慢性乙型肝炎患者外周血树突状细胞表面 HLA-Ⅱ分子表达模式研究

Expression patterns of HLA-Ⅱ on circulating mDC and pDC in patients with hepatitis B

目的观察经典HLA-Ⅱ分子(HLA-DR/DQ/DP)在慢性乙型肝炎(CHB)患者外周血树突状细胞表面的表达组合模式并探讨其临床意义。方法分离来自健康对照(HC)、慢性乙型肝炎轻中度(MCHB)、慢性乙型肝炎重度(SCHB)以及慢加急性肝衰竭(ACLF)患者的外周血单个核细胞(PBMC),采用流式细胞技术观察髓样树突状细胞(myeloid DC,mDCs)、浆样树突状细胞(plasmacytoid DC,pDCs)及表面HLA-DR/DQ/DP单阳、双阳及三阳性细胞比例,分析其与疾病严重程度之间的相关性。结果 mDC和pDC比例在HC组和MCHB组无明显差别(mDC:0.185%±0.191%vs 0.162%±0.175%,P=0.599;pDC:0.218%±0.246%vs 0.158%±0.154%,P=0.247),但SCHB组(mDC:0.079%±0.049%vs 0.185%±0.191%,P=0.023;pDC:0.095%±0.103%vs 0.218%±0.246%,P=0.027)及ACLF组(mDC:0.076%±0.052%vs 0.185%±0.191%,P=0.022;pDC:0.109%±0.082%vs 0.218%±0.246%,P=0.049)均明显低于HC组。健康对照和CHB患者mDC表面均呈现HLA-DR/DQ共同高表达、HLA-DP低表达的模式;pDC表面HLA-Ⅱ分子在HC组呈现HLA-DR/DQ共同高表达同时HLA-DP低表达模式及HLA-DR/DQ/DP共同低表达的模式,除此之外CHB患者还存在HLA-DR/DQ/DP共同低表达及HLA-DP高表达同时HLA-DR/DQ共同低表达的模式。结论与HC组相比,SCHB组及ACLF组患者的mDC与pDC的比例均明显下降。CHB患者mDC表面的HLA-Ⅱ分子表达模式与健康对照一致,而pDC表面的HLA-Ⅱ分子则呈现出多样化表达模式。差异的HLA-Ⅱ分子表达模式可能对HBV持续感染产生重要作用。

The genetic variants in the HLA- Ⅱ gene show the strongest genome-wide association with chronic hepatitis B virus （HBV） infection and persistence or recovery in Asians. However, the different expression patterns of HLA-DR/DQ/DP on cell surface had not been investigated for potential effects on HBV disease. Here we aim to analyze the expression patterns of these 3 HLA- Ⅱ proteins on circulating mDC and pDC in CHB patients and healthy controls, and analyze the clinical parameters in patients. Results showed that compared with healthy donors, the percentage of mDC and pDC were significantly decreased in severe chronic hepatitis B（SCHB） and acute-on- chronic liver failure （ACLF） patients （mDC： 0.079%±0.049% vs 0.185% ±0.191% , P=0.023; 0.076%±±0.052% vs 0.185%±0.191%, P=0.022. pDC： 0.095%±0.103% vs 0.218%_±0.246%, P--0.027; 0.109%±0.082% vs 0.218%± 0.246%, P=0.049）. mDe of both HC and CHB groups demonstrated high HLA-DR/DQ and low HLA-DP. While the patterns are variety on pDC： compared with healthy donors, there were other two different natterns： HLA-DR/DO/DP all high together and low expression of HLA-DR/ DQ with high HLA-DP. Our findings suggest that the percentage of mDC and pDC are decreased in CHB patients. The varied expression patterns of HLA-Ⅱ on pDC may play a significant role during the immune response to HBV.