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

BACKGROUND: 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. PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.