# Diagnostic significance of salivary and glandular siglec-5 in Sjögren disease and non-Sjögren sicca

## TL;DR

This study explores the role of siglec-5 in diagnosing Sjögren disease and differentiating it from non-Sjögren sicca using salivary and glandular markers.

## Contribution

The study identifies siglec-5 as a potential objective biomarker for Sjögren disease with diagnostic value in salivary and glandular tissues.

## Key findings

- Salivary siglec-5 levels were significantly higher in Sjögren disease compared to non-Sjögren sicca.
- Siglec-5 tissue infiltration showed better diagnostic accuracy than salivary or ocular tests for Sjögren disease.
- Siglec-5 expression was associated with immune markers like CD20 and CD3 in glandular tissue.

## Abstract

Sjögren disease (SjD) has a multifactorial pathogenesis that is not fully understood. Perceptions of disease severity shape healthcare-seeking behavior and engagement with diagnostic assessments, underscoring the need for objective biomarkers. Sialic acid-binding immunoglobulin-like lectins (siglecs) have emerged as relevant mediators in SjD immunopathology.

To investigate the diagnostic performance of siglec-5 expression in minor salivary gland (MSG) tissue and saliva samples from individuals with SjD and non-Sjögren sicca (nSS).

A total of 109 participants with SjD and 41 with nSS were included. Salivary concentrations of siglec-5/siglec-14, inflammatory markers (IL-6, IL-8, IFN-γ, IgA, IgG, nitric oxide [NO]), and neutrophil extracellular traps (NETs) were measured. Immunohistochemical analyses of siglec-5, CD20, and CD3 were performed on MSG specimens. The data were analyzed descriptively and analytically.

Salivary levels of siglec-5/siglec-14, IgA, IgG, NO, and NETs were significantly higher in the SjD group compared to the nSS group. Elevated salivary levels of siglec-5/siglec-14, IL-6, and IgG were found among individuals with severe dryness scores. Immunohistochemical staining for siglec-5 was more pronounced in SjD samples and significantly associated with CD20 and CD3 positivity as well as the presence of xerophthalmia. Tissue infiltration by siglec-5 had greater diagnostic accuracy for SjD (area under the curve: 73.1% [95% confidence interval: 58.2–85]) than both salivary and ocular sicca tests.

Siglec-5 expression was increased in individuals with SjD, supporting its involvement in disease pathogenesis as well as its potential usefulness as a biomarker. The availability of objective salivary and tissue markers may improve diagnostic pathways for SjD, thereby facilitating patient engagement.

The online version contains supplementary material available at 10.1007/s00011-026-02188-8.