Soluble immune checkpoints are elevated in patients with primary biliary cholangitis

Area of Science:

• Immunology
• Hepatology
• Autoimmune Diseases

Background:

• Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease with unknown etiology and pathogenesis.
• Immune checkpoints are crucial in preventing autoimmunity, but their role in PBC remains uninvestigated.
• This study aimed to determine serum levels of soluble immune checkpoints in PBC patients.

Purpose of the Study:

• To identify and quantify serum levels of soluble immune checkpoints in patients with primary biliary cholangitis (PBC).
• To assess the association of these soluble checkpoints with disease progression and liver function.
• To evaluate the diagnostic performance of soluble checkpoints for PBC and its severity.

Main Methods:

• Enzyme-linked immunosorbent assay (ELISA) was used to measure soluble checkpoint levels in 60 PBC patients and 20 healthy controls (HCs).
• Immunohistochemistry analyzed immune checkpoint expression in liver biopsy tissues.
• Receiver operating characteristic (ROC) curve analysis determined diagnostic accuracy for PBC and disease staging.

Main Results:

• Significantly increased serum levels of sCD134, sLAG-3, sPD-1, sPD-L1, and sTIM-3 were observed in PBC patients compared to HCs.
• Elevated levels of sCD134, sPD-1, sPD-L1, and sTIM-3 correlated positively with PBC disease progression.
• High diagnostic accuracy (AUCs up to 0.971) was achieved for sOX40, sPD-1, and sPD-L1 in distinguishing PBC patients from HCs.

Conclusions:

• Serum levels of soluble immune checkpoints are significantly elevated in Chinese patients with primary biliary cholangitis.
• Specific soluble checkpoints demonstrate potential as diagnostic biomarkers for PBC and indicators of disease severity.