慢性乙型肝炎干扰素治疗前后树突状细胞的变化及其与疗效相关性研究

Involvement of dendritic cells frequency and function in outcomes of interferon-α therapy for chronic hepatitis B patients

目的探讨慢乙肝干扰素α（IFNα）治疗前后髓样树突状细胞（mDC）和浆样树突状细胞（pDC）的变化及其与病毒学、生化学指标的关系。方法采集30例HBeAg阳性慢乙肝患者IFNα治疗前和治疗12周时的外周血，用流式细胞仪检测mDC和pDC的频数及CD86表达水平。根据IFNα治疗后生化学指标和病毒学指标变化，把患者分为ALT复常组、ALT未复常组及病毒学应答组、病毒学无应答组，分析IFNα治疗前后不同组DC变化。结果（1）IFNα治疗12周时ALT复常组pDC频率（0．25％±0．14％）较基线（0．18％±0．09％）升高（P=0．023），ALT未复常组mDC频率（0．58％±0．34％）及表面CD86阳性率（61．80％±22．52％）则较基线（分别为0．88％±0．51％，79．92％±25．94％）下降（P=0．025；P=0．036）。（2）IFNα治疗12周时病毒学应答组pDC表面CD86阳性率（46．86±12．22％）较基线（29．42±15．16％）升高（P=0．002），病毒学无应答组的mDC频率（0．51％±0．22％）及表面CD86阳性率（59．63％±22．94％）则较基线（分别为0．94％±0．58％，80．11％±29．34％）下降（P=0．006；P=0．049）。结论慢乙肝干扰素α治疗后，生化和病毒应答与pDC频率和功能增强相关，而mDC频率及功能的降低与IFN治疗后无生化和病毒应答相关。

Objective To elucidate the change in frequencies and functions of myeloid dendritic cell （mDC） and plasmacytoid dendritic cell （pDC） before and after interferon-α therapy for chronic hepatitis B （CHB） patients, and its correlation with virological and biochemical data. Methods Thirty patients with HBeAg-positive CHB who underwent IFN-α therapy were examined. Frequencies and expression of CD86 of mDC and pDC of peripheral blood were measured at baseline and treatment week （TW） 12 by flow eytometry. According to biochemical and virological parameters, the 30 patients were divided into ALT normalized group, ALT non-normalized group and virological responder group, virological non-responder group respectively. Statistical analysis of DC changes among different groups at baseline and TW12 was proceeded. Results （1） In the ALT normalized group, the pDC frequency at TW12 （0. 25 ± 0.14% ） was higher than that at baseline （0.18 ±0. 09% ） （P =0. 023） ; in the ALT non-normalized group, the mDC frequency （0.58 ± 0.34% ） and its surface CD86 expression （61.80 ± 22.52% ） decreased significantly as compared with baseline （0.88 ± 0. 51% ,79.92 ±25.94% , respectively） , （ P = 0. 025, P = 0. 036, respectively）. （2） In the virological responder group, the CD86 expression on pDC at TW12 （46.86 ± 12.22% ） was higher than that at baseline （ 29.42± 15.16% ） （ P = 0. 002） ; in the virological non-responder group, the mDC frequency （0.51 ± 0.22% ） and its surface CD86 expression （59.63± 22.94%） decreased significantly as compared with baseline （0.94 ± 0.58%, 80.11± 29.34%,respectively）, （P = 0. 006; P = 0. 049, respectively）. Conclusion In IFN-α therapy for CHB patients, the increments of pDC frequency and function were related to biochemical and viral response, and decreases of mDC frequency and function were related to non-biochemical and non-viral response.