IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.

<h4>Background</h4>Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC) in the next decade. Recent findings have demonstrated that Squamous cell carcinoma antigen 1 (SCCA1) and 2 (SCCA2) isoforms, now classified as serpi...

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Autores principales: Alessandra Biasiolo, Natascia Tono, Mariagrazia Ruvoletto, Santina Quarta, Cristian Turato, Gianmarco Villano, Luca Beneduce, Giorgio Fassina, Carlo Merkel, Angelo Gatta, Patrizia Pontisso
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:9a0a5b9b21d94c7fa158502de8981db82021-11-18T07:12:32ZIgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.1932-620310.1371/journal.pone.0040658https://doaj.org/article/9a0a5b9b21d94c7fa158502de8981db82012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22808225/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC) in the next decade. Recent findings have demonstrated that Squamous cell carcinoma antigen 1 (SCCA1) and 2 (SCCA2) isoforms, now classified as serpinB3 and serpinB4, are over-expressed in HCC, but not in normal liver. As reported, high levels of circulating SCCA-IgM immunocomplexes in patients with cirrhosis are significantly associated with HCC development.<h4>Aim</h4>To ascertain whether IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels.<h4>Methodology and findings</h4>79 patients with chronic liver disease were studied, including 17 patients with chronic hepatitis, 36 patients with cirrhosis and 26 with HCC. 28 blood donors were used as control. Monoclonal antibodies against serpinB3 and serpinB4 were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immunocomplexes were detected by commercially available ELISA assay. Overall, the results revealed a better diagnostic sensitivity of total SCCA-IgM assay, compared to both serpinB3 and serpinB4 IgM-linked assays. SerpinB4-IgM median values obtained with SCC103 antibody were moderately higher in patients with cirrhosis than in those with HCC, median values: 0.168 (IQR 0.140-0.427) vs. 0.140 (IQR 0.140-0.278), (p = 0.177). A trend toward decreasing serpinB4-IgM/serpinB3-IgM median ratio was observed in patients with advanced liver disease, being 1.08 in patients with HCC, 1.10 in patients with cirrhosis and 1.40 in patients with chronic hepatitis (p = 0.079).<h4>Conclusions</h4>IgM-linked SCCA isoforms in serum of patients with chronic liver diseases were quantified for the first time. Although the number of patients was limited, this preliminary study reveals that the relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM ratio, determined by lower serpinB4 levels.Alessandra BiasioloNatascia TonoMariagrazia RuvolettoSantina QuartaCristian TuratoGianmarco VillanoLuca BeneduceGiorgio FassinaCarlo MerkelAngelo GattaPatrizia PontissoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e40658 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Alessandra Biasiolo
Natascia Tono
Mariagrazia Ruvoletto
Santina Quarta
Cristian Turato
Gianmarco Villano
Luca Beneduce
Giorgio Fassina
Carlo Merkel
Angelo Gatta
Patrizia Pontisso
IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.
description <h4>Background</h4>Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC) in the next decade. Recent findings have demonstrated that Squamous cell carcinoma antigen 1 (SCCA1) and 2 (SCCA2) isoforms, now classified as serpinB3 and serpinB4, are over-expressed in HCC, but not in normal liver. As reported, high levels of circulating SCCA-IgM immunocomplexes in patients with cirrhosis are significantly associated with HCC development.<h4>Aim</h4>To ascertain whether IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels.<h4>Methodology and findings</h4>79 patients with chronic liver disease were studied, including 17 patients with chronic hepatitis, 36 patients with cirrhosis and 26 with HCC. 28 blood donors were used as control. Monoclonal antibodies against serpinB3 and serpinB4 were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immunocomplexes were detected by commercially available ELISA assay. Overall, the results revealed a better diagnostic sensitivity of total SCCA-IgM assay, compared to both serpinB3 and serpinB4 IgM-linked assays. SerpinB4-IgM median values obtained with SCC103 antibody were moderately higher in patients with cirrhosis than in those with HCC, median values: 0.168 (IQR 0.140-0.427) vs. 0.140 (IQR 0.140-0.278), (p = 0.177). A trend toward decreasing serpinB4-IgM/serpinB3-IgM median ratio was observed in patients with advanced liver disease, being 1.08 in patients with HCC, 1.10 in patients with cirrhosis and 1.40 in patients with chronic hepatitis (p = 0.079).<h4>Conclusions</h4>IgM-linked SCCA isoforms in serum of patients with chronic liver diseases were quantified for the first time. Although the number of patients was limited, this preliminary study reveals that the relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM ratio, determined by lower serpinB4 levels.
format article
author Alessandra Biasiolo
Natascia Tono
Mariagrazia Ruvoletto
Santina Quarta
Cristian Turato
Gianmarco Villano
Luca Beneduce
Giorgio Fassina
Carlo Merkel
Angelo Gatta
Patrizia Pontisso
author_facet Alessandra Biasiolo
Natascia Tono
Mariagrazia Ruvoletto
Santina Quarta
Cristian Turato
Gianmarco Villano
Luca Beneduce
Giorgio Fassina
Carlo Merkel
Angelo Gatta
Patrizia Pontisso
author_sort Alessandra Biasiolo
title IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.
title_short IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.
title_full IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.
title_fullStr IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.
title_full_unstemmed IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.
title_sort igm-linked serpinb3 and serpinb4 in sera of patients with chronic liver disease.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/9a0a5b9b21d94c7fa158502de8981db8
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