Autotaxin Levels Research Articles

Impact of serum autotaxin level correlating with histological findings in biliary atresia

PurposePortoenterostomy is the standard treatment for biliary atresia (BA) that reduces jaundice in two thirds of cases. However, progressive liver fibrosis is common, leading to cirrhosis in most patients. Autotaxin is a new marker for the progression of hepatic fibrosis. We examined the relationship between serum autotaxin levels and liver histological findings in patients with BA. MethodsBA patients with native livers were identified in our hospital. Patients underwent protocol liver biopsies every 1 to 5 years, and liver fibrosis was evaluated based on the METAVIR score. Serum autotaxin levels were compared with the last available pathological findings. ResultsThirty-five patients were included and the median age was 10.6 years. Serum autotaxin levels was median 1.6 mg/L. The mean autotaxin level was 1.08 mg/L in F0, 1.07 mg/L in F1, 0.95 mg/L in F2, 2.17 mg/L in F3, and 2.50 mg/L in F4; it was significantly higher in F4 than in F0–F2 (P<0.0024). For predicting cirrhosis (F4) and advanced liver fibrosis (≥F3), autotaxin had the almost same areas under the curve (AUCs 0.78 and 0.90, respectively) as well as M2BPGi. ConclusionAutotaxin levels could be used to evaluate the status of native liver fibrosis.

Role of inflammation, autotaxin and lipoprotein (a) in degenerative aortic valve stenosis in patients with coronary artery disease

Aim. To study the relationship between the concentration of lipoprotein (a) (Lp (a)) and autotaxin (ATX) in patients with and without degenerative aortic valve stenosis (AoS) in the presence of coronary artery disease (CAD).Material and methods. The study included 461 patients (mean age, 66±11 years, men, 323), 354 of whom had CAD with stenosis ≥50% in at least one coronary artery according to angiography. Degenerative AoS was diagnosed with ultrasound. The control group consisted of 107 patients without CAD and degenerative AoS. Concentrations of Lp (a), ATX, lipids and blood cells were measured for all patients.Results. CAD without degenerative AoS (group 1) was diagnosed in 307 patients, while 47 patients had CAD and degenerative AoS (group 2). Patients in both groups were older than patients in the control group (66±10, 74±8, and 61±13 years, respectively). The ATX level was lower in group 1 (median [25; 75%]: 495 [406; 583] ng/ml) than in the control group (545 [412; 654] ng/ml) or group 2 (545 [476; 605] ng/ml) (p&lt;0,05 for all). Lp (a) was lower in the control group (14,5 [5,5; 36,0] mg/dl) than in group 1 (24,9 [9,7; 58,4] mg/dl) (p&lt;0,005) and group 2 (23,8 [9,9; 75,7] mg/dL) (p&lt;0,05). According to the logistic regression, an increased ATX level, regardless of age and other risk factors, was associated with degenerative AoS only in patients with CAD, while age and neutrophil to lymphocyte ratio were associated with the development of degenerative AoS both in patients with CAD and the general group.Conclusion. An elevated Lp (a) level is associated with CAD regardless of the aortic valve involvement, while an increased concentration of ATX and neutrophil to lymphocyte ratio in patients with CAD were associated with degenerative AoS regardless of age and other risk factors.

Autotaxin as a Marker for Liver Fibrosis in Chronic HCV Patients

ABSTRACT: Background: Chronic hepatitis C is a major health problem. Noninvasive markers were developed to overcome liver biopsy complications. Autotaxin (ATX) is a lysophospholipase D enzyme that regulates lysophosphatidic acid (LPA) blood concentrations. Studies have suggested that the phenotypic changes during liver fibrosis may lead to changes in ATX level in the serum. Objectives: to determine the serum Autotaxin levels and its correlation to the liver fibrosis and whether it can be used as a non-invasive diagnostic biomarker of fibrosis in Egyptian Chronic viral hepatitis C individuals. Methodology: This study was conducted on 40 patients divided into 2 groups: Group I comprised of 20 patients with chronic viral hepatitis C patients in compensated stage and Group II comprised of 20 patients with chronic viral hepatitis C patients in decompensated stage together with 20 apparently healthy controls group. All patients were subjected to the following: complete history taking، complete clinical examination، routine lab investigations، abdominal ultrasound and measurement of serum ATX level detected by ELISA technique. Results: 40 patients were enrolled. Serum ATX was significantly higher according to liver fibrosis worsen stage (p=0.002) ،ATX was significantly higher in decompensated chronic hepatitis C patients (CHC) compared to patients with compensated CHC and controls with mean values (646.7 ± 247.4) ، (615.3 ± 266) and (469.9 ± 62.3) ng/ml respectively (p=0.005). Conclusion: Autotaxin was shown to be a potential serum marker for estimating the degree of fibrosis in patients with chronic HCV.

Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

BackgroundPancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9.MethodsATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94).ResultsSerum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012).ConclusionMeasurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

Aqueous autotaxin and TGF-\u03b2s are promising diagnostic biomarkers for distinguishing open-angle glaucoma subtypes

The purpose of this study is to examine if aqueous autotaxin (ATX) and TGF-β levels could be used for differentiating glaucoma subtypes. This prospective observational study was performed using aqueous humor samples obtained from 281 consecutive patients. Open angle glaucoma patients were classified into three groups: primary open-angle glaucoma (POAG), secondary open-angle glaucoma (SOAG), and exfoliation glaucoma (XFG). Aqueous levels of ATX and TGF-βs were quantified. The AUC as well as sensitivity and specificity for the classification into normal and glaucoma subtypes using four indicators-ATX, TGF-β1, TGF-β2, and TGF-β3, upon the application of three machine learning methods. ATX, TGF-β1, and TGF-β3 were positively correlated with IOP, and ATX was significantly and negatively correlated with the mean deviation. From least absolute shrinkage and selection operator regression analysis, the AUC values to distinguish each subgroup [normal, POAG, SOAG, and XFG] ranged between 0.675 (POAG vs. normal) and 0.966 (XFG vs. normal), when four variables were used. High AUC values were obtained with ATX for discriminating XFG from normal eyes and with TGF-β3 for discriminating XFG from normal eyes, POAG, or SOAG. Aqueous TGF-β and ATX exhibited high diagnostic performance in detecting glaucoma subtypes, and could be promising biomarkers for glaucoma.

The Correlation Between the Autotaxin Enzyme and Pruritus in Egyptian Patients Suffering from Chronic Liver Disease

Pruritus associated with liver diseases confines daily activities and causes sleep deprivation in patients with chronic liver diseases. Autotoxin enzyme (ATX) was found to be higher in sera of patients with intrahepatic cholestasis and it was found to be associated with the intensity of itching. The aim of this study was to assess the correlation between the autotaxin enzyme and pruritus in Egyptian patients suffering from chronic liver disease (CLD). This cross-sectional study was carried on a total number of 80 patients with chronic liver disease divided into four groups: Group A and B included cirrhotic patients suffering from pruritis with and without cholestasis, while group C and D included patients without pruritis with or without cholestasis and group E included 17 healthy controls. They were subjected to measurement of serum autotoxin concentration by ELISA in addition to routine investigations including liver function tests: Total and direct bilirubin, ALT, AST, Alkaline phosphatase, Gama- glutamyl transferase, and serum albumin. There was a significant increase in autotaxin in the four groups included chronic liver disease patients (P-value <0.001*) compared to control group (group E). Autotoxin level was the only marker that had a significant increase in pruritus groups (groups A & B) compared to non-pruritus groups (groups C & D) with cut off value ≥ 32. Serum autotaxin level was elevated in patients with chronic liver diseases with pruritus. Autotaxin enzyme may play a key role in the induction of hepatogenic pruritus. So, autotaxin enzyme inhibitors and lysophosphatidic acid (LPA) receptor blockers could be a future line of treatment of hepatogenic pruritus.

Effect of postoperative corticosteroids on surgical outcome and aqueous autotaxin following combined cataract and microhook ab interno trabeculotomy

To evaluate the effect of postoperative corticosteroids on surgical outcome and autotaxin (ATX) levels after microhook ab interno trabeculotomy combined with cataract surgery (μLOT-CS), prospective, consecutive non-randomized case series comparing outcomes of 30 eyes with primary open angle glaucoma was performed. The aqueous ATX, intraocular pressure (IOP) and glaucoma medications were monitored for 3 months postoperatively. An in-vivo mouse μLOT model was generated. In vitro, ATX and fibrotic changes induced by dexamethasone (Dex) treatment following scratch (S) in cultured human trabecular meshwork (hTM) cells were assessed by immunofluorescence, immunoenzymatic assay, and RT-qPCR. Postoperative ATX at 1 week and the number of antiglaucoma medications at 3 months were significantly lower in non-steroid group, and steroid use was the only variable significantly associated with postoperative medications at 3 months in multiregression analyses. In vitro, ATX activity was significantly upregulated in the Dex + S group, and αSMA was significantly upregulated in the Dex and Dex + S groups. Fibronectin and COL1A1 were significantly upregulated in the S group. μLOT-CS decreased IOP and medications in the overall cohort, and non-use of postoperative steroids resulted in a smaller number of postoperative medications. Limiting postoperative steroids in μLOT may minimize IOP elevation and postoperative fibrosis.

Higher serum levels of autotaxin and phosphatidylserine-specific phospholipase A1 in patients with lupus nephritis.

Recent studies revealed that lysophospholipids (LPLs) and related molecules, such as autotaxin (ATX) and phosphatidylserine-specific phospholipase A1 (PS-PLA1 ), are candidates for novel biomarkers in melanoma, glaucoma and diabetic nephropathy. However, it is not clear whether serum levels of ATX/ PS-PLA1 would be associated with pathological and clinical findings of lupus nephritis (LN). In this retrospective cohort study, serum samples were collected from 39 patients with LN and 37 patients with other glomerular diseases. The serum levels of ATX and PS-PLA1 were evaluated for an association with renal pathology and clinical phenotypes of LN. The serum levels of ATX and PS-PLA1 were higher in the patients with LN as compared to those with other glomerular diseases. Among the classes of LN, the patients with class IV showed the trend of lower serum levels of ATX. Moreover, the patients with lower levels of ATX exhibited higher scores of activity index (AI) and chronicity index (CI). The level of ATX tended to be negatively correlated with AI and CI. These results might be explained by the effect of treatment, because the serum levels of ATX and PS-PLA1 were inversely correlated with the daily amount of oral prednisolone. Moreover, they did not reflect the level of proteinuria or kidney survival in LN patients. Although the serum levels of ATX and PS-PLA1 were affected by the treatment, these levels were higher in the patients with LN. The potential clinical benefits of these markers need to be clarified in further studies.

The impact of achieving a sustained virological response with direct-acting antivirals on serum autotaxin levels in chronic hepatitis C patients

BackgroundAutotaxin (ATX) is an emerging biomarker for liver fibrosis. Achievement of sustained virological response (SVR) by direct-acting antivirals (DAAs) results in hepatic fibrosis regression in chronic hepatitis C (CHC) patients. In this context, the clinical implications of ATX have not yet been well-defined. In this study, we aimed to assess the impact of achieving SVR with DAA therapy on serum ATX levels and whether these levels can reflect the regression of hepatic fibrosis in CHC patients. We evaluated serum ATX levels at baseline and 12 weeks post-DAA therapy in 48 CHC patients. We compared ATX with FIB4 score and AST-to-Platelet Ratio Index (APRI) as regards the detection of grade F3–4 fibrosis.ResultsSerum ATX levels were significantly declined in 47 patients after the achievement of SVR12 (p < 0.001). The diagnostic ability of ATX for the detection of grade F3–4 fibrosis was inferior to FIB4 and APRI scores at baseline and SVR12.ConclusionAchievement of SVR with DAA therapy causes a significant decline in serum autotaxin concentrations, suggesting early regression of hepatic fibrosis in CHC patients. However, its diagnostic capability for routine patient monitoring and follow-up is still under debate.

Relationship between pruritus and autotaxin in intrahepatic cholestasis of pregnancy

ObjectiveIntrahepatic cholestasis of pregnancy is a temporary, pregnancy-specific disease that resolves with delivery, characterized by itching (pruritus), as well as high transaminase and serum bile acid levels in the third trimester of pregnancy. Due to the effects of Autotaxin on the physiology of pregnancy, we aimed to investigate Autotaxin activity in patients with intrahepatic cholestasis of pregnancy. Patients and methodsSixty-nine patients diagnosed with intrahepatic cholestasis of pregnancy and 20 healthy pregnant women were enrolled in the study. Fasting serum bile acid, pruritus intensity, serum parameters, gestational week of the patients at the time of diagnosis were recorded, and birth week and birth weight were monitored. Autotaxin serum level was measured enzymatically. ResultsThe mean serum bile acid level (n=69; 38.74±35.92μmol/L) in patients with intrahepatic cholestasis of pregnancy (n=69) was detected to be higher than healthy pregnant women (n=20; 5.05±1.88μmol/L) (p<0.001). Weak correlation was detected between serum bile acid level and itch intensity (p=0.014, r=0.295), while no relation was detected between Autotaxin and itch intensity (p=0.446, r=0.09). Although mean Autotaxin (intrahepatic cholestasis of pregnancy: 678.10±424.42pg/mL, control: 535.16±256.47pg/mL) levels were high in patients with intrahepatic cholestasis of pregnancy, it was not statistically significant (p=0.157). ConclusionIn our study, we observed that the serum Autotaxin level did not make a significant difference in patients with intrahepatic cholestasis of pregnancy compared to healthy pregnant women. These findings suggest that larger clinical studies are required to reveal the physio-pathological effects of Autotaxin on pregnancy.

Serum autotaxin levels in responders to HCV treatment by direct-acting antivirals

BackgroundHepatitis C virus (HCV) infection is considered one of the main causes of chronic liver disease around the world. Liver biopsy has been believed to be the gold standard for the assessment of the degree of liver fibrosis. Thus, there is a need to improve non-invasive evaluation of liver fibrosis. The aim of the present study was to study the changes in serum levels of ATX (Autotaxin) as a marker of hepatic fibrosis in responders to HCV treatment by DAAs. This prospective study was carried out at hepatology outpatient clinics for HCV treatment in Mansoura Specialized Medical Hospital that involved 54 participants: 34 patients with HCV and 20 controls; ATX was measured for the controls and all patients before and after treatment.ResultsWe found a significant higher ATX level in control subjects vs HCV patients, 100% of control subjects had ATX > 97.5 and 58.8% of HCV had ATX ≤ 97.5. Also, a significantly higher ATX after treatment with DAAs as a whole was observed.ConclusionThe authors concluded that ATX should be considered cautiously as a diagnostic marker for liver fibrosis in Egyptian patients with chronic hepatitis C infection. Although this study yielded negative results, this may be important to prevent duplication of the research efforts.

Autotaxin: An Early Warning Biomarker for Acute-on-chronic Liver Failure.

Background and Aims: Recent accumulating evidence indicates the biological actions of autotaxin (ATX) in liver disease. However, the relationship between ATX and liver failure has not been reported. The present study aimed to examine alterations of serum ATX in acute-on-chronic liver failure (ACLF) and evaluate whether serum ATX could be useful as an early warning biomarker of ACLF.Methods: Serum ATX was measured in 50 patients with hepatitis B-related ACLF, 14 patients with alcohol-related ACLF, 11 patients with hepatitis B-related pre-ACLF, 11 patients with alcohol-related Child-Pugh A cirrhosis, 39 patients with hepatitis B-related Child-Pugh A cirrhosis, 26 patients with chronic hepatitis B, and 38 healthy volunteers by enzyme-linked immunosorbent assay.Results: Serum ATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group; furthermore, patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF. Serum ATX levels were significantly higher among male ACLF patients with preclinical infection, spontaneous bacterial peritonitis or pneumonia, as compared to patients with ACLF but no spontaneous bacterial peritonitis or pneumonia. Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score. Serum ATX ≥ 584.1 ng/mL was a poor prognostic factor for ACLF (hazard ratio of 4.750, 95% confidence interval of 1.106-20.392, p=0.036).Conclusions: Serum ATX level may be a useful early warning biomarker for ACLF.

Post-Treatment M2BPGi Level and the Rate of Autotaxin Reduction are Predictive of Hepatocellular Carcinoma Development after Antiviral Therapy in Patients with Chronic Hepatitis C.

Patients with chronic hepatitis C virus (HCV) develop hepatocellular carcinoma (HCC) regardless of achieving a sustained viral response (SVR). Because advanced liver fibrosis is a powerful risk factor for HCC, we analyzed the association between autotaxin (ATX), a liver fibrosis marker, and post-SVR HCC development within 3 years after antiviral treatment. We included 670 patients with HCV who received direct-acting antivirals, achieved SVR and were followed up for at least 6 months (270 of them were followed up for 3 years or more). We measured serum ATX levels before treatment and 12/24 weeks after treatment. The diagnosis of HCC was based on imaging modalities, such as dynamic computed tomography and dynamic magnetic resonance imaging and/or liver biopsy. The present study revealed that high levels of serum ATX predicted post-SVR HCC development (area under the receiver operating characteristic: 0.70–0.76). However, Wisteria floribunda agglutinin positive Mac-2 binding protein (M2BPGi), another liver fibrosis marker, was a more useful predictive marker especially post-treatment according to a multivariate analysis. Patients with a high rate of ATX reduction before and after antiviral treatment did not develop HCC regardless of high pretreatment ATX levels. In conclusion, post-treatment M2BPGi level and the combination of pretreatment ATX levels and rate of ATX reduction were useful predictive markers for post-SVR HCC development in patients with chronic HCV infection.

Microglial lysophosphatidic acid promotes glioblastoma proliferation and migration via LPA1 receptor.

Glioblastomas (GBMs) are highly aggressive primary brain tumors characterized by cellular heterogeneity, insensitivity to chemotherapy and poor patient survival. Lysophosphatidic acid (LPA) is a lysophospholipid that acts as a bioactive signaling molecule and plays important roles in diverse biological events during development and disease, including several cancer types. Microglial cells, the resident macrophages of the central nervous system, express high levels of Autotaxin (ATX,Enpp2), an enzyme that synthetizes LPA. Our study aimed to investigate the role of LPA on tumor growth and invasion in the context of microglia-GBM interaction. First, through bioinformatics studies, patient data analysis demonstrated that more aggressive GBM expressed higher levels of ENPP2, which was also associated with worse patient prognosis with proneural GBM. Using GBM-microglia co-culture system we then demonstrated that GBM secreted factors were able to increase LPA1 and ATX in microglia, which could be further enhanced by hypoxia. On the other hand, interaction with microglial cells also increased ATX expression in GBM. Furthermore, microglial-induced GBM proliferation and migration could be inhibited by pharmacological inhibition of LPA1 , suggesting that microglial-derived LPA could support tumor growth and invasion. Finally, increased LPA1 expression was observed in GBM comparing with other gliomas and could be also associated with worse patient survival. These results show for the first time a microglia-GBM interaction through the LPA pathway with relevant implications for tumor progression. A better understanding of this interaction can lead to the development of new therapeutic strategies setting LPA as a potential target for GBM treatment.

Association of serum autotaxin levels with liver fibrosis in patients pretreatment and posttreatment with chronic hepatitis C.

The evaluation of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection is important as it is a risk factor for hepatocellular carcinoma. In the recent years, autotaxin (ATX) has been established as a new noninvasive biomarker to predict liver fibrosis. However, antiviral treatment has been reported to decrease serum ATX, but it is unclear whether posttreatment ATX levels reflect liver fibrosis. In the present study, the correlation between ATX and liver fibrosis in pretreatment and posttreatment patients with HCV infection was analyzed. A total of 199 samples from 136 patients with HCV infection who had undergone hepatic biopsy before and/or after antiviral treatment at Osaka City University Hospital were used. Posttreatment patients included 38 interferon-treated patients and 80 interferon-free direct-acting antiviral-treated patients; all patients achieved a sustained virological response (SVR). Serum ATX levels were determined by enzyme immunoassay with an AIA-2000 analyzer. Serum ATX levels were largely correlated with liver fibrosis stage in patients with HCV infection before and after antiviral treatment. The measured values decreased even in similar liver fibrosis stages after treatment. The area under the receiver operating characteristic curve for the ability of ATX to diagnose above F2 stage before treatment was 0.81 (both male and female) and that after achieving SVR, it was 0.71 (male) and 0.72 (female). Serum ATX levels were correlated with histological liver fibrosis stage after achieving SVR. However, separate cutoff values before and after antiviral therapy should be established.

Clinical Usefulness of Serum Autotaxin for Early Prediction of Relapse in Male Patients with Type 1 Autoimmune Pancreatitis

Serum IgG4 level is a useful diagnostic marker for autoimmune pancreatitis (AIP), but it is difficult to use to predict relapse. We investigated whether serum autotaxin (ATX) level is predictive of AIP relapse after steroid therapy. Fifty-six patients with type 1 AIP were investigated. We measured serum ATX at the time of diagnosis. We selected 24 males for whom serum samples during steroid therapy had been obtained and measured serum ATX at steroid therapy for induction of remission and at maintenance therapy. In the relapse group, we also measured ATX at the time of relapse. ATX was significantly higher in female patients than in male patients. In order to clarify changes in ATX during steroid therapy, we focused on 24 male patients. We found that ATX decreased significantly during steroid therapy for induction of remission and at the time of maintenance therapy. In half of all patients who relapsed during maintenance therapy, ATX was significantly elevated at the time of relapse compared with that of induction therapy (P = 0.039). When we compared ATX at the time of maintenance therapy between patients with relapse and without, we observed significantly higher ATX in the former (P = 0.024). We found that the combination of ATX and elastase-1 could predict relapse with high accuracy (95%). Preliminary evidence suggests that serum ATX might serve as a candidate biomarker to predict relapse of AIP as well as to monitor the effect of steroid therapy.

Involvement of autotaxin in the pathophysiology of elevated intraocular pressure in Posner-Schlossman syndrome

To examine whether autotaxin (ATX) in the aqueous humor causes elevated intraocular pressure (IOP) in patients with Posner-Schlossman syndrome (PSS). ATX and transforming growth factor beta (TGF-β) in the aqueous humor were quantified in PSS patients. The expression of ATX and TGF-β in cytomegalovirus (CMV)-infected-human trabecular meshwork (hTM) cells was examined. Biological changes in hTM cells and monkey Schlemm’s canal endothelial (SCE) cells cultured in the conditioned medium of CMV-infected hTM cells were analyzed. The expression of ATX and TGF-β1 was upregulated in the aqueous humor of CMV-positive PSS patients, and the level of ATX in the aqueous humor was positively correlated with IOP. CMV infection upregulated ATX and TGF-β1 in hTM cells. The conditioned medium induced fibrotic changes in hTM cells and reduced SCE permeability, which was attenuated by an ATX inhibitor, a lysophosphatidic acid receptor antagonist, and a Rho kinase inhibitor. ATX in the aqueous humor induced by CMV infection may trigger elevated IOP. Modulating ATX activity may be a novel treatment modality for PSS.

Genetic deletion of Autotaxin from CD11b+ cells decreases the severity of experimental autoimmune encephalomyelitis.

Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80+ CD11b+ cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b+ cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders.

Prognostic value of serum autotaxin in liver cirrhosis and prediction of hepatocellular carcinoma

BackgroundAutotaxin is a lysophospholipase D related to liver fibrosis; its clinical role in liver cirrhosis is still unknown or limited. In this study we investigate the relation of autotaxin serum levels and prognosis of liver disease and/or prediction of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) patients.Patients and methodsThis observational, prospective case–control study included 180 participants, 60 patients with HCV-related liver cirrhosis, 60 HCV noncirrhotic patients, and 60 healthy controls. They were enrolled from inpatients and clinics of a tertiary-care hospital. Baseline characteristics, serum autotaxin, Child–Turcotte–Pugh and model of end-stage liver disease scores were determined. Abdominal ultrasound and upper gastrointestinal endoscopy were done at the beginning of the study. Cirrhotic patients were prospectively followed up for 6 months.ResultsPatients with liver cirrhosis had the highest level of autotaxin (106±24 μg/ml) compared with noncirrhotic HCV patients (81.9±21 μg/ml) and healthy controls (42.5±11 μg/ml) using one-way analysis of variance test (P=0.000). Spearman’s correlation analysis showed no significant correlation between autotaxin and Child–Turcotte–Pugh score (r=0.02; P<0.70), and model of end-stage liver disease score (r=0.15; P<0.41). At 6 months of follow-up, patients who developed HCC or encephalopathy had significantly higher baseline autotaxin level (141±55 μg/ml; P=0.02, 117±56.6 μg/ml; P=0.000), respectively, than patients who did not (102±34, 90.7±40 μg/ml). Cutoff values of autotaxin for the prediction of HCC and encephalopathy were 95 and 92μg/ml, respectively, with 91 and 92% sensitivity.ConclusionAutotaxin is a sensitive predictor for the development of HCC and encephalopathy in HCV-related cirrhotic patients. However, it was not related to disease severity.

Elevated Autotaxin and LPA Levels During Chronic Viral Hepatitis and Hepatocellular Carcinoma Associate with Systemic Immune Activation.

Circulating autotaxin (ATX) is elevated in persons with liver disease, particularly in the setting of chronic hepatitis C virus (HCV) and HCV/HIV infection. It is thought that plasma ATX levels are, in part, attributable to impaired liver clearance that is secondary to fibrotic liver disease. In a discovery data set, we identified plasma ATX to be associated with parameters of systemic immune activation during chronic HCV and HCV/HIV infection. We and others have observed a partial normalization of ATX levels within months of starting interferon-free direct-acting antiviral (DAA) HCV therapy, consistent with a non-fibrotic liver disease contribution to elevated ATX levels, or HCV-mediated hepatocyte activation. Relationships between ATX, lysophosphatidic acid (LPA) and parameters of systemic immune activation will be discussed in the context of HCV infection, age, immune health, liver health, and hepatocellular carcinoma (HCC).