Detection of serum lactate dehydrogenase A and its metabolites on placental function in patients with intrahepatic cholestasis of pregnancy

Int Immunopharmacol. 2024 Dec 10:145:113739. doi: 10.1016/j.intimp.2024.113739. Online ahead of print.

Abstract

A specific liver disease during pregnancy is intrahepatic cholestasis of pregnancy (ICP). The current clinical diagnosis mainly depends on the level of serum total bile acid (TBA), which lacks sensitivity and specificity. Lactate dehydrogenase A (LDHA) is a new biomarker highly expressed in the serum of ICP patients, which was screened by data-independent acquisition (DIA) proteomic technology in our previous studies. There is currently a lack of a rapid, quantitative, and sensitive detection method to measure LDHA levels in serum. This study aimed to establish a time-resolved fluorescent nanomicrospheres immunochromatographic test strip to detect LDHA in serum and evaluate its value in clinical diagnosis and treatment of ICP. Subsequently, the mechanism of LDHA in mediating the inflammatory of ICP was explored in vitro. In vitro, taurocholic acid (TCA) at a concentration of 100 μM was used to simulate an ICP environment. The AKT/mTOR/HIF-1α signaling pathway was activated in TCA-treated HTR-8/SVeno cells, leading to an increase in LDHA levels. The lactic acid produced by LDHA-mediated glycolytic metabolism may be related to the regulation of inflammation in placental trophoblast cells. According to these findings, LDHA could be a new target that provide promising ideas for the diagnosis, prediction and treatment of ICP.

Keywords: AKT/mTOR/HIF-1α; Inflammatory response; Intrahepatic cholestasis of pregnancy; Lactate dehydrogenase A; Time-resolved fluorescent nanomicrosphere.