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

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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Main Authors: Michela Miglianti, Stefano Mocci, 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, Andrea Perra, Luchino Chessa
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
Subjects:
HLA-G
primary biliary cholangitis
ursodeoxicholic acid
Sardinia (Italy)
autoimmune diseases
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1585535/full
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Summary: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.
ISSN:1664-3224

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