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Abstract Number: 2194

Cathepsin S Activity in Tears As a Marker of Sjögren’s Syndrome

S.E. Whitt1, K. Renduchintala1, S. Janga2, M. Shah2, J. Zhu3, K. Silka3, S. Bricel3, D. Bach3, M. Heur4, S. Christianakis5, J. Irvine4, D. Arkfeld6, W.J. Mack3, William Stohl7 and S.F. Hamm-Alvarez2, 1University of Southern California Keck School of Medicine -These authors contributed equally to this work, Los Angeles, CA, 2University of Southern California School of Pharmacy, Los Angeles, CA, 3University of Southern California Keck School of Medicine, Los Angeles, CA, 4Doheny Eye Institute, Los Angeles, CA, 5Med/Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, CA, 6Div of Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, CA, 7Division of Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, CA

Meeting: ACR/ARHP Annual Meeting 2012

Keywords: Sjogren's syndrome and biomarkers

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Session Information

Title: Sjögren's Syndrome - Clinical

Session Type: Abstract Submissions (ACR)

Background/Purpose:   Currently used biomarkers for Sjögren’s Syndrome (SS), such as anti-SSA/Ro or anti-SSB/La, lack sensitivity and specificity.  The goal of the work presented here is to evaluate the association of elevated Cathepsin S (CATS ) with SS and contrast this to CATS associations with other autoimmune or dry eye disorders.

Methods: Patients were recruited from outpatient Rheumatology and Ophthalmology clinics. Schirmer’s tests were administered to patients with primary or secondary SS (n=47), rheumatoid arthritis (RA) without SS (n=41), systemic lupus erythematosus (SLE) without SS (n=18), other autoimmune diseases without SS (n=10), non-autoimmune dry eyes (n=13), and blepharitis (n=8). The Schirmer’s strips were immediately placed on ice after tear collection, and tear proteins were eluted and analyzed within 4 hours for CATS activity using commercial assay kits. CATS activity was normalized to protein concentration.  Serum positivity for anti-SSA and anti-SSB in autoimmune disease patients was determined by a clinical laboratory.

Results: CATS data were log-transformed prior to analysis to deemphasize outlier values.  To compare log CATS activity among patient groups accounting for correlated data (correlation among eyes), generalized estimating equations were used. Median CATS activity in SS patients (median 5140) was compared to non-SS patient groups: SS vs. RA (median 1476, p=<.00001), SS vs. SLE (median 2226,  p=.0008), SS vs. Blepharitis (median 1770, p=.022), SS vs. Dry Eye (median 2768, p=.003), and SS vs. Other (median 1770, p=.013).  CATS activity did not significantly differ (p=0.31) between primary SS (n=11; median 5514) and secondary SS (n=36; median 4970). Anti-SSA-positive SS patients (n=30; median 3288) and anti-SSA-negative SS patients (n=8; median 1732) also did not significantly differ on CATS activity (p=0.29). The data did not demonstrate a significant difference (p=0.25) in median CATS activity between SSB-positive (n=13; median 5321) and SSB-negative (n=25; median 4456) groups.

Conclusion: Normalized CATS activity is significantly greater in the tears of SS patients than in the tears of patients with non-SS autoimmune or non-autoimmune diseases. Determination of CATS activity in tears may be clinically useful by shortening the lag time in diagnosing patients with SS, thereby promoting earlier initiation of appropriate therapy. The simplicity of the test may permit its automation and use in real-world clinical settings.


Disclosure:

S. E. Whitt,
None;

K. Renduchintala,
None;

S. Janga,
None;

M. Shah,
None;

J. Zhu,
None;

K. Silka,
None;

S. Bricel,
None;

D. Bach,
None;

M. Heur,
None;

S. Christianakis,
None;

J. Irvine,
None;

D. Arkfeld,
None;

W. J. Mack,
None;

W. Stohl,
None;

S. F. Hamm-Alvarez,
None.

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