Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren's Syndrome patients.

Cathepsin S (CTSS) activity is elevated in Sjögren's Syndrome (SS) patient tears. Here we tested whether protease inhibition and cystatin C (Cys C) levels are reduced in SS tears, which could lead to enhanced CTSS-driven degradation of tear proteins. CTSS activity against Cys C, LF and sIgA was tested in SS or healthy control tears. Tears from 156 female subjects (33, SS; 33, rheumatoid arthritis; 31, other autoimmune diseases; 35, non-autoimmune dry eye (DE); 24, healthy controls) were analyzed for CTSS activity and Cys C, LF, and sIgA levels. Cys C and LF showed enhanced degradation in SS tears supplemented with recombinant CTSS, but not supplemented healthy control tears. CTSS activity was significantly increased, while Cys C, LF and sIgA levels were significantly decreased, in SS tears compared to other groups. While tear CTSS activity remained the strongest discriminator of SS in autoimmune populations, combining LF and CTSS improved discrimination of SS beyond CTSS in DE patients. Reductions in Cys C and other endogenous proteases may enhance CTSS activity in SS tears. Tear CTSS activity is reconfirmed as a putative biomarker of SS in an independent patient cohort while combined LF and CTSS measurements may distinguish SS from DE patients.

Measurement of sternal curvature angle on patients with pectus excavatum.

BACKGROUND: Pectus excavatum (PE) is a chest deformity characterized by marked sternal depression. The objective of this study was to quantify the sternal curvature observed in patients diagnosed with PE using the sternal curvature angle (SCA). METHODS: A retrospective review of lateral chest X-rays of patients with PE from 2006 to 2013 was performed. The SCA was measured in a manner similar to the method of Cobb's angle is used to measure spinal curvature. SCA and Haller index were calculated from the chest X-rays for all patients. RESULTS: Lateral chest X-rays of 202 PE and 196 normal control patients were analyzed. The mean SCA ± SD of PE patients was 40.56° ± 12.88° compared to 22.02° ± 7.65° for normal patients. The difference was statistically significant with a p value of <0.0001. No significant concordance between SCA and Haller index measurements in the PE group was found (Kendall τ = -0.00015, p value = 0.9975). CONCLUSION: The difference in sternal curvature as measured by the sternal curvature angle between the pectus excavatum and normal patients was statistically significant. Our data suggest that sternal depression evident in PE patients is not a simple linear depression of the sternum but due to curvature in the sternal body.