Exploring salivary and lacrimal biomarkers in non-Sjögren sicca: A scoping review

Sicca symptoms may arise from a wide range of underlying etiologies. Non-Sjögren sicca (nSS) typically refers to individuals who experience sicca symptoms, but do not fulfill the immunological or histopathological criteria required for the diagnosis of Sjögren disease (SjD). Herein, we mapped the salivary and lacrimal molecular signatures reported in nSS and evaluated their potential utility in distinguishing nSS from SjD.

This scoping review included observational studies comparing salivary and/or lacrimal biomarkers between individuals with nSS and those with SjD. Data were synthesized descriptively.

A total of 38 studies examining salivary and/or lacrimal biomarkers were included. The diagnostic criteria used to define SjD and nSS varied considerably across studies. Inflammatory molecules, including beta-2 microglobulin, interleukins, chemokines, growth factors, and enzymes, were consistently found at lower levels in both the saliva and tears of individuals with nSS. In contrast, salivary IFN-γ and lacrimal lactoferrin levels were higher in nSS, whereas some inflammatory molecules (TNF, IL-6, IL-1, IL-8, and IL-10) showed similar expression levels in both conditions. Salivary autoantibodies were identified in 30-60% of individuals with nSS.

nSS is a biologically heterogeneous condition characterized by broad alterations in salivary and lacrimal composition. Although immune-inflammatory activation appears to be lower in nSS, autoantibody positivity and levels of certain inflammatory markers comparable to those observed in SjD suggest that low-grade inflammation may contribute to the pathophysiology of nSS.