现象称为免疫重建不全(Incomplete immune reconstitution),而免疫重建不全的感染者称为免疫无应答者(Immunenon-responders,INRs)和免疫部分应答者。免疫重建不全发生的重要机制之一是多种原因所致的免疫激活,而免疫激活又对HIV相关非AIDS并发症的发生以及HIV储存库的维持起到促进作用。本研究旨在探究雷公藤,一种临床上在多种自身免疫性疾病中广泛应用的免疫抑制剂,是否可以抑制慢性期艾滋病免疫重建不全患者的免疫激活,影响其病毒储存库,并通过与未经雷公藤治疗的免疫重建不良者进行对照,探究雷公藤能否对免疫重建不全者的CD4+T细胞计数和增长速率起到持续的改善作用。方法:从北京协和医院艾滋病诊疗中心选出18例符合免疫重建不全定义的HIV感染者,在cART基础上加用治疗量的雷公藤多甙片(20mgtid),持续1年,每3个月规律随访,1年后停止雷公藤治疗后每6个月随访,收集临床资料并留取外周血标本,测定外周血T淋巴细胞亚群,留取全血、血浆冻存,后续分别用来测量总HIV-DNA和血浆炎症因子水平。回顾性的从北京协和医院艾滋病诊疗中心的就诊患者中筛选符合免疫重建不全定义,且年龄与实验组匹配的患者作为对照组,对比实验组与对照组在雷公藤治疗相应cART治疗时间段内CD4+T细胞增长情况。结果:1、雷公藤对免疫重建不全者外周血CD4+T细胞计数的影响对于实验组患者,雷公藤联合cART治疗12月可使CD4+T细胞计数显著增长(由188±61/μl增至272±79/μl,p0.0001)。CD4+ T细胞计数增长以记忆CD4+ T细胞为主。实验组平均在cART治疗2.5年加用雷公藤治疗,雷公藤治疗期间CD4+T细胞计数增长速率较雷公藤治疗前增长速率增高(34.0 cells/mm3/年增至82.0 cells/mm3/年,p=0.077);实验组雷公藤停药后CD4+T细胞增长速率显著低于雷公藤治疗期间速率(82.0cells/mm3/年to23.5cells/mm3/年);非雷公藤组cART治疗0.5-3.5年间CD4+T细胞增长速率为27 cells/mm3/年,显著低于实验组雷公藤治疗期间CD4+T细胞增长速率(p=0.022)。2、雷公藤对实验组患者血浆炎症因子的影响对雷公藤治疗组患者开始加用雷公藤多甙治疗的1年前、雷公藤治疗基线(0年)、加用雷公藤0.5年、加用雷公藤1年,共4个随访点留取的血浆用液相芯片法对 13 种炎症因子进行测量。IP-10、MIP-1β、MCP-1、IFN-α2、IL-15、IL-12p40在加用雷公藤多甙治疗后较治疗前显著下降(至少在雷公藤治疗半年或治疗1年较雷公藤治疗0年有显著下降,p0.05)。IP-10与两种干扰素的相关性分析提示,IP-10浓度与IFNγ具有显著正相关性。3、雷公藤治疗组患者HIV储存库的变化情况雷公藤治疗前、治疗中、治疗后免疫重建不全患者HIV储存库的变化率无明显变化。结论:1、雷公藤多甙可显著提高HIV感染免疫重建不全患者外周血CD4+ T淋巴细胞计数和CD4+T细胞增长速度,以记忆CD4+T细胞的增长为主,但CD4+T细胞计数增长速度的提高在停药后不能持续。2、免疫重建不全的患者血浆 IP-10、MIP-1β、MCP-1、IFN-α2、IL-15、IL-12p40水平在加用雷公藤多甙治疗后较治疗前显著下降,以IP-10下降最为显著;IP-10浓度与IFNγ具有显著正相关性。3、雷公藤多甙联合cART治疗对于免疫重建不全患者的HIV储存库未发现有明显影响。
[Abstract]:Background and purpose: under the treatment of Combined antiretroviral therapy (cART), the overwhelming majority of HIV infected persons can achieve continuous viral inhibition, but the number of CD4+T lymphocytes in 15-30% HIV infected persons is still not satisfactory in the case of long-term complete inhibition of the virus. This phenomenon is called immunization. Incomplete immune reconstitution, and immune reconstructive infections are known as immune non responders (Immunenon-responders, INRs) and immune responses. One of the important mechanisms of immune reconstruction is a variety of causes of immune activation, and immune activation is also responsible for the occurrence of non AIDS complications related to HIV and the occurrence of HIV related complications. The purpose of this study is to explore the effect of the maintenance of the HIV repository. The purpose of this study is to explore the widely used immunosuppressants in many autoimmune diseases, which can inhibit the immune activation of patients with chronic AIDS immune reconstitution, affect their virus storage and through immune reconstruction with untreated Tripterygium wilfordii. To investigate whether Tripterygium wilfordii can continue to improve the CD4+T cell count and growth rate of immune reconstructive patients. Methods: 18 cases of HIV infected by immunoreconstruction were selected from the AIDS diagnosis and treatment center of Peking Union Medical College Hospital, and the dose of Tripterygium wilfordii (20mgtid) was added on the basis of cART. After 1 years, follow up every 3 months and 1 years after 1 years to stop the follow-up of Tripterygium wilfordii, collect the clinical data and leave the peripheral blood samples, determine the peripheral blood T lymphocyte subgroup, leave the whole blood, the plasma cryopreservation, then measure the total HIV-DNA and plasma inflammatory factors respectively. In the patients with heart disease, the patients who were matched with the experimental group were selected as the control group, and the CD4+T cell growth in the corresponding cART treatment period was compared between the experimental group and the control group. Results: 1, the effect of Tripterygium wilfordii on the peripheral blood CD4+T cell count in the patients with immune reconstitution insufficiency was in the experimental group. Patients, Tripterygium wilfordii combined with cART treatment in December can increase the number of CD4+T cells significantly (from 188 + 61/ Mu l to 272 + 79/ L, P0.0001).CD4+ T cell count increase to memory CD4+ T cells. The experimental group was treated with Tripterygium Wilfordii in 2.5 years of cART treatment, and the growth rate of cell count increased before Tripterygium wilfordii treatment. The rate increased (34 cells/mm3/ years to 82 cells/mm3/ years, p=0.077), and the rate of CD4+T cell growth after Tripterygium wilfordii was significantly lower than that of Tripterygium wilfordii (82.0cells/mm3/ year to23.5cells/mm3/). The CD4+T fine cell growth rate of non Tripterygium group cART treatment was 27 cells/mm3/ years, which was significantly lower than that of the experimental group. CD4+T cell growth rate (p=0.022).2 during the treatment of rattan, the effect of Tripterygium wilfordii on the plasma inflammatory factors of the patients in the experimental group was 1 years before the Tripterygium wilfordii treatment group was treated with Tripterygium wilfordii (0 years), 0.5 years with Tripterygium wilfordii, plus 1 years of Tripterygium wilfordii, and a total of 4 follow up points for plasma liquid chromatography 13 kinds of inflammatory factors were measured.IP-10, MIP-1 beta, MCP-1, IFN- alpha 2, IL-15, IL-12p40 were significantly lower than before treatment with Tripterygium wilfordii treatment (at least in the treatment of Tripterygium wilfordii for six months or 1 years compared with Tripterygium wilfordii treatment 0 years, P0.05).IP-10 and two kinds of interferon analysis suggested that IP-10 concentration and IFN gamma have significant With positive correlation.3 and the changes of HIV storage in Tripterygium wilfordii treatment group, before Tripterygium wilfordii treatment, there was no significant change in the change rate of HIV storage in patients with immune reconstruction after treatment. Conclusion: 1, Tripterygium wilfordii can significantly increase the number of CD4+ T lymphocyte counts and CD4+T cell growth rate in peripheral blood of patients with HIV infection. The growth of CD4+T cells was mainly in memory, but the increase in the growth rate of CD4+T cell counts was not sustained after the withdrawal of.2. The plasma IP-10, MIP-1 beta, MCP-1, IFN- alpha 2, IL-15, and IL-12p40 were significantly decreased after the treatment with Tripterygium wilfordii, and the most significant decreased with IP-10. IP-10 concentration and IFN gamma were the most significant. There was a significant positive correlation between.3. Tripterygium glycosides combined with cART treatment had no significant effect on HIV storage in patients with incomplete immune reconstitution.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R512.91

【相似文献】