Clinical Introduction of Lysophosphatidic Acid (LPA) and Autotaxin Assays

Abstract

The lysophospholipid mediator lysophosphatidic acid (LPA) has been shown to elicit a variety of (patho) physiological responses through specific cell-surface G protein-coupled receptors, which are now considered as promising targets for therapeutic purposes. On the other hand, determination of their concentrations in human samples, especially plasma, is clinically relevant and important for diagnostic purposes since these lysophospholipids mainly act extracellularly. LPA is predominantly and continuously produced in blood from lysophosphatidylcholine (LPC) through the plasma lysophospholipase D (lysoPLD) activity of autotaxin (ATX). Since the enzyme lysoPLD/ATX and its substrate LPC co-exist in the plasma, the level of plasma LPA changes easily in vitro after venepuncture. Laboratory testing of LPA for clinical purposes can be conducted reliably only when the samples are prepared under stringent conditions. Although it is postulated that LPA undergoes extensive dephosphorylation in vivo due to the action of lipid phosphate phosphatase, multiple regression analysis showed a strong positive correlation between the plasma LPA concentration and serum lysoPLD/ATX level. Since the serum ATX antigen level is stable, i.e., the preparation of clinical samples for this ATX measurement is easy and since its level is closely correlated to the plasma LPA concentration, the ATX assay seems to be promising for laboratory testing. In fact, the ATX level is significantly increased in several disorders, including chronic liver diseases and malignant lymphoma. The clinical significance of the LPA and lysoPLD/ATX assays will be discussed.