Serum Wisteria Floribunda Agglutinin-positive Mac-2 Research Articles

The role of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in the assessment of fibrosis in children with chronic hepatitis C

At present, noninvasive fibrosis markers are not available for the assessment of liver fibrosis in children with chronic hepatitis C. Sixty-three children with chronic hepatitis C were included. Changes in Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) levels were evaluated in l3 of 27 treatment-naive patients during the natural course of disease (median 4, range 3–6 years). Changes during treatment were evaluated in 27 of 36 patients for 4 (2–9) years of posttreatment follow-up. There were significant differences in the levels of M2BPGi between control group and HCV F0 group (P = 0.002) and between control group and HCV F1 group (P < 0.001). Receiver operating characteristic curve analysis showed that to discriminate stage F1 fibrosis from F0, the cut-off value was 0.95 for M2BPGi with a sensitivity of 52%, specificity of 90%, and area under the curve of 0.687. A substantial decrease in M2BPGi levels by treatment was shown from 0.98 ± 0.57 at pretreatment to 0.42 ± 0.15 at posttreatment (P < 0.001) in the 27 treated patients. Our study shows new findings that M2BPGi may be useful to predict the presence of a mild degree of fibrosis in children with chronic hepatitis C, and such mild fibrosis may be quickly resolved by treatment.

Use of the Serum Wisteria floribunda Agglutinin-Positive Mac2 Binding Protein as a Marker of Gastroesophageal Varices and Liver-Related Events in Chronic Hepatitis C Patients.

Background: A test to narrow down patients who require esophagogastroduodenoscopy (EGD) with a high probability of having gastroesophageal varices (GEV) and a high-risk of liver-related events is an unmet need. Methods: The measurement of serum fibrosis markers and EGD was performed in 166 consecutive chronic hepatitis C patients. The correlation between the grades of GEV and fibrosis markers and the subsequent occurrence of liver-related and fibrosis markers were examined. Results: Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+–M2BP) levels increased according to the grade of GEV (3.4 (0.2–18.6) for no GEV, 7.9 (1.8–20.0) for small GEV, and 11.4 (4.0–20.0) for large GEV; p < 0.001). The diagnostic accuracy of the WFA+–M2BP was superior compared to other serum fibrosis markers, and WFA+–M2BP was an independent predictor of GEV in the multivariate analysis. Furthermore, the cumulative incidence of liver-related events at one year was 2.3% in patients with WFA+–M2BP levels ≤ 7.0 and 37.5% in patients with WFA+–M2BP levels > 7.0 (p < 0.001). WFA+–M2BP > 7.0 was a significant predictive factor for liver-related events (Hazard ratio 6.7, p = 0.004) independent of Child–Pughclass. Conclusions: WFA+–M2BP could be used to estimate the presence and grade of GEV and is linked to liver-related events in chronic hepatitis C patients.

Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts early occurrence of hepatocellular carcinoma after sustained virologic response by direct-acting antivirals for hepatitis C virus.

The aim of this study is to clarify the value of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) for predicting hepatocellular carcinoma (HCC) in chronic hepatitis C patients who achieved sustained virologic response (SVR) by therapy with interferon-free, direct-acting antivirals (DAAs). This is a retrospective cohort study that included 567 patients who underwent antiviral therapy with an interferon-free DAA regimen and achieved SVR. Serum WFA+ -M2BP was measured after SVR. Factors predictive of HCC occurrence and recurrence were analyzed in the patients after stratification by previous treatment history of HCC. Among 518 patients who had no history of HCC, 13 developed HCC. Post-SVR WFA+ -M2BP ≥1.75 cut-off index (C.O.I., P < 0.001) and α-fetoprotein (AFP) level ≥6ng/mL (P = 0.01) were significant predictors of HCC development. Multivariate analysis showed that post-SVR WFA+ -M2BP ≥1.75 C.O.I. was an independent factor significantly associated with the development of HCC (hazard ratio [HR] 6.0; 95% confidence interval (CI), 1.8-19.4; P = 0.003). Among 49 patients who had a previous history of HCC, 22 had recurrence after SVR. Post-SVR AFP ≥6ng/mL was the only factor associated with recurrence-free survival (HR 3.1; 95% CI, 1.3-7.5; P = 0.01). Post-SVR WFA+ -M2BP is a predictive factor for the development of HCC in patients with no previous HCC history and treated with DAAs. Post-SVR AFP was predictive for HCC recurrence after DAA therapy.

Serum levels of Wisteria floribunda agglutinin‐positive Mac‐2 binding protein reflect the severity of chronic pancreatitis

To evaluate the utility of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA + -M2BP) level as a marker for chronic pancreatitis (CP). We measured the serum WFA+ -M2BP level of 74 patients with CP who had undergone endoscopic retrograde cholangiopancreatography and 30 normal controls (NC) using a glycan sugar chain-based immunoassay and investigated the relationship between serum WFA+ -M2BP levels and the Cambridge classification of CP. Serum WFA+ -M2BP level was significantly higher in patients with CP than in NC (0.64 ± 0.28 vs 0.34 ± 0.25, P < 0.001). The levels (expressed as cut-off index) of WFA+ -M2BP for the classification of mild, moderate and marked CP were 0.44, 0.63 and 0.87, respectively. Thus, serum WFA+ -M2BP levels increased with increasing CP severity. With a cut-off value of 0.34, 0.59 and 0.61, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.829, 91.9% and 63.3% for mild CP; 0.891, 81.8% and 85.0% for moderate CP; and 0.888, 92.0% and 74.7% for marked CP, respectively. Multivariate analysis revealed that elevated serum WFA+ -M2BP was independently associated with moderate and marked CP, respectively. Serum WFA+ -M2BP level is a useful marker for grading CP severity.

Sa1323 - Clinical Significance of Serum Wisteria Floribunda Agglutinin-Positive MAC-2 Binding Protein in Pancreatic Ductal Adenocarcinoma

Sa1323 - Clinical Significance of Serum Wisteria Floribunda Agglutinin-Positive MAC-2 Binding Protein in Pancreatic Ductal Adenocarcinoma

Clinical significance of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in pancreatic ductal adenocarcinoma

BackgroundWisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA+-M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis. MethodsIn this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA+-M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA+-M2BP, we investigated the presence of WFA+-M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53). The bio-physiological effects of MDA-PATC53 supernatant were evaluated. Finally, the difference in the expression of glycosylation enzymes between MDA-PATC53 and Panc-1 were analyzed by cDNA microarray. ResultsWe found that the serum WFA+-M2BP level could distinguish the 2 groups. The median serum COI of WFA+-M2BP was 0.98 and 0.51 in PDAC and CP, respectively. Additionally, WFA+-M2BP positive PDACs were more frequently associated with metastatic lesions than the WFA+-M2BP negative PDACs (91.6% vs. 41.7%, P = 0.009). The MDA-PATC53 cells alone produced WFA+-M2BP. However, we found that MDA-PATC53 supernatant containing WFA+-M2BP (1.0 COI) did not alter the biological behavior of cancer cell lines. The results of cDNA microarray revealed that several glycosylation enzymes with pro-oncologic function were highly expressed in MDA-PATC53 compared to Panc-1. ConclusionsSerum WFA+-M2BP can be a useful biomarker for the diagnosis of PDAC and the prediction of disease progression since it potentially reflects altered pro-oncologic glycosylation enzymes.

Increased levels of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in idiopathic pulmonary fibrosis

BackgroundMac-2 binding protein (M2BP) is a cell-adhesive glycoprotein of the extracellular matrix secreted as a ligand of galectin-3 (Mac-2). Recently, a Wisteria floribunda agglutinin positive-M2BP (WFA+-M2BP) assay developed using a lectin-antibody sandwich immunoassay has shown promise as a new fibrotic marker in liver fibrosis to detect unique fibrosis-related glycoalteration. The aim of this study is to evaluate the utility of serum WFA+-M2BP levels in patients with idiopathic pulmonary fibrosis (IPF). MethodsWe measured serum WFA+-M2BP levels in 116 patients with IPF and 42 healthy volunteers. We examined the relationship between serum WFA+-M2BP levels and clinical parameters and further investigated the prognostic significance of serum WFA+-M2BP levels in patients with IPF. ResultsSerum WFA+-M2BP levels were significantly higher in patients with IPF than in healthy controls (1.09 ± 0.89 cutoff index [COI], 0.57 ± 0.24 COI, respectively; P < 0.001). In patients with IPF, a significant positive correlation was found between serum WFA+-M2BP levels and age, KL-6, neutrophils in BAL, reticulation and honeycombing scores in HRCT, and fibrotic foci scores in pathological findings, and a significant negative correlation was found between serum WFA+-M2BP levels and FVC, %DLco and macrophages in BAL. Furthermore, patients with high serum WFA+-M2BP levels had a significantly worse prognosis than those with low levels (log-rank test, P = 0.0209), and a high serum WFA+-M2BP level was a significant prognostic factor in Cox proportional hazards regression analysis. ConclusionsOur results suggest that the serum WFA+-M2BP level is a potential biomarker in patients with IPF.

非アルコール性脂肪性肝疾患の肝線維化経過観察における血清Mac2結合蛋白糖鎖修飾異性体の測定意義：反復肝生検症例からの検討

非アルコール性脂肪性肝疾患の肝線維化経過観察における血清Mac2結合蛋白糖鎖修飾異性体の測定意義：反復肝生検症例からの検討

Association between Wisteria floribunda agglutinin-positive Mac-2 binding protein and the fibrosis stage of non-alcoholic fatty liver disease.

Accurately evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) is important for identifying those who may develop complications. The aims of this study were (1) to measure serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP) using the glycan sugar chain-based immunoassay and (2) to compare the results with clinical assessments of fibrosis. Serum WFA(+)-M2BP values were retrospectively evaluated in 289 patients with NAFLD who had undergone liver biopsy. Histological findings were evaluated by three blinded, experienced liver-specific pathologists. For stages 0 (n = 35), 1 (n = 113), 2 (n = 49), 3 (n = 41), and 4 (n = 51) of liver fibrosis, the serum WFA(+)-M2BP cutoff indexes were 0.57, 0.70, 1.02, 1.57, and 2.96, respectively. Multivariate regression analysis showed that serum WFA(+)-M2BP values were associated with the stage of fibrosis (≥stage 2). The areas under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum WFA(+)-M2BP were 0.876, 85.9, and 74.6%, respectively, for severe fibrosis (≥stage 3) and were 0.879, 74.6, and 87.0%, respectively, for cirrhosis. When compared with six non-invasive conventional markers, serum WFA(+)-M2BP had the greatest AUROC for diagnosing severe fibrosis and cirrhosis. Serum WFA(+)-M2BP values are useful for assessing the stage of liver fibrosis in patients with NAFLD.