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Kavita Renduchintala, Starleen E. Whitt, Srikanth Janga, Mihir Shah, Martin Heur, John Irvine, Daniel Arkfeld, Wendy J. Mack, William Stohl, Sarah F. Hamm-Alvarez; Tear-Derived Cathepsin S Activity as a Novel Diagnostic Marker for Sjögren's Syndrome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4240.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the utility of Cathepsin S (CATS) as a biomarker for diagnosing Sjögren’s Syndrome (SjS), CATS levels in the tears of patients with SjS were compared to CATS levels in patients with other forms of autoimmune diseases and keratoconjuctivitis sicca (KCS). Current markers utilized for diagnosis of SjS include SSA/SBB autoantigens; however, these markers lack sensitivity and specificity in unequivocally diagnosing SjS.
111 patients were recruited. Schirmer’s tests were administered to 41 patients diagnosed with primary or secondary SjS, 23 patients with Rheumatoid Arthritis (RA) without secondary SjS, 17 patients with Systemic Lupus Erythematosus (SLE) without secondary SjS, 20 patients with other autoimmune diseases without secondary SjS, and 10 patients with KCS. Schirmer’s strips were placed on ice after tear collection. Tear proteins were subsequently eluted and analyzed within 4 hours for CATS activity using the BioVision Cathepsin S Activity Assay Kits with Ac-Val-Val-Arg-7-Amino-4-trifluoromethylcoumarin as substrate. Protein content of the tears was measured using the Bio-Rad assay and CATS activity was expressed as normalized to protein content. SSA and SSB levels were also measured in blood from autoimmune disease patients.
The mean CATS activity/tear protein values, expressed below as RFU/20 µg tear protein, were determined for each group and statistically compared by t-tests. The CATS activity value for SjS was 7945.4 ± 1045.3, significantly elevated compared to 3727.8 ± 923.9 for RA (p =.003), 2852.4 ± 534.3 for SLE (p=.00003), and 2624.56 ± 914.7 for KCS (p=.0003). Patients with primary SjS (n=11) averaged 9063.4 ±1932.3 in comparison to patients with secondary SjS (n=30) who averaged 7535.4 ± 972.8 (p=0.41). Within the diagnosed SjS patients group, CATS activity for SSA+/SSB+ and SSA+/SSB- patients was 9445.1 ± 1335.7, compared to 3485.8 ± 931.6 for SSA-/SSB- patients (p=.001).
CATS tear activity is a potential diagnostic marker for SjS, due to the markedly elevated levels of CATS in tears of SjS patients compared to those in patients with RA, SLE or KCS. A correlation between CATS activity and SSA+ autoantigen is also evident.
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