Correlation between MASP family expression levels and risk of poor prognosis in patients with sepsis
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摘要: 目的 对甘露聚糖结合凝集素相关丝氨酸蛋白酶(mannan-binding lectin associated serine proteases,MASP)家族表达水平与脓毒症患者预后风险的相关性进行分析。方法 将2018年1月—2022年12月于海南医学院第一附属医院诊治的113例脓毒症患者纳入研究,所有患者入院后均予补液、抗感染等规范化治疗,根据患者纳入研究28 d内是否死亡,将患者分为死亡组及存活组,比较两组患者一般临床资料及实验室指标,采用多因素logistic回归模型分析影响患者预后的因素,并对MASP家族表达水平与急性生理与慢性健康评分(acute physiology and chronic health evaluation,APACHE Ⅱ)评分相关性进行分析。结果 死亡组患者APACHE Ⅱ评分[(27.17±2.89)分]、白细胞[(15.34±2.11)×109/L]、超敏C反应蛋白[(26.19±3.87)mg/L]、MASP-1[(4 076.48±114.78)ng/L]、MASP-2[(58.75±6.31)ng/L]及MASP-3[(349.86±61.37)ng/L]水平显著高于存活组[(25.51±2.36)分,(14.23±1.64)×109/L,(28.36±3.92)mg/L,(3 848.65±89.24)ng/L,(48.22±3.54)ng/L,(216.93±54.74)ng/L],差异有统计学意义(均P < 0.05);白蛋白水平[(20.34±2.34)g/L]显著低于存活组[(24.78±2.61)g/L],差异有统计学意义(P < 0.001);多因素logistic回归分析示,高MASP-1水平(OR=1.019,P=0.019,95%CI:1.003~1.036)、MASP-2(OR=1.557,P=0.019,95%CI:1.078~2.306)及MASP-3(OR=1.033,P=0.047,95%CI:1.000~1.066)水平是影响患者预后的独立危险因素;Peason相关分析示:MASP-1、MASP-2及MASP-3水平与APACHE Ⅱ评分呈正相关(R=0.792,0.763,0.511,均P < 0.001)。结论 MASP家族表达水平升高与脓毒症患者不良预后呈显著正相关。
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关键词:
- 脓毒症 /
- 甘露聚糖结合凝集素相关丝氨酸蛋白酶 /
- 表达水平 /
- 不良预后 /
- 相关性
Abstract: Objective To analyze the correlation between the expression level of mannan-binding lectin associated serine proteases(MASP) family and the risk of poor prognosis of patients with sepsis.Methods One hundred and thirteen patients with sepsis diagnosed and treated in the First Affiliated Hospital of Hainan Medical College from January 2018 to December 2022 were included in the study. All patients were given standardized treatment such as fluid infusion and anti-infection after admission. According to whether the patients died within 28 days, they were divided into death group and survival group. Comparing the general clinical data and laboratory indexes such as MASP family expression levels of the two groups, and the multivariate logistic regression model was used to analyze the factors affecting the prognosis of the patients and the correlation between the expression level of MASP family and acute physiology and chronic health evaluation(APACHE Ⅱ)score.Results The level of APACHE Ⅱ score, white blood cell, hypersensitive C-reactive protein, MASP-1, MASP-2 and MASP-3 in the death group were significantly higher than that in the survival group (27.17±2.89)scores, (15.34±2.11)×109/L, (26.19±3.87)mg/L, (4 076.48±114.78)ng/L, (58.75±6.31)ng/L, (349.86±61.37)ng/L vs. (25.51±2.36)scores, (14.23±1.64)×109/L, (28.36±3.92)mg/L, (3 848.65±89.24)ng/L, (48.22±3.54)ng/L, (216.93±54.74)ng/L, all P < 0.05. While the level of albumin in the death group were significantly lower than those in the survival group(20.34±2.34)g/L vs. (24.78±2.61)g/L, P < 0.001. Multivariate logistic regression analysis showed that the high level of MASP-1(OR=1.019, P=0.019, 95%CI: 1.003-1.036)、MASP-2(OR=1.557, P=0.019, 95%CI: 1.078-2.306) and MASP-3(OR=1.033, P=0.047, 95%CI: 1.000-1.066) were independent risk factors which affecting the prognosis of patients. Pearson correlation analysis showed that the levels of MASP-1, MASP-2 and MASP-3 were positively correlated with APACHE Ⅱ score(R=0.792, 0.763, 0.511, all P < 0.001).Conclusion The increased expression of MASP family is positively correlated with poor prognosis in patients with sepsis. -
表 1 两组患者基线资料的比较
X±S 一般资料 死亡组(34例) 存活组(79例) t/χ2 P 年龄/岁 61.83±3.47 60.62±3.21 1.793 0.076 性别/例(%) 0.272 0.602 男 22(64.71) 47(59.49) 女 12(35.29) 32(40.51) BMI/(kg/m2) 22.29±2.86 22.76±2.91 0.791 0.430 感染部位/例(%) 2.105 0.551 呼吸系统 9(26.47) 25(31.65) 泌尿系统 4(11.76) 7(8.86) 消化系统 15(44.12) 32(40.51) 其他 6(17.65) 15(18.99) 基础疾病/例(%) 糖尿病 2(5.88) 4(5.06) 0.032 0.859 慢性阻塞性肺疾病 1(2.94) 1(1.27) 0.384 0.536 慢性肾脏病 1(2.94) 2(2.53) 0.015 0.901 脑梗死 2(5.88) 5(6.33) 0.008 0.928 高血压 1(2.94) 2(2.53) 0.015 0.901 心力衰竭 3(8.82) 8(10.13) 0.046 0.830 冠心病 4(11.76) 12(15.19) 0.229 0.632 APACHE Ⅱ评分/分 27.17±2.89 25.51±2.36 3.200 0.002 机械通气/例(%) 28(82.34) 54(68.35) 2.340 0.126 WBC/(×109/L) 15.34±2.11 14.23±1.64 3.699 < 0.001 PLT/(×109/L) 145.14±16.72 151.21±20.58 1.517 0.132 ALB/(g/L) 20.34±2.34 24.78±2.61 8.547 < 0.001 Scr/(μmol/L) 103.38±12.67 107.53±14.27 1.465 0.146 hs-CRP/(mg/L) 26.19±3.87 28.36±3.92 2.709 0.008 MASP-1/(ng/L) 4 076.48±114.78 3 848.65±89.24 11.389 < 0.001 MASP-2/(ng/L) 58.75±6.31 48.22±3.54 11.299 < 0.001 MASP-3/(ng/L) 349.86±61.37 216.93±54.74 11.411 < 0.001 表 2 影响患者预后的多因素logistic回归分析
变量 β SE Wald P OR 95%CI APACHE Ⅱ评分 0.191 0.242 0.619 0.431 1.210 0.752~1.946 WBC 0.040 0.346 0.013 0.908 0.961 0.488~1.892 ALB 0.286 0.207 1.913 0.167 0.751 0.501~1.127 hs-CRP 0.039 0.167 0.054 0.816 0.962 0.693~1.334 MASP-1 0.019 0.008 5.537 0.019 1.019 1.003~1.036 MASP-2 0.456 0.194 5.521 0.019 1.577 1.078~2.306 MASP-3 0.032 0.016 3.947 0.047 1.033 1.000~1.066 注:以预后为自变量,1=死亡;0=存活;因变量为APACHE Ⅱ评分、WBC、ALB、hs-CRP、MASP-1、MASP-2、MASP-3均为连续变量。 表 3 MASP家族表达水平与APACHE Ⅱ评分的相关性分析
MASP家族 APACHE Ⅱ R P MASP-1 0.792 < 0.001 MASP-2 0.763 < 0.001 MASP-3 0.511 < 0.001 -
[1] Liu D, Huang SY, Sun JH, et al. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options[J]. Mil Med Res, 2022, 9(1): 56.
[2] Seymour CW, Kennedy JN, Wang S, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis[J]. JAMA, 2019, 321(20): 2003-2017. doi: 10.1001/jama.2019.5791
[3] Gavelli F, Castello LM, Avanzi GC. Management of sepsis and septic shock in the emergency department[J]. Intern Emerg Med, 2021, 16(6): 1649-1661. doi: 10.1007/s11739-021-02735-7
[4] Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study[J]. Lancet, 2020, 395(10219): 200-211. doi: 10.1016/S0140-6736(19)32989-7
[5] Pierrakos C, Velissaris D, Bisdorff M, et al. Biomarkers of sepsis: time for a reappraisal[J]. Crit Care, 2020, 24(1): 287. doi: 10.1186/s13054-020-02993-5
[6] 程少文, 陈扬平, 张安强, 等. MBL2与MASPs家族蛋白质相互作用的生物信息学分析[J]. 海南医学院学报, 2019, 25(15): 1121-1124, 1129.
[7] Kristensen MK, Hansen MB, Madsen MB, et al. Complement Activation Is Associated With Mortality in Patients With Necrotizing Soft-Tissue Infections-A Prospective Observational Study[J]. Front Immunol, 2020, 11: 17. doi: 10.3389/fimmu.2020.00017
[8] 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
[9] Yan MY, Gustad LT, Nytro O. Sepsis prediction, early detection and identification using clinical text for machine learning: a systematic review[J]. J Am Med Inform Assoc, 2022, 29(3): 559-575. doi: 10.1093/jamia/ocab236
[10] Sinapidis D, Kosmas V, Vittoros V, et al. Progression into sepsis: an individualized process varying by the interaction of comorbidities with the underlying infection[J]. BMC Infect Dis, 2018, 18(1): 242. doi: 10.1186/s12879-018-3156-z
[11] Golomingi M, Kohler J, Jenny L, et al. Complement lectin pathway components MBL and MASP-1 promote haemostasis upon vessel injury in a microvascular bleeding model[J]. Front Immunol, 2022, 13: 948190. doi: 10.3389/fimmu.2022.948190
[12] 李旭, 马晓春. 严重感染出凝血障碍的认识和处理[J]. 中国实用内科杂志, 2021, 41(6): 466-469, 474.
[13] 任晓庆, 李琪, 闫本纯, 等. MASP-1联合血栓分子标志物对脓毒症合并DIC的诊断价值[J]. 中国现代医药杂志, 2022, 24(4): 43-46.
[14] Debreczeni ML, Németh Z, Kajdácsi E, et al. MASP-1 Increases Endothelial Permeability[J]. Front Immunol, 2019, 10: 991. doi: 10.3389/fimmu.2019.00991
[15] Németh Z, Debreczeni ML, Kajdácsi E, et al. Cooperation of Complement MASP-1 with Other Proinflammatory Factors to Enhance the Activation of Endothelial Cells[J]. Int J Mol Sci, 2023, 24(11): 9181. doi: 10.3390/ijms24119181
[16] 王文, 郭璐, 余雪梅, 等. 营养状态和MASP-2基因多态性与COPD并发肺部感染的关联性[J]. 中华医院感染学杂志, 2022, 32(4): 511-515.
[17] Gao T, Zhu L, Liu H, et al. Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation[J]. Signal Transduct Target Ther, 2022, 7(1): 318. doi: 10.1038/s41392-022-01133-5
[18] 衣丽华, 董岩, 郑丽莎, 等. 血清MASP-3、MBL、SDMA对老年急性缺血性脑卒中的诊断价值[J]. 疑难病杂志, 2022, 21(5): 456-460, 474.
[19] Rosbjerg A, Würzner R, Garred P, et al. MASP-1 and MASP-3 Bind Directly to Aspergillus fumigatus and Promote Complement Activation and Phagocytosis[J]. J Innate Immun, 2021, 13(4): 211-224. doi: 10.1159/000514546
[20] 郑林花, 张颖, 宋莎莎, 等. 血清MASP2、MASP3在IgA肾病中的作用[J]. 中国免疫学杂志, 2020, 36(1): 77-83.
[21] Machida T, Hayashi M, Fujita T, et al. Response to Comment on Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway[J]. J Immunol, 2019, 203(12): 3091-3092.