# Elevated Serum Soluble Tim-3 in Primary Biliary Cholangitis: Lack of Correlation with Cytokines, Chemokines, and Clinical Parameters

## TL;DR

The study found that elevated soluble Tim-3 in primary biliary cholangitis does not correlate with disease severity or cytokine levels, but other markers like MLR and IL-6 are strong predictors of prognosis.

## Contribution

The study identifies novel independent predictors of disease severity and prognosis in primary biliary cholangitis, despite no significant role for sTim-3 or Galectin-9.

## Key findings

- PBC patients had elevated sTim-3 and reduced Galectin-9 compared to controls, but neither correlated with clinical parameters.
- MLR, A/G ratio, TNF-α, IL-6, and CX3CL1 were independent predictors of disease severity and prognosis in PBC.
- Inflammatory markers like IL-6 and CX3CL1 strongly correlated with liver disease progression indicators like MELD and FIB-4.

## Abstract

Soluble Tim-3 (sTim-3) has been implicated in primary biliary cholangitis (PBC), an autoimmune liver disease, though its clinical significance remains unclear. This study aimed to evaluate the associations between sTim-3, Galectin-9, and cytokines in PBC, as well as their potential prognostic utility.

A total of 55 PBC patients were enrolled (45 without overlapping conditions) and serum levels of sTim-3, Galectin-9, and 18 cytokines/chemokines were measured. Disease severity was assessed using the model for end-stage liver disease (MELD), MELD-Na, and Mayo risk score (MRS) 1994, alongside fibrosis-4 (FIB-4) index and monocyte-lymphocyte ratio (MLR). Patients were stratified by fibrosis stage, cirrhosis status, Child-Pugh score, and treatment duration, with intergroup parameter comparisons performed. The least absolute shrinkage and selection operator regression identified potential risk factors for MRS1994, followed by multivariate linear regression analysis.

Compared to healthy controls, PBC patients exhibited elevated sTim-3 and reduced Galectin-9, though neither biomarker correlated with clinical parameters. Advanced disease stages were associated with increased MLR, interferon-gamma (IFN-γ), interleukin (IL)-6, IL-8, C-C motif chemokine ligand 3 (CCL3), CCL20, and C-X3-C motif chemokine ligand 1 (CX3CL1). The MELD/MELD-Na scores strongly correlated with IL-6, TNF-α, IFN-γ, CCL3, and CCL20, while IL-6 and CX3CL1 linked to FIB-4 index. Multivariate analysis identified MLR, albumin/globulin (A/G) ratio, TNF-α, IL-6, and CX3CL1 as independent predictors of MRS1994.

Although sTim-3 and Galectin-9 dysregulation lacked direct clinical relevance, MLR, A/G ratio, cirrhosis status, and inflammatory markers (TNF-α, IL-6, CX3CL1) emerged as robust predictors of disease severity (MELD) and prognosis (MRS1994), highlighting their potential for non-invasive risk stratification in PBC.