血清C1q等补体因子对子痫前期诊断及风险预测的临床应用评价

Clinical application evaluation of serum C1q and other complement factors in the diagnosis and prediction of preeclampsia

目的观察正常妊娠时不同孕期血清补体C1q、C3、C4、B因子的水平,评价血清补体C1q、C3、C4、B因子的水平对子痫前期(PE)的诊断价值以及对PE发生风险的预测价值。方法于2017年1月至2018年3月选取北京大学第三医院妇产科3组病例。(1)回顾性选取正常妊娠8~14周、20~26周、28~36周孕妇共3组,每组30例,检测其血清补体C1q、C3、C4、B因子的水平并进行比较。(2)选取PE患者115例,包括早发轻度PE 17例、早发重度PE 47例、晚发轻度PE 24例、晚发重度PE 27例和早发组、晚发组同孕期正常妊娠对照各30例,通过方差分析及两两比较,评价血清补体C1q、C3、C4、B因子对PE的诊断价值。(3)通过214例前瞻性巢式病例对照研究,评价妊娠期妇女20~26周血清C1q、B因子的水平对PE发生风险的预测作用。结果血清C1q水平在未孕及整个孕期保持稳定;C3、B因子水平在孕早期开始升高,孕中期后保持稳定;C4在孕早期升高,之后保持稳定。与对照组相比,4组PE患者血清补体C1q水平均明显降低(中位数分别为169 mg/L、161 mg/L、165 mg/L和163 mg/L;早发、晚发对照组分别为187 mg/L和194 mg/L;U值分别为130.500、426.500、159.500和130.500, P均<0.05);除早发轻度组(1275 mg/L)之外,其他3组患者的血清C3水平均较对照组明显下降(中位数分别为1 170 mg/L、1 323 mg/L和1 223 mg/L;早发、晚发对照组分别为1 438 mg/L和1 434 mg/L;U值分别为379.000、246.000和160.000,P均<0.05);早发重度和晚发重度PE患者的血清C4水平均较对照组明显下降(中位数分别为140 mg/L和142 mg/L;早发、晚发对照组分别为223 mg/L和235 mg/L;U值分别为329.500、136.500,P均<0.001);早发三组之间、晚发三组之间,血清B因子水平差异均无统计学意义(早发轻、重度组中位数分别为332 mg/L、318 mg/L,早发同孕期对照组为312 mg/L;晚发轻、重度组分别为316 mg/L、314 mg/L,晚发同孕期对照组为303 mg/L;χ2分别为5.990、1.770,P均>0.05)。214例具有PE危险因素的妊娠妇女,33例(15.4%)发展为PE。发生PE组的孕妇20~26周血清C1q、C3、C4、B因子水平与未发生PE组相比,差异无统计学意义(C1q:175 mg/L vs. 184 mg/L;C3:1 523 mg/L vs.1 467 mg/L;C4:230 mg/L vs. 229 mg/L;FB:344 mg/L vs. 320 mg/L;U值分别为2 090.000、1 575.000、2 058.500和1 362.000,P均>0.05)。发生PE组的孕妇20~26周血清C1q、C3、C4水平与同孕期健康孕妇相比,差异无统计学意义(C1q:175 mg/L vs. 190 mg/L;C3:1 523 mg/L vs. 1 428 mg/L;C4:230 mg/L vs. 227 mg/L;U值分别为353.000、395.000和493.500,P均>0.05),但血清B因子水平与同孕期健康孕妇相比,差异有统计学意义(344 mg/L vs. 306 mg/L;U值为233.500,P=0.007)。结论PE患者血清C1q水平明显降低,可作为PE诊断的潜在指标,但是孕20~26周血清C1q、C3、C4水平不能预测发生PE风险。血清B因子不能作为PE诊断的指标,但是PE患者孕20~26周的血清B因子较正常妊娠升高,提示B因子可能是一个潜在的预测指标。

Objective To observe the levels of serum complement C1q, C3, C4 and factor B in different phases during normal pregnancy; To evaluate the diagnostic value and the predictive value of serum complement C1q, C3, C4 and factor B in preeclampsia (PE).Methods Three groups of subjectes were enrolled from January 2017 to March 2018 in Department of Obstetrics and Gynecology, Peking University Third Hospital. (1) 30 pregnant women in each group at 8-14 weeks, 20-26 weeks and 28-36 weeks were retrospectively selected, and the serum levels of complement C1q, C3, C4 and B factors were measured and compared. (2)Selecting 17 cases of early-onset mild PE, 47 cases of early-onset severe PE, 24 cases of late-onset mild PE, 27 cases of late-onset severe PE, and 30 normal pregnant cases of the same gestational stage as early-onset / late-onset controls, through ANOVA analysis and comparison between two groups, this study evaluated the diagnostic value of serum complement C1q, C3, C4 and factor B in PE. (3)To evaluate the predictive effect in PE, it analyzed serum C1q and factor B levels of pregnant women at 20-26 gestation weeks through prospective nested case-control study of 214 cases.Results The levels of serum C1q remained stable in the whole pregnancy. The levels of C3 and factor B increased at the early stage of pregnancy and remained stable after the middle stage. C4 increased early in pregnancy and then remained stable. Compared with the control group, the levels of serum C1q in all four types of PE patients were significantly decreased (median: 169 mg/L, 161 mg/L, 165 mg/L, 163 mg/L; early-onset, late-onset control group: 187 mg/L, 194 mg/L; U=130.500, 426.500, 159.500, 130.500, all P<0.05). Serum C3 levels of all the other three types of PE patients were significantly lower than those of the control groups (median: 1 170 mg/L, 1 323 mg/L, 1 223 mg/L; early-onset, late-onset control groups: 1 438 mg/L, 1 434 mg/L; U= 379.000, 246.000, 160.000, all P<0.05), except for the early-onset mild PE (1 275 mg/L). Serum C4 levels of patients with early/late onset severe PE were significantly lower than those of the control groups (median: 140 mg/L, 142 mg/L; early-onset, late-onset control groups: 223 mg/L, 235 mg/L; U= 329.500, 136.500, both P<0.001). Serum factor B levels showed no statistical difference among 3 early on-set groups or among 3 late on-set groups(early-onset group median: 332 mg/L, 318 mg/L, early-onset control group 312 mg/L; late-onset group median: 316 mg/L, 314 mg/L, late-onset group 303 mg/L; χ2=5.990, 1.77, all P>0.05). 33 (15.4%) cases developed PE out of 214 pregnant women with PE risk factors. Compared to those who didn′t develop PE, it showed no statistical difference of serum C1q, C3, C4, and factor B levels at 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 184 mg/L; C3: 1 523 mg/L vs. 1 467 mg/L; C4: 230 mg/L vs. 229 mg/L; FB: 344 mg/L vs. 320 mg/L; U=2 090.000, 1 575.000, 2 058.500, 1 362.000, all P>0.05). Compared to those of the healthy pregnant controls, it showed no statistical difference of serum C1q, C3 and C4 levels of 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 190 mg/L; C3: 1 523 mg/L vs. 1 428 mg/L; C4: 230 mg/L vs. 227 mg/L; U=353.000, 395.000, 493.500, all P>0.05), while it showed statistical difference (344 mg/L vs. 306 mg/L; U= 233.500, P=0.007) for factor B.Conclusions Serum C1q level of PE patients significantly decreased, which can be used as potential indicators of PE diagnosis, but serum C1q, C3, C4 level of 20-26 gestational weeks cannot predict risk of PE. Factor B cannot serve as serum index of PE diagnosis, but its serum levels at 20-26 gestational weeks werer higher than those of normal pregnant controls, factor B may be a potential predictor, but need further verification.