July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Tear biomarkers for Sjögren Syndrome
Author Affiliations & Notes
  • Sarah F Hamm-Alvarez
    Ophthalmology, Univ of Southern California, Los Angeles, California, United States
    Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Sarah Hamm-Alvarez, None
  • Footnotes
    Support  NIH EY011386
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3287. doi:
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      Sarah F Hamm-Alvarez; Tear biomarkers for Sjögren Syndrome. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3287.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Presentation Description : Sjögren’s syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and loss of function of lacrimal and salivary glands. In addition to the severe dry eye and dry mouth, constitutional symptoms are common. Onset of sicca and systemic symptoms does not always occur in parallel, making diagnosis a challenge. Many signs and symptoms of SS are also associated with other diseases. The lack of specificity of currently-used biomarkers combined with the invasiveness of the salivary gland biopsy used for diagnosis have prompted efforts to identify new non-invasive biomarkers for diagnosis. Our focus is identification of tear biomarkers. Initial leads were generated utilizing the male NOD mouse model, which spontaneously develops many ocular manifestations including autoimmune dacryoadenitis seen in SS patients. The activity and abundance of the cysteine protease, cathepsin S (CTSS), was significantly elevated in lacrimal glands and tears from diseased male NOD mice relative to healthy control BALB/c mice. Extending these findings in two clinical observational studies with distinct patient cohorts, we found that the tears of SS patients exhibited a significant elevation of CTSS activity relative to tears of patients with other autoimmune diseases (receiver operating characteristic or ROC values of 0.77 and 0.919 in the two cohorts) and relative to non-autoimmune dry eye disease (ROC value of 0.840). CTSS is an intriguing protein with many functions linked to inflammation. Its activity is physiologically regulated by cysteine protease inhibitors called cystatins, of which Cystatin C (Cys C) is the most potent inhibitor. Evaluating Cys C levels in tears in parallel, we found its abundance was significantly reduced relative to tear levels in patients with other autoimmune diseases (ROC value of 0.897) and in patients with non-autoimmune dry eye disease (ROC value of 0.729). Other tear proteins that were significantly decreased in tears of SS patients relative to patients with other autoimmune and eye diseases included lactoferrin and secretory IgA. Neither Cys C, lactoferrin, nor secretory IgA offered the ability to further discriminate SS within the autoimmune disease population beyond that of CTSS activity alone, which remained the strongest tear biomarker of SS. However, the combination of lactoferrin and CTSS added to the ability to discriminate SS from non-autoimmune dry eye disease in our patient cohort.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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