免疫细胞亚群与多发性骨髓瘤临床预后因子相关性研究
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摘要
目的探讨免疫细胞亚群与多发性骨髓瘤临床预后因子相关性。方法我院收治的32例多发性骨髓瘤患者,根据年龄不同分为45～60岁组(18例)和60岁以上组(14例),选取同年龄段的健康者作为对照,分别为62例和42例。各组采用流式细胞仪进行淋巴细胞亚群免疫表型检测,采用荧光原位杂交技术进行细胞遗传学危险度分层,采用免疫比浊法检测β2-MG水平。结果与对照组比较,不同年龄段的两组患者CD8~+HLADR~+/CD8~+百分比、CD8~+CD38~+/CD8~+百分比明显升高(P <0. 05),CD4~+CD28~+/CD4~+百分比明显降低(P <0. 05);细胞遗传学(FISH)高危组CD8~+T淋巴细胞、CD8~+HLADR~+/CD8~+细胞占比高于FISH无高危组,CD4~+CD28~+/CD4~+细胞占比低于FISH无高危组(P <0. 05); CD8~+细胞百分比、CD8~+HLADR~+/CD8~+百分比与血清β2-MG水平呈正相关,CD4~+CD28~+/CD4~+百分比与β2-MG呈负相关(P <0. 05)。结论多发性骨髓瘤外周血CD4~+T细胞功能缺陷,CD8~+T淋巴细胞异常增生以及CD8~+T细胞功能异常活化与细胞遗传学危险度分层及预后存在一定的相关性,这可能成为疾病预后的判断指标,值得临床深入研究。
Objective To investigate the correlation between immune cell subsets and clinical prognostic factors of multiple myeloma.Methods Thirty-two patients with multiple myeloma admitted to our hospital were divided into 45-60 years old group( n =18) and >60 years old group( n = 14) according to the age of patients.At the same period,age-matched healthy subjects were taken as controls( n = 62 and n = 42 for the different age groups,respectively).Flow cytometry was used to detect the lymphocyte subsets.Fluorescence in situ hybridization( FISH) was used to stratify the risk of cytogenetics. Immunoturbidimetric assay was used to detect β2-MG level.Results Compared with the control group,percentages of CD8~+HLADR~+/CD8~+and CD8~+CD38~+/CD8~+were significantly increased while percentage of CD4~+CD28~+/CD4~+was significantly decreased in both age groups of the patients( P < 0. 05).The results of FISH showed that CD8~+T lymphocytes and CD8~+HLADR~+/CD8~+was significantly higher while CD4~+CD28~+/CD4~+cells were significant lower in cytogenetic high-risk group than those in non high-risk group( P < 0. 05). Percentages of CD8~+cells and CD8~+HLADR~+/CD8~+cells were positively correlated with serum β2-MG level( P < 0. 05) while percentage of CD4~+CD28~+/CD4~+cells was negatively correlated with β2-MG level( P < 0. 05). Conclusion In peripheral blood of multiple myeloma,defection of CD4~+T cell function,abnormal proliferation of CD8~+T lymphocyte and dysfunctional activation of CD8~+T cells have a certain correlation with cytogenetic risk stratification and prognosis.These may become the judging indicators for disease prognosis.It is worthy of in-depth clinical research.
Objective To investigate the correlation between immune cell subsets and clinical prognostic factors of multiple myeloma.Methods Thirty-two patients with multiple myeloma admitted to our hospital were divided into 45-60 years old group( n =18) and >60 years old group( n = 14) according to the age of patients.At the same period,age-matched healthy subjects were taken as controls( n = 62 and n = 42 for the different age groups,respectively).Flow cytometry was used to detect the lymphocyte subsets.Fluorescence in situ hybridization( FISH) was used to stratify the risk of cytogenetics. Immunoturbidimetric assay was used to detect β2-MG level.Results Compared with the control group,percentages of CD8~+HLADR~+/CD8~+and CD8~+CD38~+/CD8~+were significantly increased while percentage of CD4~+CD28~+/CD4~+was significantly decreased in both age groups of the patients( P < 0. 05).The results of FISH showed that CD8~+T lymphocytes and CD8~+HLADR~+/CD8~+was significantly higher while CD4~+CD28~+/CD4~+cells were significant lower in cytogenetic high-risk group than those in non high-risk group( P < 0. 05). Percentages of CD8~+cells and CD8~+HLADR~+/CD8~+cells were positively correlated with serum β2-MG level( P < 0. 05) while percentage of CD4~+CD28~+/CD4~+cells was negatively correlated with β2-MG level( P < 0. 05). Conclusion In peripheral blood of multiple myeloma,defection of CD4~+T cell function,abnormal proliferation of CD8~+T lymphocyte and dysfunctional activation of CD8~+T cells have a certain correlation with cytogenetic risk stratification and prognosis.These may become the judging indicators for disease prognosis.It is worthy of in-depth clinical research.
引文
[1]李美岩,邱广斌.不分泌型多发性骨髓瘤继发肾淀粉样变性1例报道[J].检验医学与临床,2014,8(6):156-157.
[2]肖蓉.多发性骨髓瘤患者血清胱抑素C水平测定[J].华西医学,2012,7(2):69-70.
[3]丁江华,袁利亚,陈国安.微小RNA-21与多发性骨髓瘤的相关性[J].重庆医学,2013,11(1):15-16.
[4]Hyoeun S,Joo Hee H,Hyewon L,et al.Expression of Myeloid Antigen in Neoplastic Plasma Cells Is Related to Adverse Prognosis in Patients with Multiple Myeloma[J].BioMed Research International,2014,2014:1354.
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[7]Wang S,Hong S,Yang J,et al.Optimizing immunotherapy in multiple myeloma:Restoring the function of patients‘monocyte-derived dendritic cells by inhibiting p38or activating MEK/ERK MAPK and neutralizing interleukin-6 in progenitor cells[J]. Blood,2006,108(13):145.
[8]Mozaffari F,Hansson L,Kiaii S,et al.Signalling molecules and cytokine production in T cells of multiple myeloma-increased abnormalities with advancing stage[J].British Journal of Haematology,2004,124(3):22.
[9]马勇,汪兴洪.多发性骨髓瘤治疗进展[J].亚太传统医药,2012,4(4):14-15.
[10]杨秀,王庆文,王金泉,等.多发性骨髓瘤肾损害尿蛋白性质的分析及临床意义[J].医学研究生学报,2012,8(3):74.
[11]赵英男,朱杰.胞浆轻链测定在多发性骨髓瘤的微小残留病变检测中的价值[J].武警医学,2014,9(1):58-59.
[12]Brown R,Murray A,Pope B,et al.B7+T cells in myeloma:an acquired marker of prior chronic antigen presentation[J]. Leukemia and Lymphoma,2004,45(2):38-39.
[13]裴仁治,唐善浩,马俊霞,等.趋化因子及其受体与多发性骨髓瘤的预后关系[J].中华内科杂志,2012,51(10):798-799.
[14]丁海,王森,高硕,等.多发性骨髓瘤患者外周血淋巴细胞亚群的变化及临床意义[J].检验医学与临床,2017,14(13):1880-1882.
[15]Feyler S,Scott G B,Parrish C,et al.Tumour Cell Generation of Inducible Regulatory T-Cells in Multiple Myeloma Is ContactDependent and Antigen-Presenting Cell-Independent[J].Plos One,2012,7(5):e35981.
[2]肖蓉.多发性骨髓瘤患者血清胱抑素C水平测定[J].华西医学,2012,7(2):69-70.
[3]丁江华,袁利亚,陈国安.微小RNA-21与多发性骨髓瘤的相关性[J].重庆医学,2013,11(1):15-16.
[4]Hyoeun S,Joo Hee H,Hyewon L,et al.Expression of Myeloid Antigen in Neoplastic Plasma Cells Is Related to Adverse Prognosis in Patients with Multiple Myeloma[J].BioMed Research International,2014,2014:1354.
[5]张磊,孙金芳,刘树业.常规生化检查在初诊多发性骨髓瘤患者中的应用价值[J].国际检验医学杂志,2012,7(4):56-58.
[6]胡十齐,周新伏,罗自勉.多发性骨髓瘤患者预后相关因素分析[J].河北医学,2012,7(6):85-86.
[7]Wang S,Hong S,Yang J,et al.Optimizing immunotherapy in multiple myeloma:Restoring the function of patients‘monocyte-derived dendritic cells by inhibiting p38or activating MEK/ERK MAPK and neutralizing interleukin-6 in progenitor cells[J]. Blood,2006,108(13):145.
[8]Mozaffari F,Hansson L,Kiaii S,et al.Signalling molecules and cytokine production in T cells of multiple myeloma-increased abnormalities with advancing stage[J].British Journal of Haematology,2004,124(3):22.
[9]马勇,汪兴洪.多发性骨髓瘤治疗进展[J].亚太传统医药,2012,4(4):14-15.
[10]杨秀,王庆文,王金泉,等.多发性骨髓瘤肾损害尿蛋白性质的分析及临床意义[J].医学研究生学报,2012,8(3):74.
[11]赵英男,朱杰.胞浆轻链测定在多发性骨髓瘤的微小残留病变检测中的价值[J].武警医学,2014,9(1):58-59.
[12]Brown R,Murray A,Pope B,et al.B7+T cells in myeloma:an acquired marker of prior chronic antigen presentation[J]. Leukemia and Lymphoma,2004,45(2):38-39.
[13]裴仁治,唐善浩,马俊霞,等.趋化因子及其受体与多发性骨髓瘤的预后关系[J].中华内科杂志,2012,51(10):798-799.
[14]丁海,王森,高硕,等.多发性骨髓瘤患者外周血淋巴细胞亚群的变化及临床意义[J].检验医学与临床,2017,14(13):1880-1882.
[15]Feyler S,Scott G B,Parrish C,et al.Tumour Cell Generation of Inducible Regulatory T-Cells in Multiple Myeloma Is ContactDependent and Antigen-Presenting Cell-Independent[J].Plos One,2012,7(5):e35981.