Dataset Information

Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis.

ABSTRACT: Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology and characterized by continuing hepatocellular inflammation and necrosis. Autoantibodies represent accessible markers to measure the adaptive immune responses in the clinical investigation. Protein microarrays have become an important tool to discriminate the disease state from control groups, even though there is no agreed-upon standard to analyze the results.In the present study 15 sera of patients with AIH and 78 healthy donors (HD) have been tested against 1626 proteins by an in house-developed array. Using a Partial Least Squares Discriminant Analysis (PLS-DA) the resulting data interpretation led to the identification of both new and previously identified proteins. Two new proteins AHPA9419 and Chondroadherin precursor (UNQ9419 and CHAD, respectively), and previously identified candidates as well, have been confirmed in a validation phase by DELFIA assay using a new cohort of AIH patients. A receiver operating characteristic analysis was used for the evaluation of biomarker candidates. The sensitivity of each autoantigen in AIH ranged from 65 to 88%; moreover, when the combination of the two new autoantigens was analyzed, the sensitivity increased to 95%.Our findings demonstrate that the detection of autoantibodies against the two autoantigens could improve the performance in discriminating AIH patients from control classes and in combination with previously identified autoantigens and they could be used in diagnostic/prognostic markers.

SUBMITTER: Mazzara S

PROVIDER: S-EPMC4573979 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis.

Mazzara Saveria S Sinisi Antonia A Cardaci Angela A Rossi Riccardo Lorenzo RL Muratori Luigi L Abrignani Sergio S Bombaci Mauro M

PloS one 20150916 9

<h4>Background</h4>Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology and characterized by continuing hepatocellular inflammation and necrosis. Autoantibodies represent accessible markers to measure the adaptive immune responses in the clinical investigation. Protein microarrays have become an important tool to discriminate the disease state from control groups, even though there is no agreed-upon standard to analyze the results.<h4>Results</h4>In the present study 15 ser ...[more]

PMID: 26375394

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Project description:Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver damage progresses to cirrhosis or hepatocellular carcinoma (HCC). The mainstay therapy for AIH is steroids and other immunosuppressive treatments. Currently, there are no validated markers for monitoring immune-mediated hepatic inflammation. Galectin-9 has recently been identified as a potential biomarker in patients with chronic liver disease. The objective of this study was to determine whether Galectin-9 and other serum proteins are associated with active disease in AIH patients.We enrolled 77 Japanese patients with well-documented AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 27 patients with SLE, and 17 healthy control subjects. Serum levels of galectin-9, and markers of liver injury were measured and compared between groups.Serum levels of galectin-9 were significantly higher in AIH patients than in CHC patients (13.8 ± 4.9 ng/mL vs 8.9 ± 3.0 ng/mL, P < .001) or healthy controls (13.8 ± 4.9 ng/mL vs 5.0 ± 1.3 ng/mL, P < .001). In AIH group, serum galectin-9 levels weakly correlated with alanine aminotransferase levels or total bilirubin (TB) and strongly correlated with C-X-C motif chemokine 10 (CXCL10) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum galectin-9 levels (14.1 ± 4.9 ng/mL vs 8.3 ± 3.8 ng/mL, P < .001). SLE patients exhibited higher galectin-9 levels, whereas the galectin-9 levels did not correlate with liver function tests such as alanine aminotransferase levels.Serum galectin-9 correlated with disease status in AIH patients and could thus be useful biomarkers to detect hepatic autoimmunity. Because circulating galectin-9 reflects autoimmune-mediated inflammation, it may have additional utility as a biomarker for other autoimmune disorders.

Project description:Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis progression to cirrhosis to HCC. We identified a panel of four serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.

Dataset Information

Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis.

Publications

Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis.

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