中华实验和临床感染病杂志(电子版)
中華實驗和臨床感染病雜誌(電子版)
중화실험화림상감염병잡지(전자판)
CHINESE JOURNAL OF EXPERIMENTAL AND CLINICAL INFECTIOUS DISEASES(ELECTRONIC VERSION)
2014年
2期
191-197
,共7页
杨晨辰%黄睿%刘勇%严晓敏%武抗抗%曹淑凤%唐勤%孙静%吴超
楊晨辰%黃睿%劉勇%嚴曉敏%武抗抗%曹淑鳳%唐勤%孫靜%吳超
양신신%황예%류용%엄효민%무항항%조숙봉%당근%손정%오초
肝炎病毒,乙型%CD4+T细胞%CD8+T细胞%细胞因子%核苷(酸)类似物
肝炎病毒,乙型%CD4+T細胞%CD8+T細胞%細胞因子%覈苷(痠)類似物
간염병독,을형%CD4+T세포%CD8+T세포%세포인자%핵감(산)유사물
Hepatitis B virus%CD4+T cell%CD8+T cell%Cytokines%Nucleos(t)ide analogues
目的:观察不同免疫状态的慢性乙型肝炎病毒(HBV)感染者及抗病毒治疗后外周血CD4+T、CD8+T细胞比例、CD4+/CD8+比值及血清中细胞因子IL-6、IL-10、TNF-α和IFN-γ水平的变化特点及与HBeAg血清学转换的相关性。方法纳入79例处于不同免疫状态的慢性HBV感染者(其中非活动性HBV携带期15例、免疫耐受期20例、免疫活化期44例)及21例健康对照者为研究对象,采用流式细胞术检测其外周血CD4+T、CD8+T细胞比例。对其中33例免疫活化期患者进行核苷(酸)类似物抗病毒治疗并随访至48周。分别于治疗前(T0期)及治疗后4周(T1期)、8周(T2期)、12周(T3期)、24周(T4期)和48周(T5期)采集外周血,流式细胞术检测各时间点患者外周血CD4+T、CD8+T细胞比例。同时对部分患者血清标本中的细胞因子水平进行检测。结果在慢性HBV感染者中,免疫活化组患者外周血CD4+T细胞比例及CD4+/CD8+比值显著低于健康对照组(P均<0.05),而CD8+T细胞比例显著高于健康对照组(F =3.610,P <0.05)。抗病毒治疗后,△T0~T1、△T0~T2期,HBeAg血清学转换组外周血CD8+T细胞比例升高率显著高于未转换组(P均<0.05);△T0~T5期,HBeAg血清学转换组外周血CD4+T细胞比例升高率显著高于未转换组(Z =-2.200,P <0.05)。免疫活化组患者血清IL-10、IFN-γ水平均显著高于对照组和免疫耐受组(P均<0.05)。免疫活化组患者抗病毒治疗后12周及24周,血清IL-10水平显著下降(t=3.037、3.180,P均<0.05),与ALT水平、HBV DNA载量呈正相关关系(P均<0.05)。结论慢性HBV感染者在不同免疫状态下外周血T细胞亚群比例及血清细胞因子水平表现不同,免疫活化期患者与健康对照者比CD4+T比例及CD4+/CD8+下降,CD8+T比例升高,血清IL-10水平显著升高。HBeAg阳性患者,核苷(酸)类似物抗病毒治疗过程中外周血CD8+T细胞和CD4+T细胞的比例升高可能有助于预测HBeAg的血清学转换。
目的:觀察不同免疫狀態的慢性乙型肝炎病毒(HBV)感染者及抗病毒治療後外週血CD4+T、CD8+T細胞比例、CD4+/CD8+比值及血清中細胞因子IL-6、IL-10、TNF-α和IFN-γ水平的變化特點及與HBeAg血清學轉換的相關性。方法納入79例處于不同免疫狀態的慢性HBV感染者(其中非活動性HBV攜帶期15例、免疫耐受期20例、免疫活化期44例)及21例健康對照者為研究對象,採用流式細胞術檢測其外週血CD4+T、CD8+T細胞比例。對其中33例免疫活化期患者進行覈苷(痠)類似物抗病毒治療併隨訪至48週。分彆于治療前(T0期)及治療後4週(T1期)、8週(T2期)、12週(T3期)、24週(T4期)和48週(T5期)採集外週血,流式細胞術檢測各時間點患者外週血CD4+T、CD8+T細胞比例。同時對部分患者血清標本中的細胞因子水平進行檢測。結果在慢性HBV感染者中,免疫活化組患者外週血CD4+T細胞比例及CD4+/CD8+比值顯著低于健康對照組(P均<0.05),而CD8+T細胞比例顯著高于健康對照組(F =3.610,P <0.05)。抗病毒治療後,△T0~T1、△T0~T2期,HBeAg血清學轉換組外週血CD8+T細胞比例升高率顯著高于未轉換組(P均<0.05);△T0~T5期,HBeAg血清學轉換組外週血CD4+T細胞比例升高率顯著高于未轉換組(Z =-2.200,P <0.05)。免疫活化組患者血清IL-10、IFN-γ水平均顯著高于對照組和免疫耐受組(P均<0.05)。免疫活化組患者抗病毒治療後12週及24週,血清IL-10水平顯著下降(t=3.037、3.180,P均<0.05),與ALT水平、HBV DNA載量呈正相關關繫(P均<0.05)。結論慢性HBV感染者在不同免疫狀態下外週血T細胞亞群比例及血清細胞因子水平錶現不同,免疫活化期患者與健康對照者比CD4+T比例及CD4+/CD8+下降,CD8+T比例升高,血清IL-10水平顯著升高。HBeAg暘性患者,覈苷(痠)類似物抗病毒治療過程中外週血CD8+T細胞和CD4+T細胞的比例升高可能有助于預測HBeAg的血清學轉換。
목적:관찰불동면역상태적만성을형간염병독(HBV)감염자급항병독치료후외주혈CD4+T、CD8+T세포비례、CD4+/CD8+비치급혈청중세포인자IL-6、IL-10、TNF-α화IFN-γ수평적변화특점급여HBeAg혈청학전환적상관성。방법납입79례처우불동면역상태적만성HBV감염자(기중비활동성HBV휴대기15례、면역내수기20례、면역활화기44례)급21례건강대조자위연구대상,채용류식세포술검측기외주혈CD4+T、CD8+T세포비례。대기중33례면역활화기환자진행핵감(산)유사물항병독치료병수방지48주。분별우치료전(T0기)급치료후4주(T1기)、8주(T2기)、12주(T3기)、24주(T4기)화48주(T5기)채집외주혈,류식세포술검측각시간점환자외주혈CD4+T、CD8+T세포비례。동시대부분환자혈청표본중적세포인자수평진행검측。결과재만성HBV감염자중,면역활화조환자외주혈CD4+T세포비례급CD4+/CD8+비치현저저우건강대조조(P균<0.05),이CD8+T세포비례현저고우건강대조조(F =3.610,P <0.05)。항병독치료후,△T0~T1、△T0~T2기,HBeAg혈청학전환조외주혈CD8+T세포비례승고솔현저고우미전환조(P균<0.05);△T0~T5기,HBeAg혈청학전환조외주혈CD4+T세포비례승고솔현저고우미전환조(Z =-2.200,P <0.05)。면역활화조환자혈청IL-10、IFN-γ수평균현저고우대조조화면역내수조(P균<0.05)。면역활화조환자항병독치료후12주급24주,혈청IL-10수평현저하강(t=3.037、3.180,P균<0.05),여ALT수평、HBV DNA재량정정상관관계(P균<0.05)。결론만성HBV감염자재불동면역상태하외주혈T세포아군비례급혈청세포인자수평표현불동,면역활화기환자여건강대조자비CD4+T비례급CD4+/CD8+하강,CD8+T비례승고,혈청IL-10수평현저승고。HBeAg양성환자,핵감(산)유사물항병독치료과정중외주혈CD8+T세포화CD4+T세포적비례승고가능유조우예측HBeAg적혈청학전환。
Objective To investigate the percentages of CD4+T and CD8+T cells in the peripheral blood and serum cytokine levels (IL-6, IL-10, IFN-γand TNF-α) in patients with chronic hepatitis B virus (HBV) infection during different immune status and explore the association between the percentages of T cell subsets and HBeAg seroconversion. Methods Seventy-nine patients with chronic HBV infection as well as 21 healthy donors were enrolled in this study. Blood samples were collected for detecting the percentages of CD4+T and CD8+T cells by lfow cytometry. Thirty-three HBeAg positive CHB patients received antiviral treatment were successfully followed for 48 weeks. At the end of 48 weeks, 7 of 33 HBeAg positive CHB paitents achieved HBeAg seroconversion. The percentages of CD4+T and CD8+T cells were detected at ifve time points of antivirus treatment:T1 (4 week), T2 (8 week), T3 (12 week), T4 (24 week) and T5 (48 week). Serum cytokine levels were also detected by cytometric bead array (CBA). Results As compared with normal controls, the percentage of CD4+T cell and the ratio of CD4+/CD8+were lower in patients in the immune reactive phase (P all<0.05). However, the percentage of CD8+T cell was higher than normal controls (F=3.610, P<0.05). During the same monitoring period, the HBV DNA loads and ALT levels in patients who achieved HBeAg seroconversion decreased signiifcantly compared with patients without HBeAg seroconversion. Besides, the increase of CD8+T cells duing the periodΔT0-T1 andΔT0-T2 and the increase of CD4+T cells during periodΔT0-T5 were signiifcantly different between HBeAg seroconversion patients and HBeAg non-seroconversion patients (Z=-2.200, P<0.05). The cytokine levels of IL-10 and IFN-γin patients of immune reactive phase were higher than health controls and patients in immune tolerant phase (P all<0.05). The cytokine levels of IL-10 decreased signiifcantly at 12 weeks (T3) and 24 weeks (T4) of antiviral treatment (t=3.037 and 3.180, P all<0.05) and were positively correlated with the HBV DNA loads and ALT levels. Conclusions The percentages of CD4+T and CD8+T cell and serum cytokine levels were changed in different immune status of chronic HBV infection. The increase of CD8+T cell and CD4+T cell percentage during the process of antiviral treatment with HBeAg positive CHB patients were associated with high HBeAg seroconversion rate.