弥漫大B细胞淋巴瘤患者外周血可溶性白细胞介素-2受体 T细胞亚群及自然杀伤细胞检测的临床意义
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摘要
目的探讨弥漫大B细胞淋巴瘤(DLBCL)患者化疗前后外周血可溶性白细胞介素-2受体(sIL-2R)水平、T细胞亚群及自然杀伤(NK)细胞的变化及其临床意义。方法收集经病理确诊的初治DLBCL患者30例,分别在第1次化疗前、化疗第2个周期前采集静脉血,运用酶联免疫吸附测定(ELISA)法测定sIL-2R的水平,经流式细胞术检测T细胞亚群及NK细胞。结果 DLBCL患者化疗前组血清sIL-2R水平高于健康者及化疗后组(P均<0.05)。DLBCL患者化疗前组分组为Ⅲ～Ⅳ期亚组、有B症状亚组、化疗无效亚组血清sIL-2R水平分别高于Ⅰ～Ⅱ期亚组、有A症状亚组、化疗有效组(P均<0.05)。DLBCL患者化疗前组sIL-2R、CD4~+T细胞、NK细胞数及CD4~+/CD8~+比值均低于健康者(P均<0.05)。DLBCL患者化疗前组Ⅲ～Ⅳ期血清NK细胞数及CD4~+/CD8~+比值及血清CD8~+T细胞计数与Ⅰ～Ⅱ期比较差异有统计学意义(P均<0.05)。化疗无效组CD4~+T细胞计数、NK细胞及CD4~+/CD8~+比值均低于化疗有效组(P均<0.05)。DLBCL患者化疗前组血清sIL-2R的表达水平与CD4~+T细胞计数、CD4~+/CD8~+及NK细胞计数呈负相关(P<0.01)。结论 DLBCL化疗前高表达sIL-2R与细胞免疫功能低下密切相关,与临床分期、疾病进展相关。动态检测sIL-2R、T细胞亚群及NK细胞的水平可作为DLBCL疗效判断的辅助指标。
Objective To determine the clinical significance of peripheral blood soluble interleukin-2 receptor(sIL-2 R), peripheral T lymphocyte subsets and NK cells in the patients with diffuse large B cell lymphoma(DLBCL)before and after chemotherapy. Methods Thirty patients with primary pathological diagnosis of DLBCL were included in the study. The venous blood was collected at the baseline of first chemotherapy and the second cycle of chemotherapy. ELISA assay was used to determine sIL-2 R level. The levels of peripheral blood T lymphocyte subsets and NK cells were measured by flow cytometry. Results The serum sIL-2 R level in DLBCL pre-chemotherapy group was significantly higher than that in post-chemotherapy group and healthy controls(all P <0.05). In DLBCL prechemotherapy subgroups, the serum sIL-2 R level in the stage Ⅲ-Ⅳ subgroup, symptom B subgroup, and chemotherapy-ineffective subgroup was higher than that in the stage Ⅰ-Ⅱ subgroup, symptom A subgroup, and chemotherapy-effective subgroup(all P<0.05). The number of CD4~+T cells and NK cells and ratio of CD4~+/CD8~+in the DLBCL prechemotherapy group were lower than those in the healthy controls(all P<0.05). The number of serum NK cells and ratio CD4~+/CD8~+and the serum CD8~+T cell count in the DLBCL pre-chemotherapy stage Ⅲ-Ⅳ subgroup were lower or higher than those in the stage Ⅰ-Ⅱ subgroup(all P<0.05). The CD4~+ T cell count, number of NK cells and CD4~+/CD8~+ratio in the chemotherapy-ineffective subgroup were lower than those in the chemotherapy-effective subgroup(all P <0.05). The expression level of serum sIL-2 R in DLBCL pre-chemotherapy group was negatively correlated with CD4~+T cell count(P<0.01), CD4~+/CD8~+ratio and NK cell count(P<0.01). Conclusion High expression of sIL-2 R before DLBCL chemotherapy is closely related to low cellular immune function, which is related to clinical stage and disease progression. Dynamic examination of sIL-2 R, T lymphocyte subsets and NK cell levels may be used as auxiliary parameters to the efficacy of DLBCL.
Objective To determine the clinical significance of peripheral blood soluble interleukin-2 receptor(sIL-2 R), peripheral T lymphocyte subsets and NK cells in the patients with diffuse large B cell lymphoma(DLBCL)before and after chemotherapy. Methods Thirty patients with primary pathological diagnosis of DLBCL were included in the study. The venous blood was collected at the baseline of first chemotherapy and the second cycle of chemotherapy. ELISA assay was used to determine sIL-2 R level. The levels of peripheral blood T lymphocyte subsets and NK cells were measured by flow cytometry. Results The serum sIL-2 R level in DLBCL pre-chemotherapy group was significantly higher than that in post-chemotherapy group and healthy controls(all P <0.05). In DLBCL prechemotherapy subgroups, the serum sIL-2 R level in the stage Ⅲ-Ⅳ subgroup, symptom B subgroup, and chemotherapy-ineffective subgroup was higher than that in the stage Ⅰ-Ⅱ subgroup, symptom A subgroup, and chemotherapy-effective subgroup(all P<0.05). The number of CD4~+T cells and NK cells and ratio of CD4~+/CD8~+in the DLBCL prechemotherapy group were lower than those in the healthy controls(all P<0.05). The number of serum NK cells and ratio CD4~+/CD8~+and the serum CD8~+T cell count in the DLBCL pre-chemotherapy stage Ⅲ-Ⅳ subgroup were lower or higher than those in the stage Ⅰ-Ⅱ subgroup(all P<0.05). The CD4~+ T cell count, number of NK cells and CD4~+/CD8~+ratio in the chemotherapy-ineffective subgroup were lower than those in the chemotherapy-effective subgroup(all P <0.05). The expression level of serum sIL-2 R in DLBCL pre-chemotherapy group was negatively correlated with CD4~+T cell count(P<0.01), CD4~+/CD8~+ratio and NK cell count(P<0.01). Conclusion High expression of sIL-2 R before DLBCL chemotherapy is closely related to low cellular immune function, which is related to clinical stage and disease progression. Dynamic examination of sIL-2 R, T lymphocyte subsets and NK cell levels may be used as auxiliary parameters to the efficacy of DLBCL.
引文
[1]中华医学会血液学分会、中国抗癌协会淋巴瘤专业委员会.中国弥漫大B细胞淋巴瘤诊断与治疗指南(2013年版)[J].中华血液学杂志,2013,34(9):816-819.
[2]Swerd low SH,Campo E,Pileri SA,et al.The 2016 revision of the world Health Organization classification of lymphoid neoplasms[J].Blood,2016,127(20):2375-2390.
[3]Boslooper K,Kibbelaar R,Storm H,et al.Treatment with rituximab,cyclophosphamide,doxorubicin,vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma:a populatioan-based cohort study on treatment,toxicity and outcome[J].Leuk Lymphoma,2014,55(3):526-532.
[4]Charbonneau B,Maurer MJ,Ansell SM,et al.Pretreatment circulating serum cytokines associated with follicular and diffuse large B-cell lymphoma:a clinic-based case-control study[J].Cytokine,2012,60(3):882-889.
[5]Tomita N,Sakai R,Fujisawa S,et al.SIL index,comprising stage,soluble interleukin-2 receptor,and lactate dehydrogenase,is a useful prognostic predictor in diffuse large B-cell lymphoma[J].Cancer Sci,2012,103(8):1518-1523.
[6]Hashimoto Y,Yokohama A,Saitoh A,et al.Prognostic importance of the soluble form of IL-2 receptorα(sIL-2Rα)and its relationship with surface expression of IL-2Rα(CD25)of lymphoma cells in diffuse large B-cell lymphoma treated with CHOP-like regimen with or without rituximab:a retrospective analysis of 338cases[J].J Clin Exp Hematopathol,2013,53(3):197-205.
[7]王琳,万岁桂.弥漫大B细胞淋巴瘤预后相关因素研究进展[J].白血病·淋巴瘤,2017,26(4):246-249.
[8]Dehghani M,Sharifpour S,Amirghofran Z,et al.Prognostic significance of T cell subsets in peripheral blood of B cell nonHodgkin′s lymphoma patients[J].Med Oncol,2012,29(4):2364-2371.
[9]葛华,杨新蔚,袁帆.非霍奇金淋巴瘤患者化疗前后T淋巴细胞亚群变化及临床意义[J].内科,2016,11(3):398-400.
[2]Swerd low SH,Campo E,Pileri SA,et al.The 2016 revision of the world Health Organization classification of lymphoid neoplasms[J].Blood,2016,127(20):2375-2390.
[3]Boslooper K,Kibbelaar R,Storm H,et al.Treatment with rituximab,cyclophosphamide,doxorubicin,vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma:a populatioan-based cohort study on treatment,toxicity and outcome[J].Leuk Lymphoma,2014,55(3):526-532.
[4]Charbonneau B,Maurer MJ,Ansell SM,et al.Pretreatment circulating serum cytokines associated with follicular and diffuse large B-cell lymphoma:a clinic-based case-control study[J].Cytokine,2012,60(3):882-889.
[5]Tomita N,Sakai R,Fujisawa S,et al.SIL index,comprising stage,soluble interleukin-2 receptor,and lactate dehydrogenase,is a useful prognostic predictor in diffuse large B-cell lymphoma[J].Cancer Sci,2012,103(8):1518-1523.
[6]Hashimoto Y,Yokohama A,Saitoh A,et al.Prognostic importance of the soluble form of IL-2 receptorα(sIL-2Rα)and its relationship with surface expression of IL-2Rα(CD25)of lymphoma cells in diffuse large B-cell lymphoma treated with CHOP-like regimen with or without rituximab:a retrospective analysis of 338cases[J].J Clin Exp Hematopathol,2013,53(3):197-205.
[7]王琳,万岁桂.弥漫大B细胞淋巴瘤预后相关因素研究进展[J].白血病·淋巴瘤,2017,26(4):246-249.
[8]Dehghani M,Sharifpour S,Amirghofran Z,et al.Prognostic significance of T cell subsets in peripheral blood of B cell nonHodgkin′s lymphoma patients[J].Med Oncol,2012,29(4):2364-2371.
[9]葛华,杨新蔚,袁帆.非霍奇金淋巴瘤患者化疗前后T淋巴细胞亚群变化及临床意义[J].内科,2016,11(3):398-400.