The role of HLA-G in primary biliary cholangitis and response to therapy
IntroductionPrimary biliary cholangitis (PBC) is a rare autoimmune liver disease involving bile duct damage and fibrosis. This study explores the role of HLA-G, an immunomodulatory molecule crucial for immune tolerance, in PBC pathogenesis and treatment.MethodsA cohort of 166 PBC patients from Sardi...
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Frontiers Media S.A.
2025-07-01
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| author | Michela Miglianti Stefano Mocci Stefano Mocci Roberto Littera Roberto Littera Giancarlo Serra Cinzia Balestieri Maria Conti Francesco Pes Silvia Deidda Michela Lorrai Caterina Mereu Michela Murgia Celeste Sanna Alessia Mascia Francesca Sedda Irena Duś-Ilnicka Selene Cipri Mauro Giovanni Carta Sara Lai Erika Giuressi Maurizio Melis Teresa Zolfino Sabrina Giglio Sabrina Giglio Sabrina Giglio Andrea Perra Andrea Perra Luchino Chessa Luchino Chessa |
| author_facet | Michela Miglianti Stefano Mocci Stefano Mocci Roberto Littera Roberto Littera Giancarlo Serra Cinzia Balestieri Maria Conti Francesco Pes Silvia Deidda Michela Lorrai Caterina Mereu Michela Murgia Celeste Sanna Alessia Mascia Francesca Sedda Irena Duś-Ilnicka Selene Cipri Mauro Giovanni Carta Sara Lai Erika Giuressi Maurizio Melis Teresa Zolfino Sabrina Giglio Sabrina Giglio Sabrina Giglio Andrea Perra Andrea Perra Luchino Chessa Luchino Chessa |
| author_sort | Michela Miglianti |
| collection | DOAJ |
| description | IntroductionPrimary biliary cholangitis (PBC) is a rare autoimmune liver disease involving bile duct damage and fibrosis. This study explores the role of HLA-G, an immunomodulatory molecule crucial for immune tolerance, in PBC pathogenesis and treatment.MethodsA cohort of 166 PBC patients from Sardinia was compared to 180 healthy controls and 205 autoimmune hepatitis type 1 (AIH-1) patients. Plasma soluble HLA-G (sHLA-G) levels, HLA-G alleles, and 3’UTR haplotypes were analyzed alongside clinical data, including therapy response to ursodeoxycholic acid.ResultsThe UTR-1 haplotype was significantly more frequent in PBC patients than in controls (48.2% vs 34.3%, Pc= 0.0018). The extended haplotype HLA-G*01:01:01:08/UTR-1 was also strongly associated with PBC (23.2% vs 12.5% in controls, Pc = 0.008; 23.2% vs 6.6% in AIH-1, Pc= 2.6×10-9). PBC patients exhibited lower sHLA-G levels compared to controls and AIH-1 (9.1 U/mL vs 24.03 U/mL and 13.9 U/mL, respectively). Among UTR-1 carriers, sHLA-G levels were particularly reduced in PBC patients. The HLA-G*01:01:01:08/UTR-1 haplotype correlated with the lowest sHLA-G levels and poorer therapy response (60% vs 24.1%, P = 0.0001).DiscussionThese findings suggest HLA-G variants, especially HLA-G*01:01:01:08/UTR-1, as potential biomarkers for PBC prognosis and treatment outcomes. |
| format | Article |
| id | doaj-art-52f4cd7931fc4a5798b7c0a805a6dd85 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-52f4cd7931fc4a5798b7c0a805a6dd852025-08-20T03:34:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15855351585535The role of HLA-G in primary biliary cholangitis and response to therapyMichela Miglianti0Stefano Mocci1Stefano Mocci2Roberto Littera3Roberto Littera4Giancarlo Serra5Cinzia Balestieri6Maria Conti7Francesco Pes8Silvia Deidda9Michela Lorrai10Caterina Mereu11Michela Murgia12Celeste Sanna13Alessia Mascia14Francesca Sedda15Irena Duś-Ilnicka16Selene Cipri17Mauro Giovanni Carta18Sara Lai19Erika Giuressi20Maurizio Melis21Teresa Zolfino22Sabrina Giglio23Sabrina Giglio24Sabrina Giglio25Andrea Perra26Andrea Perra27Luchino Chessa28Luchino Chessa29Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyCentre for Research University Services (CeSAR, Centro Servizi di Ateneo per la Ricerca), University of Cagliari, Cagliari, ItalyAART-ODV (Association for the Advancement of Research Transplantation), Cagliari, ItalyMedical Genetics, R. Binaghi Hospital, ASL Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyGastroenterology Unit, ARNAS Brotzu, Cagliari, ItalyGastroenterology Unit, ARNAS Brotzu, Cagliari, ItalyGastroenterology Unit, ARNAS Brotzu, Cagliari, ItalyPneumology Unit, R. Binaghi Hospital, ASSL Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyOncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyOncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyDepartment of Oral Pathology, Wrocław Medical University, Wrocław, PolandAART-ODV (Association for the Advancement of Research Transplantation), Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyMedical Genetics, R. Binaghi Hospital, ASL Cagliari, Cagliari, ItalyMedical Genetics, R. Binaghi Hospital, ASL Cagliari, Cagliari, ItalyAART-ODV (Association for the Advancement of Research Transplantation), Cagliari, ItalyGastroenterology Unit, ARNAS Brotzu, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyCentre for Research University Services (CeSAR, Centro Servizi di Ateneo per la Ricerca), University of Cagliari, Cagliari, ItalyMedical Genetics, R. Binaghi Hospital, ASL Cagliari, Cagliari, ItalyAART-ODV (Association for the Advancement of Research Transplantation), Cagliari, ItalyOncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy0Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, ItalyIntroductionPrimary biliary cholangitis (PBC) is a rare autoimmune liver disease involving bile duct damage and fibrosis. This study explores the role of HLA-G, an immunomodulatory molecule crucial for immune tolerance, in PBC pathogenesis and treatment.MethodsA cohort of 166 PBC patients from Sardinia was compared to 180 healthy controls and 205 autoimmune hepatitis type 1 (AIH-1) patients. Plasma soluble HLA-G (sHLA-G) levels, HLA-G alleles, and 3’UTR haplotypes were analyzed alongside clinical data, including therapy response to ursodeoxycholic acid.ResultsThe UTR-1 haplotype was significantly more frequent in PBC patients than in controls (48.2% vs 34.3%, Pc= 0.0018). The extended haplotype HLA-G*01:01:01:08/UTR-1 was also strongly associated with PBC (23.2% vs 12.5% in controls, Pc = 0.008; 23.2% vs 6.6% in AIH-1, Pc= 2.6×10-9). PBC patients exhibited lower sHLA-G levels compared to controls and AIH-1 (9.1 U/mL vs 24.03 U/mL and 13.9 U/mL, respectively). Among UTR-1 carriers, sHLA-G levels were particularly reduced in PBC patients. The HLA-G*01:01:01:08/UTR-1 haplotype correlated with the lowest sHLA-G levels and poorer therapy response (60% vs 24.1%, P = 0.0001).DiscussionThese findings suggest HLA-G variants, especially HLA-G*01:01:01:08/UTR-1, as potential biomarkers for PBC prognosis and treatment outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1585535/fullHLA-Gprimary biliary cholangitisursodeoxicholic acidSardinia (Italy)autoimmune diseases |
| spellingShingle | Michela Miglianti Stefano Mocci Stefano Mocci Roberto Littera Roberto Littera Giancarlo Serra Cinzia Balestieri Maria Conti Francesco Pes Silvia Deidda Michela Lorrai Caterina Mereu Michela Murgia Celeste Sanna Alessia Mascia Francesca Sedda Irena Duś-Ilnicka Selene Cipri Mauro Giovanni Carta Sara Lai Erika Giuressi Maurizio Melis Teresa Zolfino Sabrina Giglio Sabrina Giglio Sabrina Giglio Andrea Perra Andrea Perra Luchino Chessa Luchino Chessa The role of HLA-G in primary biliary cholangitis and response to therapy Frontiers in Immunology HLA-G primary biliary cholangitis ursodeoxicholic acid Sardinia (Italy) autoimmune diseases |
| title | The role of HLA-G in primary biliary cholangitis and response to therapy |
| title_full | The role of HLA-G in primary biliary cholangitis and response to therapy |
| title_fullStr | The role of HLA-G in primary biliary cholangitis and response to therapy |
| title_full_unstemmed | The role of HLA-G in primary biliary cholangitis and response to therapy |
| title_short | The role of HLA-G in primary biliary cholangitis and response to therapy |
| title_sort | role of hla g in primary biliary cholangitis and response to therapy |
| topic | HLA-G primary biliary cholangitis ursodeoxicholic acid Sardinia (Italy) autoimmune diseases |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1585535/full |
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