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The role of HLA-G in primary biliary cholangitis and response to therapy

Title: The role of HLA-G in primary biliary cholangitis and response to therapy
Authors: Miglianti M.; Mocci S.; Littera R.; Serra G.; Balestieri C.; Conti M.; Pes F.; Deidda S.; Lorrai M.; Mereu C.; Murgia M.; Sanna C.; Mascia A.; Sedda F.; Dus-Ilnicka I.; Cipri S.; Carta M. G.; Lai S.; Giuressi E.; Melis M.; Zolfino T.; Giglio S.; Perra A.; Chessa L.
Contributors: Miglianti, M.; Mocci, S.; Littera, R.; Serra, G.; Balestieri, C.; Conti, M.; Pes, F.; Deidda, S.; Lorrai, M.; Mereu, C.; Murgia, M.; Sanna, C.; Mascia, A.; Sedda, F.; Dus-Ilnicka, I.; Cipri, S.; Carta, M. G.; Lai, S.; Giuressi, E.; Melis, M.; Zolfino, T.; Giglio, S.; Perra, A.; Chessa, L.
Publisher Information: Frontiers Research Foundation
Publication Year: 2025
Subject Terms: Autoimmune diseases; HLA-G; Primary biliary cholangitis; Sardinia (Italy); Ursodeoxicholic acid
Description: Introduction: Primary 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. Methods: A 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. Results: The 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). Discussion: These findings suggest HLA-G variants, especially HLA-G*01:01:01:08/UTR-1, as potential biomarkers for PBC prognosis and treatment outcomes.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40799641; info:eu-repo/semantics/altIdentifier/wos/WOS:001547334300001; volume:16; journal:FRONTIERS IN IMMUNOLOGY; https://hdl.handle.net/20.500.11768/196341; https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1585535/full
DOI: 10.3389/fimmu.2025.1585535
DOI: 10.3389/fimmu.2025.1585535/full
Availability: https://hdl.handle.net/20.500.11768/196341; https://doi.org/10.3389/fimmu.2025.1585535; https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1585535/full
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.2FC6A57
Database: BASE