不同免疫状态下慢性HBV感染者外周血调节性B细胞及血清IL-10和IP-10的表达特点

Characteristics of regulatory B cells and serum IL-10, IP-10 in different immune phases of chronic hepatitis B virus infection

目的观察不同免疫状态下慢性乙型肝炎病毒(HBV)感染者外周血调节性B细胞(Breg细胞)比例及血清白细胞介素-10(IL-10)和干扰素诱导蛋白-10(IP-10)水平特点。方法采集63例不同免疫状态下慢性HBV感染者和16例健康个体的外周血,采用流式细胞术检测其外周血Breg细胞(CD24hiCD38hi B细胞)比例,采用Luminex技术检测其血清IL-10和IP-10水平。结果免疫活化组外周血Breg细胞比例高于免疫耐受组和健康对照组[(7.89±3.37)%vs(4.77±2.42)%,F=9.27,P=0.010;(7.89±3.37)%vs(3.83±2.14)%,F=16.55,P<0.001],免疫耐受组成熟B细胞(CD24intCD38int B细胞)比例低于健康对照组[(43.40±10.74)%vs(54.56±10.72)%,F=7.39,P=0.02]。免疫活化组血清IL-10和IP-10水平高于免疫耐受组、非活动HBV携带组及健康对照组[(22.53±24.81)pg/ml vs(0.69±1.34)pg/ml,(22.53±24.81)pg/ml vs(0.31±1.12)pg/ml,(22.53±24.81)pg/ml vs(0.003±0.009)pg/ml,P均<0.001;(2 540.19±1 870.73)pg/ml vs(720.52±285.73)pg/ml,(2 540.19±1 870.73)pg/ml vs(567.38±208.72)pg/ml,(2 540.19±1 870.73)pg/ml vs(624.80±274.45)pg/ml,P均<0.001]。慢性HBV感染者外周血Breg细胞比例与血清IL-10水平、ALT水平呈正相关关系(r=0.282,P=0.025;r=0.305,P=0.026),免疫活化期感染者血清IL-10、IP-10水平与ALT水平呈正相关(r=0.715,P<0.001;r=0.653,P<0.001)。结论免疫活化期的慢性HBV感染者Breg细胞比例升高,且其外周血IL-10、IP-10也显著升高。慢性HBV感染者外周血Breg细胞比例与血清IL-10、ALT水平正相关,免疫活化期感染者血清IL-10、IP-10水平与ALT水平正相关。

Objective To investigate the frequencies of regulatory B cells （Bregs） in the peripheral blood and the levels of serum interleukin-10 （IL-10） and interferon-γ-induced protein 10 （IP-10） in different immune phases of chronic hepatitis B virus （HBV） infection. Methods Total of sixty-three patients with chronic HBV infection, while 16 healthy controls were enrolled. The frequencies of Bregs （CD24hiCD38hi B cells） in the peripheral blood were measured by lfow cytometry. IL-10 and IP-10 levels were determined with the Human Magnetic Cytokine/Chemokine Bead Panel on the MAGPIX instrument. Results Compared to immune tolerant phase （IT） and healthy controls （HC）, the frequencies of Bregs were signiifcantly elevated in the immune reactive phase （IA） [ （7.89 ± 3.37）%vs （4.77 ± 2.42%）, F=9.27, P=0.010;（7.89 ± 3.37）%vs （3.83 ± 2.14）%, F=16.55, P〈0.001 ]. The frequencies of mature B cells （CD24intCD38int B cells） were signiifcantly, P=0.02]. Serum IL-10 and IP-10 levels were also elevated signiifcantly in IA group as compared with IT, inactive HBV carrier state （IC） and HC group [（22.53 ± 24.81） pg/ml vs （0.69 ± 1.34） pg/ml, （22.53 ± 24.81） pg/ml vs （0.31 ± 1.12） pg/ml, （22.53 ± 24.81） pg/ml vs （0.003 ± 0.009） pg/ml, P all 〈 0.001;（2 540.19 ± 1 870.73） pg/ml vs （720.52 ± 285.73） pg/ml, （2 540.19 ± 1 870.73） pg/ml vs （567.38 ± 208.72） pg/ml, （2 540.19 ± 1 870.73） pg/ml vs （624.80 ± 274.45） pg/ml, P all〈0.001]. The frequencies of Bregs positively correlated with IL-10 and ALT levels （r = 0.282, P = 0.025; r = 0.305, P = 0.026） in chronic HBV infection. In addition, IL-10 and IP-10 levels were also positively correlated with ALT levels （r = 0.715, P 〈 0.001; r = 0.653, P 〈 0.001） in immune reactive phase （IA）. Conclusions The frequencies of Bregs, IL-10 and IP-10 levels were elevated significantly in immune reactive phase （IA） of chronic HBV infection. The frequencies of Bregs positively correlated with IL-10 and ALT levels in chronic HBV infection. IL-10 and IP-10 levels were also positively correlated with ALT levels in immune reactive phase （IA） of chronic HBV infection.