Serum Protein 90K/Mac-2BP Is an Independent Predictor of Disease Severity during Hepatitis C Virus Infection

Kittl, Eva Maria; Hofmann, Jörg; Hartmann, Gerold; Sebesta, Christian; Beer, Franz; Bauer, Katrin; Huber, Klaus

doi:10.1515/cclm.2000.029

Cited by 29 publications

(18 citation statements)

References 13 publications

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“…This is consistent with the findings of cross-sectional studies which showed a positive association between the 90K level and the severity of HCV infection [11,12].…”

supporting

confidence: 92%

Temporal Trend in the Level of 90K Glycoprotein after HIV Seroconversion among Persons Coinfected with Hepatitis C Virus

et al. 2005

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The secretory glycoprotein 90K is present in human fluids, including plasma, breast milk, saliva, tears, and urine [1,2], and in a wide range of epithelial tissues [1][2][3][4][5]. High levels of the serum glycoprotein 90K have been found in individuals infected with human immunodeficiency virus (HIV), hepatitis viruses B (HBV), or C (HCV) [6][7][8]. Up to now, the 90K level has been shown to predict HIV disease progression; however, whether HCV coinfection may alter this parameter among HIV-infected individuals is still undefined.We report the case of an HIV-HCV-coinfected male patient of 25 years of age at HIV seroconversion, who presented with a high 90K level which was predictive of development of liver cirrhosis. The 90K level was measured using an enzyme-linked immunosorbent assay (ELISA). The patient was enrolled in the Italian HIV-Seroconversion Study (ISS) [9]. One year after HIV seroconversion, the patient was positive for HCV. The 90K value was 5.0 µg/ml at 2 years after HIV seroconversion, and three other measurements were performed during the following 3 years. An increasing linear trend was observed in the 90K level during the 5 years: from 5.0 µg/ml to 18.2 µg/ml. During the same period, the CD4 cell count decreased from 519/mmc to 364/mmc and he remained asymptomatic, with an HIV load ranging from 3,352 copies to 3,400 copies. Six years after HIV seroconversion, the patient began combined antiretroviral treatments with zidovudine, lamivudine, and stavudine. Five years after the last 90K measurement (which was 18.2 µg/ml), the patient developed liver cirrhosis.This report suggests that 90K levels, among HIV/HCVcoinfected patients developing advanced liver disease, may be high, independent of HIV disease progression. This is consistent with the findings of cross-sectional studies which showed a positive association between the 90K level and the severity of HCV infection [11,12].In order to better investigate the relationship between 90K and HIV/HCV coinfection over time among a larger number of persons followed since HIV serconversion, we analyzed the data derived from the entire cohort considering those persons for whom at least one frozen serum sample was available and who had undergone HCV testing.Overall, 91 persons meeting these criteria were included in the analysis. For the evaluation of mean changes in the 90K level over time, 310 measurements were available. The measurements of the 90K level after the introduction of highly active antiretroviral therapy (HAART) were excluded from the analysis. The mean changes per year in the 90K level were estimated using mixed effects regression models [10]. The variables considered in the univariate models were: log 10 transformed 90K level, coinfection with HCV, age at HIV seroconversion, gender, duration of HIV infection, and AIDS status. Covariates with a pvalue of less than 0.05 and age at HIV seroconversion were entered in the multiple model. The slopes of the 90K measurements over time from HIV seroconversion were also estimated. Individuals were f...

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“…This is consistent with the findings of cross-sectional studies which showed a positive association between the 90K level and the severity of HCV infection [11,12].…”

supporting

confidence: 92%

Temporal Trend in the Level of 90K Glycoprotein after HIV Seroconversion among Persons Coinfected with Hepatitis C Virus

et al. 2005

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“…In addition, cells with higher expression of Mac-2BP displayed stronger adhesion to vitronectin but reduced adhesion to laminin and collagen IV, the 2 major components of basal lamina, implying that through favoring cell-cell aggregation and inhibiting cell adhesion to basal lamina, Mac-2BP maybe keep EWS cells in fluid blood circulation, where they are more prone to die, and prevent EWS cell adhesion to endothelium and extravasation (51). In liver diseases, serum 90K/Mac-2BP was found as an independent predictor of disease severity during HCV infection (52). In another report, serum Mac-2BP was evaluated in 11 chronic active hepatitis, 48 liver cirrhosis and 36 hepatocellular carcinoma.…”

Section: Resultsmentioning

confidence: 99%

Development of Glycoprotein Capture-Based Label-Free Method for the High-throughput Screening of Differential Glycoproteins in Hepatocellular Carcinoma

Chen

Tan

Wang

et al. 2011

Molecular & Cellular Proteomics

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A robust, reproducible, and high throughput method was developed for the relative quantitative analysis of glycoprotein abundances in human serum. Instead of quantifying glycoproteins by glycopeptides in conventional quantitative glycoproteomics, glycoproteins were quantified by nonglycosylated peptides derived from the glycoprotein digest, which consists of the capture of glycoproteins in serum samples and the release of nonglycopeptides by trypsin digestion of captured glycoproteins followed by two-dimensional liquid chromatography-tandem MS analysis of released peptides. Protein quantification was achieved by comparing the spectrum counts of identified nonglycosylated peptides of glycoproteins between different samples. This method was demonstrated to have almost the same specificity and sensitivity in glycoproteins quantification as capture at glycopeptides level. The differential abundance of proteins present at as low as nanogram per milliliter levels was quantified with high confidence. The established method was applied to the analysis of human serum samples from healthy people and patients with hepatocellular carcinoma (HCC) to screen differential glycoproteins in HCC. Thirty eight glycoproteins were found with substantial concentration changes between normal and HCC serum samples, including ␣-fetoprotein, the only clinically used marker for HCC diagnosis. The abundance changes of three glycoproteins, i.e. galectin-3 binding protein, insulin-like growth factor binding protein 3, and thrombospondin 1, which were associated with the development of HCC, were further confirmed by enzyme-linked immunosorbent assay. In conclusion, the developed method was an effective approach to quantitatively analyze glycoproteins in human serum and could be further applied in the biomarker discovery for HCC and other cancers. Molecular

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“…Evidence of these alterations in hepatitis C has been provided by Bigger et al., reporting a change in hepatic gene regulation during course and clearance of viral hepatitis C in primates [48]. Also, previous studies have associated increased serum galectin-3-binding protein levels with viral genotype 1 -4 [13, 14,16,19]. According to these findings, galectin-3-binding protein is likely a hepatitis C-specific marker of fibrosis rather than a universal fibrosis marker, despite significant increase in proteinlevel in both pathologies.…”

Section: Discussionmentioning

confidence: 97%

“…Galectin-3-binding protein is a secreted 90 kDa Nglycosylated protein with affinity for galectins as well as extracellular matrix proteins [12]. Sudden increase in serum galectin-3-binding protein levels have been reported in various infectious and cancerous diseases, including hepatitis C [13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Galectin-3-binding protein: a serological and histological assessment in accordance with hepatitis C-related liver fibrosis

Cheung

Libbrecht²,

Tilleman³

et al. 2010

European Journal of Gastroenterology & Hepatology

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Objectives. Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of non-invasive alternatives, galectin-3-binding protein was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics.We investigated the role of galectin-3-binding protein as a single-marker of significant fibrosis and cirrhosis by means of serology and histology and studied the role of glycosylation on the expression in hepatitis C-and alcohol-related cirrhosis. Methods. Sera and available biopsies of hepatitis C patients with various fibrosis-gradesand patients with alcohol-related cirrhosis were used for galectin-3-binding protein measurements by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Glycosylation-effect was analyzed by Western blot. Data was analyzed in accordance to fibrosis.Results. Galectin-3-binding protein was increased during cirrhosis (22.7 ± 10.1 µg/mL) in contrast to mild (11.3 ± 6.4 µg/mL) and moderate fibrosis (13.4 ± 8.3 µg/mL) (p < 0.001; p = 0.004, respectively). Receiver operator characteristics curves showed areas under the curve of 0.68 and 0.81 for the detection of respectively significant fibrosis and cirrhosis. Similar findings in hepatic expression were obtained, in which cirrhosis was associated with diffuse, parenchymal expression (p = 0.002). The observed difference between hepatitis C-and alcohol-related cirrhosis (13.5 ± 9.0 µg/mL) (p = 0.009) could not be explained by glycosylation. (mean ± standard deviation) Conclusions. Our recent findings confirm our initial proteome results on serological and histological level as well as the role of galectin-3-binding protein as a marker of 4 4 hepatitis C-related fibrosis, especially cirrhosis. Implication of this protein in future multi-marker study should be considered.

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Serum Protein 90K/Mac-2BP Is an Independent Predictor of Disease Severity during Hepatitis C Virus Infection

Cited by 29 publications

References 13 publications

Temporal Trend in the Level of 90K Glycoprotein after HIV Seroconversion among Persons Coinfected with Hepatitis C Virus

Temporal Trend in the Level of 90K Glycoprotein after HIV Seroconversion among Persons Coinfected with Hepatitis C Virus

Development of Glycoprotein Capture-Based Label-Free Method for the High-throughput Screening of Differential Glycoproteins in Hepatocellular Carcinoma

Galectin-3-binding protein: a serological and histological assessment in accordance with hepatitis C-related liver fibrosis

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