Taylor Brandie D, Tang Gong, Ness Roberta B, Olsen Jørn, Hougaard David M, Skogstrand Kristin, Roberts James M, Haggerty Catherine L
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Epidemiology and Biostatistics, Texas A&M Health Science Center, College Station, TX, USA.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Pregnancy Hypertens. 2016 Jan;6(1):72-8. doi: 10.1016/j.preghy.2015.11.002. Epub 2015 Nov 10.
To determine if mid-pregnancy circulating immune biomarkers are associated with preeclampsia.
Nested case-control study of 410 preeclamptic women and 297 normotensive controls with primiparous singleton pregnancies enrolled in the Danish National Birth Cohort. The mean gestational age in our cohort is 16 weeks (range 9-26).
Preeclampsia was defined by blood pressure ⩾140/90 mmHg and proteinuria ⩾3 g/24 h. Serum immune biomarkers included interleukin (IL)-6, IL-6 receptor, IL-4, IL-4 receptor, IL-5, IL-12, IL-2, TNF-α, TNF-β, TNF-receptor, IL-1β, IL-1α, IL-8, IL-10, IFN-γ, IL-18, macrophage migration inhibitory factor, macrophage inflammatory protein, transforming growth factor-beta (TGF-β), and RANTES. Associations with preeclampsia, term preeclampsia and preterm preeclampsia were determined using two logistic regression models; (1) biomarkers were dichotomized by the limit of detection (LOD); (2) on the continuous scale, non-detectable values were imputed by LOD/2 and transformed (base 2). All models were adjusted for body mass index and smoking.
IL1β was significantly associated with a decrease in the log odds of preeclampsia (p=0.0065), term preeclampsia (p=0.0230) and preterm preeclampsia (p=0.0068). Results were similar for IL4r and preeclampsia (p=0.0383). In the dichotomized models, detectable TNF-β was significantly associated with preeclampsia (ORadj 1.6, 95% CI 1.1-2.3) and term preeclampsia (OR 1.7, 95% CI 1.1-2.5) but not preterm preeclampsia. Detectable IL6 was significantly with term preeclampsia only (OR 1.5, 95% CI 1.1-2.2).
Mid-pregnancy circulating IL1β, IL4r, IL6, and TNFβ were associated with preeclampsia. However, results were not consistent across statistical models. As the relationship is complex, future studies should explore cytokine clusters in preeclampsia risk.
确定孕中期循环免疫生物标志物是否与先兆子痫相关。
对丹麦国家出生队列中410例先兆子痫孕妇和297例血压正常的初产单胎妊娠对照进行巢式病例对照研究。我们队列中的平均孕周为16周（范围9 - 26周）。
先兆子痫定义为血压≥140/90 mmHg且蛋白尿≥3 g/24 h。血清免疫生物标志物包括白细胞介素（IL）-6、IL-6受体、IL-4、IL-4受体、IL-5、IL-12、IL-2、肿瘤坏死因子（TNF）-α、TNF-β、TNF受体、IL-1β、IL-1α、IL-8、IL-10、干扰素（IFN）-γ、IL-18、巨噬细胞移动抑制因子、巨噬细胞炎性蛋白、转化生长因子-β（TGF-β）和调节激活正常T细胞表达和分泌因子（RANTES）。使用两个逻辑回归模型确定与先兆子痫、足月先兆子痫和早产先兆子痫的关联；（1）生物标志物按检测限（LOD）进行二分；（2）在连续尺度上，未检测到的值用LOD/2估算并进行转换（以2为底）。所有模型均根据体重指数和吸烟情况进行调整。
IL1β与先兆子痫（p = 0.0065）、足月先兆子痫（p = 0.0230）和早产先兆子痫（p = 0.0068）的对数优势比降低显著相关。IL4r与先兆子痫的结果相似（p = 0.0383）。在二分模型中，可检测到的TNF-β与先兆子痫（校正比值比1.6，95%置信区间1.1 - 2.3）和足月先兆子痫（比值比1.7，95%置信区间1.1 - 2.5）显著相关，但与早产先兆子痫无关。可检测到的IL6仅与足月先兆子痫显著相关（比值比1.5，95%置信区间1.1 - 2.2）。
孕中期循环中的IL1β、IL4r、IL6和TNFβ与先兆子痫相关。然而，不同统计模型的结果并不一致。由于这种关系复杂，未来的研究应探索先兆子痫风险中的细胞因子簇。
