HLA-G在原发性胆汁性胆管炎中的作用及对治疗的反应。
The role of HLA-G in primary biliary cholangitis and response to therapy.
作者信息
Miglianti Michela, Mocci Stefano, Littera Roberto, Serra Giancarlo, Balestieri Cinzia, Conti Maria, Pes Francesco, Deidda Silvia, Lorrai Michela, Mereu Caterina, Murgia Michela, Sanna Celeste, Mascia Alessia, Sedda Francesca, Duś-Ilnicka Irena, Cipri Selene, Carta Mauro Giovanni, Lai Sara, Giuressi Erika, Melis Maurizio, Zolfino Teresa, Giglio Sabrina, Perra Andrea, Chessa Luchino
机构信息
Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
出版信息
Front Immunol. 2025 Jul 29;16:1585535. doi: 10.3389/fimmu.2025.1585535. eCollection 2025.
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, alleles, and 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 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). 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 carriers, sHLA-G levels were particularly reduced in PBC patients. The 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 , as potential biomarkers for PBC prognosis and treatment outcomes.
引言
原发性胆汁性胆管炎（PBC）是一种罕见的自身免疫性肝病，涉及胆管损伤和纤维化。本研究探讨免疫调节分子HLA - G在PBC发病机制和治疗中的作用，HLA - G对免疫耐受至关重要。
方法
将一组来自撒丁岛的166例PBC患者与180例健康对照者和205例1型自身免疫性肝炎（AIH - 1）患者进行比较。分析血浆可溶性HLA - G（sHLA - G）水平、等位基因和单倍型，并结合临床数据，包括对熊去氧胆酸的治疗反应。
结果
UTR - 1单倍型在PBC患者中显著比对照者更常见（48.2%对34.3%，Pc = 0.0018）。扩展单倍型也与PBC密切相关（对照者中为23.2%对12.5%，Pc = 0.008；AIH - 1中为23.2%对6.6%，Pc = 2.6×10）。与对照者和AIH - 1相比，PBC患者的sHLA - G水平较低（分别为9.1 U/mL对24.03 U/mL和13.9 U/mL）。在携带者中，PBC患者的sHLA - G水平尤其降低。单倍型与最低的sHLA - G水平和较差的治疗反应相关（60%对24.1%，P = 0.0001）。
讨论
这些发现表明HLA - G变体，尤其是，作为PBC预后和治疗结果的潜在生物标志物。
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