Abstract
Since the clinical outcome of patients with sarcoidosis is still unpredictable, a good prognostic biomarker is necessary. Autotaxin (ATX) and phosphatidylserine-specific phospholipase A1 (PS-PLA1) function as main enzymes to produce lysophospholipids (LPLs), and these enzymes are attracting attention as useful biomarkers for several chronic inflammatory diseases. Here, we investigated the relationships between LPLs-producing enzymes and the disease activity of sarcoidosis. In total, 157 patients with sarcoidosis (active state, 51%) were consecutively enrolled. Using plasma or urine specimens, we measured the values of LPLs-producing enzymes. Urine ATX (U-ATX) levels were significantly lower in the active state compared to those in the inactive state, while the plasma ATX (P-ATX) and PS-PLA1 levels showed no significant difference between these two states. Concerning the comparison with existing clinical biomarkers for sarcoidosis, U-ATX showed a weak negative correlation to ACE, P-ATX a weak positive correlation to both ACE and sIL-2R, and PS-PLA1 a weak positive one to sIL-2R. Notably, only the U-ATX levels inversely fluctuated depending on the status of disease activity whether OCS had been used or not. These findings suggest that U-ATX is likely to be a novel and useful molecule for assessing the disease activity of sarcoidosis.
Highlights
Since the clinical outcome of patients with sarcoidosis is still unpredictable, a good prognostic biomarker is necessary
Because the present study aims to find novel clinically useful biomarkers and apply them to the daily examination in a clinical setting, we focused on the values of ATX and phosphatidylserine-specific phospholipase A1 (PS-PLA1), both of which are present in body fluids and have been used as an alternative for the value of lysophosphatidic acid (LPA) and LysoPS, respectively[27]
While the PS-PLA1 levels did not show any difference between active and inactive states in all subjects, female subjects in an active state showed a significant increase in those values compared with subjects in an inactive state (14.9 [12.3–18.9] for active state and 13.5 [11.8–16.7] ng/mL for inactive state, p = 0.049) (Fig. 1g,h,i). These findings suggest that the levels of Urine ATX (U-ATX) and PS-PLA1 are associated with the disease inactivity of sarcoidosis, especially in female subjects
Summary
Since the clinical outcome of patients with sarcoidosis is still unpredictable, a good prognostic biomarker is necessary. Autotaxin (ATX) and phosphatidylserine-specific phospholipase A1 (PS-PLA1) function as main enzymes to produce lysophospholipids (LPLs), and these enzymes are attracting attention as useful biomarkers for several chronic inflammatory diseases. Increased levels in several serum laboratory tests such as angiotensin converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R) and lysozyme were observed at the time of diagnosis These molecules seem somewhat useful for monitoring the disease activity, but not enough to estimate the changes in severity or to predict the prognosis of sarcoidosis. If we can find useful monitoring or prognostic biomarkers associated with the pathophysiology of sarcoidosis, it would be helpful for improving the management of patients with sarcoidosis, and for developing novel treatment strategies Eicosanoid mediators such as prostaglandins and leukotrienes have long been studied as first-generation bioactive lipids. Because the present study aims to find novel clinically useful biomarkers and apply them to the daily examination in a clinical setting, we focused on the values of ATX and PS-PLA1, both of which are present in body fluids and have been used as an alternative for the value of LPA and LysoPS, respectively[27]
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