合并乙肝病毒感染对弥漫大B细胞淋巴瘤患者细胞免疫功能的影响

The impact of hepatitis B virus concurrent infection on peripheral T cells in diffuse large B cell lymphoma patients

背景与目的：乙型肝炎病毒（hepatitis virus B,HBV）感染与弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）密切相关,前期研究发现在接受联合免疫化疗的DLBCL患者中,HBsAg阳性者生存较差,但具体机制有待进一步证实。本研究通过分析HBV感染对DLBCL患者细胞免疫的影响,为阐明这一机制寻找细胞免疫方面的证据。方法：2004年3月—2013年6月共294例住院初治的DLBCL患者纳入本研究。采用四色流式分析患者外周血CD3＋、CD4＋、CD8＋细胞计数及CD4＋/CD8＋细胞比例,比较HBsAg阳性及阴性的DLBCL患者发病时、化疗后2～4个月、化疗后4～6个月及化疗后6～12个月上述参数的时序改变及2组间的差异。结果：与HBsAg阴性患者相比,HBsAg阳性DLBCL患者化疗前各淋巴细胞亚群差异无统计学意义（P〉0.05）;外周血CD4＋细胞计数在化疗后2～4个月显著低于HBsAg阴性患者;HBsAg阳性患者CD4＋/CD8＋比例降低,在化疗后4～12个月显著低于HBsAg阴性患者。结论：合并HBV感染对DLBCL患者化疗前细胞免疫状态无明显影响;HBsAg阳性的DLBCL患者化疗后出现更为明显和持续的细胞免疫抑制。

Background and purpose： The clinical relevance of HBV infection with respect to diffuse large B cell lymphoma（DLBCL） patients and immune patterns of T lymphocyte subsets during chemotherapy remains unclear. This study aimed to identify the characteristics of T-cell mediated immunity in DLBCL patients with HBV infection, thereafter, to explore the possible cell-mediated immune mechanisms of HBsAg positive HBV infection on the survival of DLBCL. Methods： A total of 294 newly diagnosed DLBCL patients were enrolled in this cohort study. Four-color flow cytometric method was used to enumerate the absolute number of CD3＋, CD4＋, CDS＋ T lymphocytes and the CD4＋/CD8＋ ratio in peripheral blood samples, at the onset of disease, 2-4, 4-6 and 6-12 months after the initiation of chemotherapy, individually. Results： The absolute number of CD3＋, CD4＋, CD8＋ T lymphocytes in both groups were similar at the onset of disease; the count ofCD4＋ lymphocytes was lower in HBsAg positive group during 2 to 4 months after the initiation of chemotherapy, compared with that in the HBsAg negative group. During 4 to 12 months after chemotherapy, the CD4＋/CD8＋ ratio in peripheral blood samples was significantly lower in HBsAg positive group. Conclusion： For newly diagnosed DLBCL patients who received chemotherapy, the dynamic nature of cell mediated immune response was characterized as a low counts of CD4＋ T lymphocyte during the first several cycles of chemotherapy followed by a decreased circulating CD4＋/CD8＋ ratio. Depressions of cell immunity after chemotherapy in HBsAg positive DLBCL patients were greater and prolonged.