Department of Laboratory, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, No.9, Jinsui Road, Guangzhou, 510623, Guangdong, China.
School of Public Health, Guangzhou Medical University, Guangzhou, 511436, China.
Reprod Biol Endocrinol. 2021 Apr 19;19(1):56. doi: 10.1186/s12958-021-00742-z.
Hypertension disorder of pregnancy (HDP) is one of the leading causes of maternal and foetal illness. The aim of the current study was to identify and verify novel serum markers for HDP.
A label-free LC-MS/MS method was used to establish the serum proteomic profiles of 12 pre-HDP (before clinical diagnosis of HDP) pregnancies and verify prioritized candidates in the verification set of 48 pre-HDP pregnancies. These biomarkers were revalidated by ELISA in an independent cohort of 88 pre-HDP pregnancies. Subsequently, the candidate biomarkers were histologically analysed by immunohistochemistry, and function was evaluated in TEV-1 cells.
We identified 33 proteins with significantly increased abundance and 14 with decreased abundance (peptide FDR ≤ 1%, P < 0.05). Complement was one of the top enriched components in the pre-HDP group compared with the control group. Three complement factors (CLU, CFHR5, and CRP) were significantly increased in the three sets, of which CLU was a critical factor for the development of HDP (OR = 1.22, P < 0.001). When these three factors and body weight were combined, the AUC was 0.74, with a sensitivity of 0.67 and specificity of 0.68 for HDP prediction compared with normal pregnancy. In addition, inflammation-induced CLU could inhibit the invasion of TEV-1 cells.
Complement proteins may play an essential role in the occurrence of HDP by acting on trophoblast cells. CLU may be a high-risk factor for HDP, and the models combining candidates show reasonable screening efficiency of HDP in the first half of pregnancy.
妊娠高血压疾病（HDP）是导致母婴疾病的主要原因之一。本研究旨在寻找和验证 HDP 的新型血清标志物。
采用无标记 LC-MS/MS 方法建立 12 例 HDP 前（临床诊断 HDP 前）妊娠的血清蛋白质组图谱，并在 48 例 HDP 前妊娠的验证集中验证优先候选者。这些生物标志物通过 ELISA 在 88 例 HDP 前妊娠的独立队列中进行重新验证。随后，通过免疫组织化学对候选生物标志物进行组织学分析，并在 TEV-1 细胞中评估其功能。
我们发现 33 种蛋白的丰度显著增加，14 种蛋白的丰度降低（肽 FDR≤1%，P<0.05）。与对照组相比，补体是 HDP 前组中富集程度最高的成分之一。CLU、CFHR5 和 CRP 三种补体因子在三组中均显著增加，其中 CLU 是 HDP 发生的关键因素（OR=1.22，P<0.001）。当将这三种因素和体重结合起来时，AUC 为 0.74，用于预测 HDP 的灵敏度为 0.67，特异性为 0.68，与正常妊娠相比。此外，炎症诱导的 CLU 可抑制 TEV-1 细胞的侵袭。
补体蛋白可能通过作用于滋养层细胞在 HDP 的发生中起重要作用。CLU 可能是 HDP 的高危因素，候选物结合模型在妊娠前半期对 HDP 具有合理的筛查效率。
