Serum HtrA1 is differentially regulated between early-onset and late-onset preeclampsia

Abstract

Introduction: HtrA1 (high temperature requirement A1) is a serine protease of the HtrA family. We have previously shown that the placenta expresses the highest level of HtrA1 mRNA compared to other tissues in the human. Others have reported that placental HtrA1 is significantly up-regulated in preeclampsia (PE), a pregnancy-specific multi-systemic disorder associated with new onset hypertension and proteinuria. However, it is unclear how serum HtrA1 changes in a normal pregnancy and whether it is altered in PE pregnancies.

Methods: A sandwich ELISA highly specific to human HtrA1 and suitable for serum detection was developed and thoroughly validated. This assay was then applied to serum samples from different stages of normal pregnancy, as well as early-onset (<34 weeks) and late-onset (>34 weeks) PE pregnancies.

Results: Serum HtrA1 increased progressively with increasing gestation in normal pregnancies. However, this trend was perturbed in women with PE. Compared to respective gestation-age-matched normal pregnancies, HtrA1 serum levels were significantly increased in early-onset PE, but significantly reduced in late-onset PE.

Discussion: This is the first report to show a clear increase of HtrA1 in the maternal circulation during normal pregnancy, consistent with HtrA1 being highly expressed in the placenta. Importantly, this study identified that serum HtrA1 was altered differently in early-onset and late-onset PE pregnancies, highlighting the complex regulation of HtrA1 in the different subtypes. The significant increase of serum HtrA1 in early-onset PE suggests that it may be a potential biomarker for the diagnosis of early-onset PE at disease presentation.

Keywords: Enzyme linked immunosorbent assay; HtrA1; Preeclampsia; Pregnancy; Serine protease.