Oxford University Press, Rheumatology, 6(56), p. 1031-1038, 2017
DOI: 10.1093/rheumatology/kew501
Full text: Unavailable
Objectives: Salivary cystatin S, a defence protein mainly produced by submandibular glands and involved in innate oral immunity, has appeared as a promising candidate biomarkers for pSS in proteomic studies. This study aims to verify whether cystatin S was decreased in saliva of pSS patients and diversely expressed in different disease subsets defined on the basis of salivary flow (USFR), minor salivary gland focus score (MSG/FS) and submandibular glands ultrasonography abnormalities (SGUS). We also evaluated miR-126 and miR-335-5p expression in MSG biopsies to verify whether an aberrant regulation of cystatin S at glandular level may influence its salivary expression. Methods: Forty pSS patients and 20 sex- and age-matched healthy volunteers were included. Salivary cystatin S levels were assessed by Western Blot analysis using a stain-free technology. The expression of miR-126, miR-335-5p and CST4 was assessed by qPCR in 15 MSG biopsies differing for USFR and MSG/FS. Results: We found that salivary cystatin S was significantly decreased in pSS patients vs HV (p=0.000) especially in those with hyposalivation. A positive correlation was observed between cystatin S and USFR (r=0.75, p=0.01). Salivary cystatin S was also significantly reduced in patients with a SGUS score ≥2 in submandibular glands. The expression levels of miR-126 and miR-335-5P increased in inverse proportion with USFR. The mRNA of CST4 did not change significantly, suggesting a post-trascriptional regulation. Conclusions: Cystatin S represents a promising biomarker for pSS strongly correlated with glandular dysfunction. An up-regulation of miR-126 and miR-335-5P might be implicated in its expression.