目的 分析补体系统关键成分C3、C4与脓毒症患儿病情严重程度的关系,探讨补体系统活化在脓毒症进展过程中的作用,以期为严重脓毒症患儿的诊治提供参考.方法 收集2012年12月至2015年12月在南京医科大学附属儿童医院诊治的脓毒症患儿共424例,经筛选后共347例脓毒症患儿纳入研究,其中一般脓毒症169例,严重脓毒症178例.转入儿科重症监护病房(PICU) 24 h内采集血标本进行淋巴细胞免疫分型、体液免疫分析及血常规、凝血功能、肝肾功能检测.通过查阅患儿病历,收集患儿一般资料、辅助检查及临床诊治等资料.比较一般脓毒症组及严重脓毒症组以上各指标的差异.同时分析补体C3、C4与脓毒症病情严重程度的相关性及补体C3与凝血指标、肝、肾、心肌等损伤指标的相关性.运用Logistic多元回归模型分析补体C3与严重脓毒症、多器官功能障碍综合征(MODS)的关系,并采用Cox回归模型进行生存分析.结果 严重脓毒症组自然杀伤(NK)细胞百分比低于一般脓毒症组[6.6％(3.7％,10.7％)比8.5％(4.7％,13.3％),Z=2.635,P=0.008],补体C3水平低于一般脓毒症组[0.653(0.462,0.985) g/L比0.991(0.678,1.265) g/L,Z=5.684,P＜0.001],补体C4水平亦低于一般脓毒症组[0.160(0.102,0.244) g/L比0.190(0.121,0.265)g/L,Z=2.513,P =0.012].重症肺炎比例在严重脓毒症组高于一般脓毒症组(34.3％比19.5％,x2=9.540,P=O.002).严重脓毒症患儿发生肝功能损伤的比例高于一般脓毒症组(48.3％比16.0％,x2=41.28,P＜0.001),且在PICU治疗的天数也更长[10.7(6.5,17.4)d比7.5(4.0,12.4)d,Z=-4.039,P＜0.001].相比一般脓毒症患儿,补体C3在单器官功能障碍、MODS及死亡组中均明显降低,差异有统计学意义(K =33.04,P =0.001),且有随病情严重程度降低的趋势.补体C4在各组间差异无统计学意义(K=7.36,P=0.061).在凝血指标中,C3与血小板和纤维蛋白原水平降低均呈正相关(p =0.31、0.53,均P＜0.001);与国际标准化比值(INR)、活化部分凝血活酶时间均呈负相关(p=-0.39、-0.34,均P＜0.001).在器官损伤指标中,C3水平降低与肝功能损伤指标丙氨酸氨基转移酶、总胆红素水平均呈负相关(p=-0.30,-0.28,均P＜0.001),与肾功能损伤指标血肌酐水平呈负相关(p=-0.24,P ＜0.001),与心肌损伤指标肌酸激酶同工酶水平呈负相关(p=-0.27,P＜0.001).Logistic多元回归模型表明,经多因素校正后,C3降低依然是严重脓毒症(OR=3.45,P＜0.001)及MODS(OR=3.03,P=0.005)发生的风险因素,依据年龄进行分层分析表明,在＜1岁患儿组,C3降低是严重脓毒症发生的风险因素(OR =2.78,P =0.019),也是MODS发生的风险因素(OR =3.57,P=0.015);在＞1岁患儿组中,C3降低同样是发生严重脓毒症的风险因素(OR =4.76,P =0.008).在无肝功能损伤患儿中,C3降低依然是发生严重脓毒症(OR =4.17,P =0.002)及MODS(OR=9.09,P=0.002)的风险因素.Cox回归分析表明,补体C3降低是脓毒症患儿28 d死亡的危险因素(HR=3.57,P=0.026).结论 补体C3水平降低与脓毒症患儿凝血障碍指标、器官损伤指标存在相关性,是脓毒症患儿进展为严重脓毒症、MODS和死亡的危险因素,可用于评估脓毒症患儿病情及预后.%Objective To analyze the relationship between complement key component C3,C4 and the severity of sepsis in children,in order to explore the role of complement activation in the progression of sepsis and provide a reference for diagnosis and treatment of severe sepsis.Methods Four hundred and twenty-four children diagnosed as sepsis from December 2012 to December 2015 in Children's Hospital of Nanjing Medical University were enrolled in this study,among whom 347 children with sepsis were eligible for the following research including 169 cases of common sepsis and 178 cases of severe sepsis.Blood specimens were collected in 24 hours after their admission into pediatric intensive care unit(PICU) for the analysis of lymphocyte subsets,humoral immunity,blood routine analysis,coagulation,liver and renal function analysis.General information was collected by consulting their medical records,laboratory analysis and clinical treatment.The relationship between complement C3,C4 and the severity of sepsis was analyzed,and the correlation between C3 and coagulation,liver,renal,myocardium damage was also studied.Logistic regression was used to analyze the relationship between C3 and the progression to severe sepsis and multiple organ dysfunction syndrome(MODS),while Cox regression was used for survival analysis.Results Natural killer(NK) cell percentage was lower in severe sepsis group than that in common sepsis group [6.6％ (3.7％,10.7％) vs.8.5％ (4.7％,13.3％),Z =2.635,P =0.008],while C3 decreased in severe sepsis group compared with common sepsis group [0.653 (0.462,0.985) g/L vs.0.991 (0.678,1.265) g/L,Z =5.684,P ＜ 0.001],and C4 decreased in severe sepsis group compared with common sepsis group [0.160(0.102,0.244) g/L vs.0.190(0.121,0.265) g/L,Z =2.513,P =0.012].The proportion of severe pneumonia was higher in severe sepsis group than that in common sepsis group (34.3％ vs.19.5％,x2 =9.540,P =0.002),and liver function damage proportion was increased in severe sepsis group than that in common sepsis group (48.3％ vs.16.0％,x2 =41.28,P ＜0.001),and the duration of PICU treatment was longer in severe sepsis group than that in common sepsis group[10.7(6.5,17.4) d vs.7.5(4.0,12.4) d,Z =-4.039,P ＜0.001].C3 was significantly decreased in children with single organ dysfunction,multiple organ dysfunction and death group compared with common sepsis group (K =33.04,P =0.001),and the median of each group decreased with the severity of sepsis,but C4 had no difference among 4 groups (K =7.36,P =0.061).C3 was positively correlated with coagulation marker platelet (p =0.31,P ＜ 0.001) and fibrinogen (ρ =0.53,P ＜ 0.001),but negatively correlated with international normalized ratio (INR) (ρ =-0.39,P ＜ 0.001) and activated partial thromboplastin time (p =-0.34,P ＜ 0.001).C3 was also negatively correlated with liver damage marker alanine transaminase (ρ =-0.30,P ＜ 0.001) and total bilirubin (ρ =-0.28,P ＜ 0.001),and had a negative correlation with renal function marker creatinine (p =-0.24,P ＜ 0.001) and myocardial damage marker creatine kinase-MB (p =-0.27,P ＜ 0.001).The depletion of C3 was a risk factor of severe sepsis(OR =3.45,P ＜ 0.001) and MODS(OR =3.03,P =0.005) after being adjusted for confounding factors by using Logistic regression.In stratification analysis,C3 depletion was still a risk factor of severe sepsis (OR =2.78,P =0.019) and MODS (OR =3.57,P =0.015) among children less than 1 year old,and was also a risk factor of severe sepsis(OR =4.76,P =0.008) among children more than 1 year old as well.In children without liver function damage,C3 depletion was still a risk factor of severe sepsis(OR =4.17,P =0.002) and MODS(OR =9.09,P =0.002).Cox regression showed that C3 depletion was a hazard in 28-day mortality (HR =3.57,P =0.026) in children with sepsis.Conclusion The decrease of C3 is correlated with coagulation dysfunction and organ damage marker,while C3 depletion was a risk factor of severe sepsis,MODS and 28-day mortality,and could be a potential prognostic marker of children with sepsis.
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