Differences of platelet activation and T cell function in patients with sepsis with different prognosis
-
摘要: 目的 探讨不同预后脓毒症患者血小板活化程度及T细胞功能水平的差异性及与预后不良风险的相关性。方法 回顾性分析2020年1月—2023年2月就诊于新疆医科大学第七附属医院的89例脓毒症患者。根据患者住院期间感染是否得到控制、出院后3个月内预后情况划分为预后良好组(61例)和预后不良组(28例)。对比两组患者性别、年龄、快速序贯器官衰竭估计评分等一般临床资料；血小板因子4(platelet factor 4，PF4)、P-选择素及蛋白激酶Cδ等血小板活化相关血清学标志物；CD62p、CD40L及CD63等血小板活化相关膜表面标志物；CD4+T细胞比例、CD8+T细胞比例及CD4+T/CD8+T比值等T细胞功能相关指标。分析不同预后患者间各指标的差异，通过Spearman相关性分析及多因素logistic回归分析筛选脓毒症患者预后不良的危险因素。结果 预后不良组患者的血清PF4、P-选择素水平、血小板CD62p、CD40L及CD63阳性率均显著高于预后良好组患者，差异有统计学意义(P < 0.05)；预后不良组患者的CD4+T细胞比例、CD4+/CD8+比值显著低于预后良好组患者，差异有统计学意义(P < 0.05)；脓毒症患者预后不良与患者血清PF4、P-选择素水平、血小板CD62p、CD40L及CD63阳性率呈显著正相关，与CD4+T细胞比例及CD4+/CD8+比值呈显著负相关，差异有统计学意义(P < 0.05)；脓毒症患者血小板CD62p及CD63阳性率增加，CD4+T细胞比例及CD4+/CD8+比值降低均是预后不良的危险因素，差异有统计学意义(P < 0.05)。结论 不同预后情况的脓毒症患者血小板活化程度及T细胞功能存在较大差异，其中CD62p及CD63等血小板活化相关膜指标阳性率增加、CD4+T细胞比例及CD4+/CD8+比值等T细胞功能指标降低可能提示脓毒症患者预后不良，监测相关指标将有利于早期评估脓毒症患者病情及预后情况。Abstract: Objective To investigate the difference of platelet activation and T cell function in patients with sepsis with different prognosis and the correlation with the risk of poor prognosis.Methods Eighty-nine patients with sepsis from January 2020 to February 2023 were analyzed. According to whether the infection was controlled during hospitalization and the prognosis within 3 months after discharge, the patients were divided into two groups: good prognosis group(n=61) and poor prognosis group(n=28). The general clinical data such as sex, age, quick sequential organ failure assessment, platelet activation related serological markers such as platelet factor 4(PF4), P-selectin and protein kinase C δ, platelet activation related membrane markers such as CD62p, CD40L and CD63, and T cell function related indexes such as CD4+T cell proportion, CD8+T cell proportion and CD4+T/CD8+T ratio were compared between the two groups. The differences of various indexes among patients with different prognosis were analyzed, and the risk factors of poor prognosis in patients with sepsis were screened by Spearman correlation analysis and multivariate logistic regression analysis.Results The levels of serum PF4, P-selectin, platelet CD62p, CD40L and CD63 in patients with poor prognosis were significantly higher than patients with good prognosis(P < 0.05). The proportion of CD4+T cells and CD4+/CD8+ ratio in patients with poor prognosis were significantly lower than patients with good prognosis(P < 0.05). The poor prognosis of patients with sepsis was positively correlated with the levels of serum PF4, P-selectin, platelet CD62p, CD40L and CD63, and negatively correlated with the proportion of CD4+T cells and the ratio of CD4+/CD8+(P < 0.05). The increase of platelet CD62p and CD63 positive rate and the decrease of CD4+T cell proportion and CD4+/CD8+ ratio were risk factors for poor prognosis in patients with sepsis(P < 0.05).Conclusion There are significant differences in platelet activation and T cell function in patients with sepsis with different prognosis. The increase in the positive rate of platelet activation related membrane indexes such as CD62p and CD63 and the decrease of T cell function indexes such as CD4+T cell proportion and CD4+/CD8+ ratio may indicate a poor prognosis of septic patients. Monitoring related indexes will be helpful to early evaluate the condition and prognosis of septic patients.
-
Key words:
- sepsis /
- platelet activation /
- T cell function /
- prognosis
-
-
表 1 2组患者一般临床资料对比
X±S 组别 性别/例(%) 年龄/岁 入院前病程/d qSOFA WBC/(×109/L) PLT/(×109/L) 住院时间/d 男 女 预后不良组(28例) 17(60.71) 11(39.29) 48.8±6.0 5.36±2.38 1.39±0.79 12.14±2.52 189.08±44.61 11.86±3.33 预后良好组(61例) 31(50.82) 30(49.18) 49.8±5.4 5.97±2.06 1.31±0.67 13.30±3.19 189.62±43.60 12.26±2.77 χ2/t 0.756 0.736 1.237 0.503 1.685 0.053 0.600 P 0.385 0.464 0.220 0.616 0.096 0.958 0.550 
下载: 导出CSV
表 2 2组患者血小板活化相关血清学标志物比较
X±S 组别 PF4/(μg/mL) P-选择素/(μg/mL) PKCδ/(ng/mL) 预后不良组(28例) 392.36±106.22 54.75±20.48 21.62±5.99 预后良好组(61例) 300.57±95.80 40.68±19.01 21.37±5.47 t 4.056 3.165 0.188 P < 0.001 0.002 0.851
下载: 导出CSV
表 3 2组患者血小板活化相关血清学标志物比较
X±S 组别 CD62p/% CD40L/% CD63/% 预后不良组(28例) 1.76±0.54 2.23±0.57 3.64±2.56 预后良好组(61例) 1.17±0.40 1.86±0.43 2.12±0.58 t 5.802 3.398 4.430 P < 0.001 0.001 < 0.001
下载: 导出CSV
表 4 2组患者T细胞功能相关指标比较
X±S 组别 CD4+T细胞比例/% CD8+T细胞比例/% CD4+/CD8+比值 预后不良组(28例) 29.44±7.95 26.48±7.72 1.28±0.27 预后良好组(61例) 37.13±9.05 28.07±8.94 1.58±0.45 t 3.861 0.811 3.341 P < 0.001 0.419 0.001
下载: 导出CSV
表 5 脓毒症患者预后不良与各差异性指标的相关性
项目 PF4 P-选择素 CD62p CD40L CD63 CD4+T细胞比例 CD4+/CD8+比值 r 0.398 0.300 0.507 0.323 0.540 -0.373 -0.381 P < 0.001 0.004 < 0.001 0.002 < 0.001 < 0.001 < 0.001
下载: 导出CSV
表 6 脓毒症患者预后不良的危险因素
观察指标 β SE Wald χ2 P OR 95%CI 下限 上限 PF4 0.009 0.005 3.483 0.062 1.009 1.000 1.018 P-选择素 0.039 0.028 1.883 0.170 1.040 0.983 1.099 CD62p 3.196 1.294 6.104 0.013 24.444 1.936 308.579 CD40L 0.649 0.977 0.441 0.507 1.913 0.282 12.985 CD63 2.006 0.822 5.950 0.015 7.436 1.483 37.274 CD4+T细胞比例 -0.160 0.066 5.889 0.015 0.852 0.748 0.970 CD4+/CD8+比值 -2.580 1.207 4.572 0.033 0.076 0.007 0.806
下载: 导出CSV
-
[1] 付绪哲, 柳英杰, 牛明明, 等. 脓毒症免疫抑制机制的研究进展[J]. 中国临床研究, 2023, 36(5): 741-745.
[2] 李若柠, 郭展立, 王媛, 等. 血小板内皮聚集受体1及其介导的信号通路在血小板和内皮细胞中的作用研究进展[J]. 中国临床药理学与治疗学, 2023, 28(4): 438-444.
[3] 卫莹, 沈明花. 血小板在炎症反应中的作用研究进展[J]. 延边大学医学学报, 2022, 45(4): 303-306.
[4] 暴蓉, 苗林子, 哈斯朝鲁, 等. 脓毒症患者免疫功能的研究进展[J]. 临床检验杂志, 2022, 40(11): 853-856.
[5] 邢信昊, 陈林林, 凌忠毅, 等. 免疫治疗纠正脓毒症免疫麻痹的研究进展[J]. 药学实践与服务, 2023, 41(1): 1-7, 35.
[6] 陈侃政, 沈巨信, 孙健. 自噬与脓毒症T细胞功能异常相关性的研究进展[J]. 中国免疫学杂志, 2023, 39(6): 1331-1336. doi: 10.3969/j.issn.1000-484X.2023.06.045
[7] 曹钰, 柴艳芬, 邓颖, 等. 中国脓毒症/脓毒性休克急诊治疗指南(2018)[J]. 临床急诊杂志, 2018, 19(9): 567-588. https://lcjz.whuhzzs.com/article/doi/10.13201/j.issn.1009-5918.2018.09.001
[8] 李明, 周志刚. 血小板相关参数在脓毒症中临床意义的研究进展[J]. 疑难病杂志, 2021, 20(4): 423-427. doi: 10.3969/j.issn.1671-6450.2021.04.023
[9] 樊柳汝, 李金兰, 李筱妍. 脓毒症生物标志物研究进展[J]. 中国急救医学, 2022, 42(7): 620-624.
[10] 王瀚黎, 田圆, 梁群. 中性粒细胞胞外诱捕网在脓毒症中的作用机制与靶点[J]. 疑难病杂志, 2022, 21(11): 1206-1210. doi: 10.3969/j.issn.1671-6450.2022.11.019
[11] 朱鹏, 余跃天, 潘纯. 脓毒症相关的免疫抑制: 生物标志物的监测与挑战[J]. 临床内科杂志, 2021, 38(9): 591-593. doi: 10.3969/j.issn.1001-9057.2021.09.005
[12] 王静, 乔佑杰. 脓毒症相关生物标志物的研究进展[J]. 疑难病杂志, 2023, 22(5): 540-545.
[13] Mehic D, Machacek J, Schramm T, et al. Platelet function and soluble P-selectin in patients with primary immune thrombocytopenia[J]. Thromb Res, 2023, 223: 102-110. doi: 10.1016/j.thromres.2023.01.012
[14] Secor D, Li F, Ellis CG, et al. Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries[J]. Intensive Care Med, 2010, 36(11): 1928-1934. doi: 10.1007/s00134-010-1969-3
[15] Warkentin TE. Platelet-activating anti-PF4 disorders: An overview[J]. Semin Hematol, 2022, 59(2): 59-71. doi: 10.1053/j.seminhematol.2022.02.005
[16] Harper MT, Poole AW. PKCtheta in platelet activation[J]. Blood, 2009, 114(2): 489-492. doi: 10.1182/blood-2009-03-208454
[17] Tsai KL, Liang HJ, Yang ZD, et al. Early inactivation of PKCε associates with late mitochondrial translocation of Bad and apoptosis in ventricle of septic rat[J]. J Surg Res, 2014, 186(1): 278-286.
[18] Langer F, Ingersoll SB, Amirkhosravi A, et al. The role of CD40 in CD40L-and antibody-mediated platelet activation[J]. Thromb Haemost, 2005, 93(6): 1137-1146.
[19] Voss R, Morgenstern E, Waas W, et al. No increase in CD62P-positive single platelets after acute platelet activation in vivo[J]. Thromb Res, 2006, 117(4): 393-399.
[20] Wauters A, Esmaeilzadeh F, Bladt S, et al. Pro-thrombotic effect of exercise in a polluted environment: a P-selectin-and CD63-related platelet activation effect[J]. Thromb Haemost, 2015, 113(1): 118-124.
[21] Lishko VK, Yakubenko VP, Ugarova TP, et al. Leukocyte integrin Mac-1(CD11b/CD18, αMβ2, CR3) acts as a functional receptor for platelet factor 4[J]. J Biol Chem, 2018, 293(18): 6869-6882.
[22] Li JY, Chen RJ, Huang LT, et al. Embelin as a Novel Inhibitor of PKC in the Prevention of Platelet Activation and Thrombus Formation[J]. J Clin Med, 2019, 8(10): 1724.
[23] Chen CW, Mittal R, Klingensmith NJ, et al. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis[J]. J Immunol, 2017, 199(6): 1961-1966.
[24] Peng Y, Wang X, Yin S, et al. A new indicator: The diagnostic value of CD8+T/B lymphocyte ratio in sepsis progression[J]. Int J Immunopathol Pharmacol, 2022, 36: 3946320221123164.
[25] Guo L, Shen S, Rowley JW, et al. Platelet MHC class Ⅰ mediates CD8+ T-cell suppression during sepsis[J]. Blood, 2021, 138(5): 401-416.
[26] 陈正钢, 刘励军. 急诊脓毒症患者早期筛查生物标志物的研究现状与展望[J]. 临床急诊杂志, 2023, 24(2): 99-104. https://lcjz.whuhzzs.com/article/doi/10.13201/j.issn.1009-5918.2023.02.010
-