Correlations between CD4+CD25+Treg,sCD30 and Clinical Characteristics of Lymphoma and Their Value in Predicting Infection after Chemotherapy
-
摘要:
目的 探讨淋巴瘤患者外周血CD4+CD25+调节性T细胞(CD4+CD25+Treg)、可溶性CD30(sCD30)表达及意义。 方法 选取2018年1月至2022年12月北京航天总医院收治的83例淋巴瘤患者作为研究对象,统计其外周血CD4+CD25+Treg、sCD30表达,Spearman分析外周血CD4+CD25+Treg、sCD30表达与骨髓浸润相关性,同时将研究对象根据利妥昔单抗化疗后有无感染分为感染组(n = 26)和非感染组(n = 57),比较2组外周血CD4+CD25+Treg、sCD30表达及差值,绘制受试者工作特征曲线(ROC)及曲线下面积(AUC)分析预测效能。 结果 研究组有骨髓浸润患者外周血CD4+CD25+Treg、sCD30表达高于无骨髓浸润患者(P < 0.05);淋巴瘤患者外周血CD4+CD25+Treg、sCD30表达与骨髓浸润呈正相关(r=0.612、0.634,P < 0.05);化疗后感染组外周血Tregs、sCD30表达高于非感染组,差值高于非感染组(P < 0.05);ROC曲线显示,外周血CD4+CD25+Treg、sCD30差值联合预测淋巴瘤患者化疗后感染的AUC为0.916(0.834~0.965),优于单一预测。 结论 淋巴瘤外周血CD4+CD25+Treg、sCD30呈高表达,其值与骨髓浸润呈正相关,联检有助于提高化疗后感染预测效能,指导临床诊治。 Abstract:Objective To investigate the expression and significance of CD4+CD25+ regulatory T cells (CD4+CD25+Treg) and soluble CD30 (sCD30) in peripheral blood of lymphoma patients. Methods A total of 83 lymphoma patients admitted to Beijing Aerospace General Hospital from January 2018 to December 2022 were selected as the research subjects, and their peripheral blood CD4+CD25+Treg and sCD30 expressions were statistically analyzed. Spearman analysis was used to investigate the correlation between peripheral blood CD4+CD25+Treg and sCD30 expressions and bone marrow infiltration. At the same time, the research subjects were divided into an infection group (n = 26) and a non-infection group (n = 57) according to the presence or absence of infection after rituximab chemotherapy. The expressions and differences of peripheral blood CD4+CD25+Treg and sCD30 in the two groups were compared, and the receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive efficacy. Results The expression of CD4+CD25+Treg and sCD30 in peripheral blood of patients with bone marrow infiltration was higher than that of patients without bone marrow infiltration in the research group (P < 0.05); the expression of CD4+CD25+Treg and sCD30 in peripheral blood of lymphoma patients was positively correlated with bone marrow infiltration (r = 0.612, 0.634, P < 0.05); the expression of Tregs and sCD30 in peripheral blood of the infection group after chemotherapy was higher than that of the non-infection group, and the difference was higher than that of the non-infection group (P < 0.05); the ROC curve showed that the combined prediction of the difference of CD4+CD25+Treg and sCD30 in peripheral blood for the infection after chemotherapy in lymphoma patients had an AUC of 0.916 (0.834-0.965), which was superior to single prediction. Conclusion The high expression of CD4+CD25+Treg and sCD30 in peripheral blood of lymphoma patients is positively correlated with bone marrow infiltration. Combined testing can improve the predictive efficacy of infection after chemotherapy and guide clinical diagnosis and treatment. -
Key words:
- Lymphoma /
- Bone marrow infiltration /
- Chemotherapy /
- Infection /
- CD4+CD25+Treg /
- sCD30
-
表 1 研究组不同临床特征外周血CD4+CD25+Treg、sCD30表达比较($\bar x \pm s $)
Table 1. Comparison of peripheral blood CD4+CD25+Treg and sCD30 expression in the study groups with different clinical characteristics ($\bar x \pm s $)
临床特征 CD4+CD25+Treg(%) sCD30(kU/L) 性别 男性(n = 33) 2.50±0.41 159.23±19.46 女性(n = 50) 2.42±0.55 158.62±20.30 t 0.714 0.136 P 0.477 0.892 年龄(岁) <60(n = 43) 2.48±0.44 158.12±20.66 ≥60(n = 40) 2.42±0.51 159.66±21.17 t 0.575 0.335 P 0.567 0.738 体质量指数(Kg/m2) <18.5(n = 37) 2.42±0.50 158.12±20.91 18.5~24.0(n = 28) 2.47±0.44 159.04±20.25 ≥24.0(n = 18) 2.48±0.46 160.10±19.43 F 0.136 0.059 P 0.873 0.943 骨髓浸润 有(n = 18) 3.31±0.85 179.42±26.34 无(n = 65) 2.21±0.63 153.17±19.89 t 6.055 4.604 P <0.001* <0.001* 肿瘤分期 Ⅱ期(n = 38) 2.50±0.67 158.93±20.21 Ⅲ期(n = 45) 2.41±0.75 158.80±20.56 t 0.572 0.030 P 0.570 0.977 全身症状 有(n = 33) 2.41±0.66 158.79±21.15 无(n = 50) 2.48±0.73 158.91±20.78 t 0.444 0.026 P 0.658 0.980 *P < 0.05。 表 2 感染组和非感染组外周血CD4+CD25+Treg、sCD30表达比较($\bar x \pm s $)
Table 2. Comparison of peripheral blood CD4+CD25+Treg,sCD30 expression between infection and non-infection groups ($ \bar x \pm s $)
项目 感染组(n = 26) 非感染组(n = 57) χ2 P CD4+CD25+Treg(%) 化疗前 2.50±0.66 2.43±0.70 0.430 0.668 化疗后 2.86±0.81 2.26±0.74 3.326 <0.001* 差值 0.36±0.11 0.17±0.06 10.177 <0.001* sCD30(kU/L) 化疗前 159.43±16.68 158.60±17.42 0.204 0.840 化疗后 172.22±23.34 152.77±18.89 4.035 <0.001* 差值 12.79±2.56 5.83±0.78 18.815 <0.001* 差值取绝对值;*P < 0.05。 表 3 外周血CD4+CD25+Treg、sCD30单一及联合预测化疗后感染价值
Table 3. Peripheral blood CD4+CD25+ Treg,sCD30 single and combined predictive value of post-chemotherapy infection
项目 AUC(95%CI) 截断值 敏感度(%) 特异度(%) P 化疗后 CD4+CD25+Treg 0.725(0.616~0.817) >2.62% 61.54 78.95 <0.001* sCD30 0.766(0.660~0.852) >170.21 kU/L 61.54 91.23 <0.001* 两者联合 0.892(0.805~0.950) − 84.62 82.46 <0.001* 差值 CD4+CD25+Treg 0.809(0.708~0.887) >0.34 % 73.08 91.23 <0.001* sCD30 0.827(0.728~0.901) >12.08 kU/L 73.08 78.95 <0.001* 两者联合 0.916(0.834~0.965) − 84.62 85.96 <0.001* *P < 0.05。 -
[1] Olsen E A,Whittaker S,Willemze R,et al. Primary cutaneous lymphoma: Recommendations for clinical trial design and staging update from the ISCL,USCLC,and EORTC[J]. Blood,2022,140(5):419-437. doi: 10.1182/blood.2021012057 [2] De Roos A J,Fritschi L,Ward M H,et al. Herbicide use in farming and other jobs in relation to non-Hodgkin's lymphoma (NHL) risk[J]. Occup Environ Med,2022,79(12):795-806. doi: 10.1136/oemed-2022-108371 [3] 李巧,王珂. 利妥昔单抗联合CHOP方案治疗弥漫大B细胞淋巴瘤的疗效观察[J]. 中国肿瘤临床与康复,2021,28(10):1162-1164. [4] 包仁君,徐选福,莫文辉,等. 非霍奇金淋巴瘤患者R-CHOP 化疗后肝损伤的易感因素及异甘草酸镁预防性保肝作用研究[J]. 世界临床药物,2022,43(10):1362-1368. [5] Grygorowicz M A,Borycka I S,Nowak E,et al. Lenalidomide potentiates cd4+cd25+treg-related suppression of lymphoma B-cell proliferation[J]. Clin Exp Med,2017,17(2):193-207. doi: 10.1007/s10238-016-0411-8 [6] Rhee J,Birmann B M,De Roos A J,et al. Circulating immune markers and risks of non-Hodgkin lymphoma subtypes: A pooled analysis[J]. Int J Cancer,2023,152(5):865-878. doi: 10.1002/ijc.34299 [7] 中国抗癌协会淋巴瘤专业委员会,中国医师协会肿瘤医师分会,中国医疗保健国际交流促进会肿瘤内科分会,等. 中国淋巴瘤治疗指南(2021年版)[J]. 中华肿瘤杂志,2021,43(7):707-735. [8] 刘蕾,易琴,聂甜,等. NHL化疗患者NLR,PLR,RDW变化及对肺部感染的预测价值[J]. 分子诊断与治疗杂志,2021,13(11):1800-1804. [9] Wang Y,Liu X,Yan P,et al. Association between type 1 and type 2 diabetes and risk of non-Hodgkin's lymphoma: A meta-analysis of cohort studies[J]. Diabetes Metab,2020,46(1):8-19. doi: 10.1016/j.diabet.2019.04.006 [10] Gerlach M M,Juskevicius D,Vela V,et al. Bone marrow infiltration of angioimmunoblastic T-cell lymphoma: Identification and prognostic impact of histologic patterns and diagnostic application of ancillary phenotypic and molecular analyses[J]. Arch Pathol Lab Med,2020,144(5):602-611. doi: 10.5858/arpa.2019-0007-OA [11] Alonso-Álvarez S,Alcoceba M,García-Álvarez M,et al. Biological features and prognostic impact of bone marrow infiltration in patients with diffuse large B-cell lymphoma[J]. Cancers (Basel),2020,12(2):474. doi: 10.3390/cancers12020474 [12] 陈香,乔文礼,宋建华,等. 继发性骨淋巴瘤的^(18)F-FDG PET/CT影像诊断及与骨髓活检诊断效能的比较[J]. 现代肿瘤医学,2021,29(14):6. [13] Shin H J,Kim D Y,Chung J,et al. Prognostic impact of peripheral blood T-cell subsets at the time of diagnosis on survival in patients with diffuse large B-cell lymphoma[J]. Acta Haematol,2021,144(4):427-437. doi: 10.1159/000510912 [14] Liu B C,Wei C Y. Hypoxia induces overexpression of ccl28 to recruit treg cells to enhance angiogenesis in lung adenocarcinoma[J]. J Environ Pathol Toxicol Oncol,2021,40(1):65-74. doi: 10.1615/JEnvironPatholToxicolOncol.2020035859 [15] Wang W,Ye C H,Deng Z F,et al. Cd4+cd25+ regulatory T cells decreased future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy[J]. World J Gastrointest Surg,2023,15(5):917-930. doi: 10.4240/wjgs.v15.i5.917 [16] 王欣,梁艳丽,李艳秋,等. 血清TK1和sCD30水平与T细胞淋巴瘤患者临床特征的相关性[J]. 海军医学杂志,2022,43(1):65-69. [17] Levin L I,Ramirez C M,Liao E L,et al. Longitudinal changes in immune activation serum biomarkers prior to diagnosis and risk of B-cell nhl subtypes[J]. Cancer Epidemiol Biomarkers Prev,2023,32(2):233-241. doi: 10.1158/1055-9965.EPI-22-0247 [18] 陈瑜,陶石,胡敏,等. 血清Flt3L和Gas6水平对非霍奇金淋巴瘤患者利妥昔单抗化疗后肺部感染预测价值分析[J]. 分子诊断与治疗杂志,2022,14(4):652-655,659. [19] Lee J,Lee R,Beck K S,et al. Migratory pneumonia in prolonged SARS-COV-2 infection in patients treated with B-cell depletion therapies for B-cell lymphoma[J]. Korean J Radiol,2023,24(4):362-370. doi: 10.3348/kjr.2022.0844 [20] 康从越,夏永寿,叶先梅,等. 淋巴瘤患者化疗后肺部感染病原学分析及免疫球蛋白变化[J]. 中国肿瘤临床与康复,2021,28(9):1111-1115. [21] 李碧云,韩亚辉,殷楚云,等. 利妥昔单抗治疗儿童及青少年成熟B细胞非霍奇金淋巴瘤疗效及安全性的Meta分析[J]. 中国当代儿科杂志,2023,25(1):51-59. [22] 谷振阳,王全顺,黄文荣,等. 程序性死亡因子-1抑制剂治疗合并中枢神经系统受累的复发/难治性弥漫大B细胞淋巴瘤患者的临床分析并文献复习[J]. 国际输血及血液学杂志,2021,44(4):336-342. [23] 张艳彬,陈文昆,周寅,等. NLRP3炎性小体水平检测在非霍奇金淋巴瘤患者免疫治疗相关细胞因子风暴及化疗相关间质性肺炎中的预测价值分析[J]. 疑难病杂志,2022,21(5):485-491,506.