Longitudinal analysis of tear cathepsin S activity levels in male non-obese diabetic mice suggests its potential as an early stage biomarker of Sjögren’s Syndrome

Abstract

Context: Cathepsin S (CTSS) activity is elevated in Sjögren’s Syndrome (SS) patient tears.

Objective: To evaluate longitudinal expression of tear and tissue CTSS activity relative to other disease indicators in Non-Obese Diabetic (NOD) mice.

Methods: CTSS activity was measured in tears and lacrimal glands (LG) from male 1–6 month (M) NOD and 1 and 6 M BALB/c mice. Lymphocytic infiltration was quantified by histopathology, while disease-related proteins (Rab3D, CTSS, collagen 1) were quantified using q-PCR and immunofluorescence.

Results: In NOD LG, lymphocytic infiltration was noted by 2 M and established by 3 M (p < 0.01). IFN-ɣ, TNF-α, and MHC II expression were increased by 2 M (p < 0.01). Tear CTSS activity was significantly elevated at 2 M (p < 0.001) to a maximum of 10.1-fold by 6 M (p < 0.001). CTSS activity in LG lysates was significantly elevated by 2 M (p < 0.001) to a maximum of 14-fold by 3 M (p < 0.001). CTSS and Rab3D immunofluorescence were significantly increased and decreased maximally in LG acini by 3 M and 2 M, respectively. Comparable changes were not detected between 1 and 6 M BALB/c mouse LG, although Collagen 1 was decreased by 6 M in LG of both strains.

Conclusion: Tear CTSS activity is elevated with other early disease indicators, suggesting potential as an early stage biomarker for SS.

KEYWORDS:

• Cathepsin S
• non-obese diabetic mouse
• lacrimal gland
• Sjögren’s Syndrome
• dacryoadenitis
• autoimmune inflammation

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by NIH grants EY011386 and EY026635 to SHA and in part by an unrestricted grant to the USC Department of Ophthalmology from Research to Prevent Blindness, New York, NY. The authors would like to thank the Translational Research Laboratory in the USC School of Pharmacy for supporting this work. The Cell and Tissue Imaging Core of the USC Research Center for Liver Diseases provided histology services (NIH P30 DK048522).