# Diagnostic potential of salivary biomarkers for primary biliary cholangitis: a systematic review

**Authors:** Mahnoor Saeed, Muhammad Saad Shaikh, Alhanouf Binhezaim, Tahani Almutairi, Mohid Abrar Lone, Syed Jawad Ali Bukhari, Muhammad Sohail Zafar

PMC · DOI: 10.3389/fmed.2025.1670206 · 2026-01-15

## TL;DR

This review explores whether saliva can help diagnose primary biliary cholangitis by analyzing specific biomarkers and proteins.

## Contribution

The study systematically evaluates the potential of salivary biomarkers for diagnosing primary biliary cholangitis.

## Key findings

- Salivary AMA-M2 and PDC-E2 antibodies showed high diagnostic specificity for PBC.
- Inflammatory cytokines like IL-6 and TNF-α were elevated in PBC patients.
- Proteomic changes, including cystatin S-type and S100A proteins, distinguished PBC from healthy controls.

## Abstract

Recent studies have explored saliva as a non-invasive diagnostic fluid across various systemic and autoimmune conditions. However, its potential role in diagnosing primary biliary cholangitis (PBC) remains unclear.

This systematic review examines whether salivary biomarkers can assist in the diagnosis of PBC.

Indexed databases (PubMed and Scopus) and bibliographies of relevant articles were searched between November 2024 and December 2024. Original cross-sectional studies investigating salivary biomarkers specifically for PBC diagnosis were included. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) critical appraisal checklist.

Three studies involving 204 participants met the inclusion criteria. Salivary antimitochondrial antibodies-M2 (AMA-M2), pyruvate dehydrogenase complex E2 (PDC-E2) related autoantibodies, and inflammatory cytokines [interleukin (IL)-6, IL-17A, interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α)] were consistently elevated in PBC patients compared with healthy controls. Proteomic alterations, particularly increased cystatin S-type proteins and altered S100A family proteoforms, also differentiated PBC from healthy groups. Among all markers, AMA-M2 and PDC-E2 specific antibodies demonstrated the highest diagnostic specificity.

Available evidence suggests that select salivary autoantibodies and inflammatory proteins may hold diagnostic potential for PBC. Although promising, current data are limited, and larger, standardised studies are required to validate these biomarkers for clinical use.

## Linked entities

- **Proteins:** DLAT (dihydrolipoamide S-acetyltransferase), IL17A (interleukin 17A)
- **Diseases:** primary biliary cholangitis (MONDO:0005388), PBC (MONDO:0005388)

## Full-text entities

- **Genes:** CST4 (cystatin S) [NCBI Gene 1472], DLAT (dihydrolipoamide S-acetyltransferase) [NCBI Gene 1737] {aka DLTA, E2, PBC, PDC-E2, PDCE2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}
- **Diseases:** autoimmune conditions (MESH:D001327), PBC (MESH:D008105), inflammatory (MESH:D007249), inflammatory cytokines (MESH:D000080424)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12852463/full.md

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Source: https://tomesphere.com/paper/PMC12852463