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Background: Autotaxin (ATX) is a secreted enzyme that converts lysophosphatidylcholine to lysophosphatidic acid, a potent bioactive lipid mediator, through its lysophospholipase D activity. Although five alternative splicing isoforms of ATX have been identified as ATXα, ATXβ, ATXγ, ATXδ, and ATXε and the expression patterns of each isoform differ among several tissues, the clinical significance of each isoform remains to be elucidated. Methods: Anti-ATXβ and anti-ATXδ monoclonal antibodies were produced by immunization with recombinant human ATXβ and ATXδ expressed using a baculovirus system, respectively. We then developed enzyme immunoassays to measure the serum concentrations of “classical ATX” (ATXα, ATXβ, and ATXγ) and “novel ATX” (ATXδ and ATXε) antigens and evaluated the usefulness of these assays using human serum samples. Results: The with-run and between-run precision, interference, detection limit, and linearity studies for the present assay were well validated. In healthy subjects, the serum concentrations of classical ATX and novel ATX were significantly (P < 0.01) higher in women than in men, while the ratios of classical ATX or novel ATX to total ATX were not different between women and men. The concentrations of both classical ATX and novel ATX in normal pregnant subjects and patients with chronic liver diseases or follicular lymphoma were significantly higher than those in healthy subjects, while the ratio of both ATX isoforms to total ATX did not vary among these groups. Conclusions: We have developed a new enzyme immunoassay to determine the concentrations of classical ATX and novel ATX in human serum. These assays may be helpful for elucidating the distinct functional roles of each ATX isoform, which are largely unknown at present. [ABSTRACT FROM AUTHOR]

Abstract: Background: The bioactive lipid lysophosphatidic acid (LPA) exerts multiple effects in the female reproductive system. Serum/plasma LPA is mainly produced by the lysophospholipase D activity of autotaxin (ATX). Previous studies have suggested that ATX has critical roles in cancer, reproduction, and vascular development. In the present study, we evaluated the usefulness of serum ATX measurements in pregnant women. Methods: We measured the serum ATX antigen levels in 32 normal pregnant women, 15 patients with pregnancy-induced hypertension (PIH), and 7 patients with preterm delivery using a recently developed automated enzyme immunoassay. Results: The serum ATX antigen levels in normal pregnant women were significantly higher than those in non-pregnant women (P <0.001). The serum ATX antigen levels in normal pregnant women were significantly and positively correlated with the gestational week (r=0.809, P <0.001). During the third trimester, the serum ATX antigen levels of the patients with PIH (3.299±1.720mg/l) were significantly lower than those of the normal pregnant women (4.915±2.323mg/l) (P =0.04). Conclusions: The serum ATX antigen level increases with the progression of pregnancy. The serum ATX level may be a serological marker for the prediction of PIH. [Copyright &y& Elsevier]

Autotaxin (ATX) is a tumour cell motility-stimulating factor originally isolated from melanoma cell supernatants. ATX is identical to lysophospholipase D, which produces a bioactive lipid mediator, lysophosphatidic acid (LPA), from lysophosphatidylcholine. ATX is overexpressed in various malignancies, including Hodgkin lymphoma, and ATX may stimulate tumour progression via LPA production. The present study measured the serum ATX antigen levels in patients with haematological malignancies using a recently developed automated enzyme immunoassay. The serum ATX antigen levels in patients with B-cell neoplasms, especially follicular lymphoma (FL), were higher than those in healthy subjects. Serum ATX antigen levels in FL patients were associated with tumour burden and changed in parallel with the patients’ clinical courses. The serum ATX antigen levels were little affected by inflammation, unlike the soluble interleukin-2 receptor and β2-microglobulin levels. As expected, the plasma LPA levels in FL patients were correlated with the serum ATX antigen levels. Given that leukaemic tumour cells from FL patients expressed ATX, the shedding of ATX from lymphoma cells probably leads to the elevation of serum ATX antigen levels. Our results suggest that the serum ATX antigen level may be a promising and novel marker for FL. [ABSTRACT FROM AUTHOR]

Abstract: Background: Autotaxin (ATX), a tumor cell motility-stimulating factor, regulates the blood concentrations of lysophosphatidic acid (LPA), an important and multi-functional bioactive lipid, through its lysophospholipase D activity (lysoPLD). The introduction of ATX measurements into clinical laboratory testing is urgently needed. Methods: Anti-human ATX monoclonal antibodies were produced by immunization of recombinant human ATX expressed in a baculovirus system. An immunoassay for the quantitative determination of ATX was established, and human serum samples were assayed. Results: The within-run and between-run precision, interference, detection limit, and linearity studies were satisfactory. The central 95 percentile reference interval for the serum ATX antigen concentration in healthy subjects was 0.468–1.134 mg/l (n =120) and was strongly correlated with the serum lysoPLD activity. The ATX concentration was significantly (p <0.001) higher in women (0.625–1.323 mg/l) than in men (0.438–0.914 mg/l). The serum ATX concentrations were increased in patients with chronic liver diseases and decreased in postoperative prostate cancer patients but were not altered in nephrosis patients. Thus, serum ATX antigen concentrations could be used to discriminate these hypoalbuminemia conditions. Conclusions: The present ATX antigen assay may be useful for clinical laboratory testing. [Copyright &y& Elsevier]