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High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis
Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease frequently characterized by anti-mitochondrial autoantibodies (AMA). A minority of patients are AMA-negative. Cytotoxic-T-Lymphocyte-Antigen-4 (CTLA-4) is a surface molecule expressed on activated T-cells delivering a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226553/ https://www.ncbi.nlm.nih.gov/pubmed/25383768 http://dx.doi.org/10.1371/journal.pone.0112509 |
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author | Saverino, Daniele Pesce, Giampaola Antola, Princey Porcelli, Brunetta Brusca, Ignazio Villalta, Danilo Tampoia, Marilina Tozzoli, Renato Tonutti, Elio Alessio, Maria Grazia Bagnasco, Marcello Bizzaro, Nicola |
author_facet | Saverino, Daniele Pesce, Giampaola Antola, Princey Porcelli, Brunetta Brusca, Ignazio Villalta, Danilo Tampoia, Marilina Tozzoli, Renato Tonutti, Elio Alessio, Maria Grazia Bagnasco, Marcello Bizzaro, Nicola |
author_sort | Saverino, Daniele |
collection | PubMed |
description | Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease frequently characterized by anti-mitochondrial autoantibodies (AMA). A minority of patients are AMA-negative. Cytotoxic-T-Lymphocyte-Antigen-4 (CTLA-4) is a surface molecule expressed on activated T-cells delivering a critical negative immunoregulatory signal. A soluble form of CTLA-4 (sCTLA-4) has been detected at high concentrations in several autoimmune diseases, and its possible functional meaning has been suggested. We aimed to evaluate sCTLA-4 concentration in sera of patients with PBC and to correlate it to immunological abnormalities associated with the disease. Blood samples were collected from 82 PBC-patients diagnosed according to international criteria (44 AMA-positive/MIT3-positive and 38 AMA-negative-MIT3-negative), and 65 controls. sCTLA-4 levels were evaluated by ELISA and Western blot. Increased sCTLA-4 concentrations were found in all AMA-positive PBC-patients, but in none of the AMA-negative ones, nor in normal controls or in controls with unrelated liver diseases. sCTLA-4 presence was associated with autoantibodies against MIT3, but not with nuclear autoantibodies (sp100, gp210). This is the first study to demonstrate that levels of sCTLA-4 are elevated in sera of PBC patients. However, they are clearly restricted to patients with AMA positivity, suggesting an immunological difference with respect to AMA-negative ones. |
format | Online Article Text |
id | pubmed-4226553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42265532014-11-13 High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis Saverino, Daniele Pesce, Giampaola Antola, Princey Porcelli, Brunetta Brusca, Ignazio Villalta, Danilo Tampoia, Marilina Tozzoli, Renato Tonutti, Elio Alessio, Maria Grazia Bagnasco, Marcello Bizzaro, Nicola PLoS One Research Article Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease frequently characterized by anti-mitochondrial autoantibodies (AMA). A minority of patients are AMA-negative. Cytotoxic-T-Lymphocyte-Antigen-4 (CTLA-4) is a surface molecule expressed on activated T-cells delivering a critical negative immunoregulatory signal. A soluble form of CTLA-4 (sCTLA-4) has been detected at high concentrations in several autoimmune diseases, and its possible functional meaning has been suggested. We aimed to evaluate sCTLA-4 concentration in sera of patients with PBC and to correlate it to immunological abnormalities associated with the disease. Blood samples were collected from 82 PBC-patients diagnosed according to international criteria (44 AMA-positive/MIT3-positive and 38 AMA-negative-MIT3-negative), and 65 controls. sCTLA-4 levels were evaluated by ELISA and Western blot. Increased sCTLA-4 concentrations were found in all AMA-positive PBC-patients, but in none of the AMA-negative ones, nor in normal controls or in controls with unrelated liver diseases. sCTLA-4 presence was associated with autoantibodies against MIT3, but not with nuclear autoantibodies (sp100, gp210). This is the first study to demonstrate that levels of sCTLA-4 are elevated in sera of PBC patients. However, they are clearly restricted to patients with AMA positivity, suggesting an immunological difference with respect to AMA-negative ones. Public Library of Science 2014-11-10 /pmc/articles/PMC4226553/ /pubmed/25383768 http://dx.doi.org/10.1371/journal.pone.0112509 Text en © 2014 Saverino et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Saverino, Daniele Pesce, Giampaola Antola, Princey Porcelli, Brunetta Brusca, Ignazio Villalta, Danilo Tampoia, Marilina Tozzoli, Renato Tonutti, Elio Alessio, Maria Grazia Bagnasco, Marcello Bizzaro, Nicola High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis |
title | High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis |
title_full | High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis |
title_fullStr | High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis |
title_full_unstemmed | High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis |
title_short | High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis |
title_sort | high levels of soluble ctla-4 are present in anti-mitochondrial antibody positive, but not in antibody negative patients with primary biliary cirrhosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226553/ https://www.ncbi.nlm.nih.gov/pubmed/25383768 http://dx.doi.org/10.1371/journal.pone.0112509 |
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