Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Cathepsin S Activity Measurements in Tears As a Putative Marker of Sjgren's Syndrome.

Zhu1,  Jay, Arkfeld1,  Daniel G., Stohl1,  W., Janga2,  Srikanth R., Heur3,  J. Martin, Irvine3,  John, Hamm-Alvarez2,  Sarah F.

USC Keck School of Medicine, Los Angeles, CA
University of Southern California School of Pharmacy, Los Angeles, CA
Doheny Eye Institute, Los Angeles, CA

Background/Purpose:

Sjögren's syndrome (SjS) is a chronic autoimmune disease characterized by inflammation and destruction of the moisture-producing glands in the body. For 4 million patients in the U.S., this process leads to the landmark symptoms of dry eye and dry mouth as well as many possible systemic complications. Despite the prevalence of SjS, current diagnostic methods remain inexact due to a lack of sensitive and specific testing. It is also difficult to distinguish the autoimmune-mediated keratoconjunctivitis sicca (dry eye) from that associated with other types of dry eye seen extensively in ophthalmology practices. Recent studies performed with non-obese diabetic mice indicated increased expression of the protease, cathepsin S, in the tears and lacrimal glands of this established SjS model1. This study seeks to explore the feasibility of measuring cathepsin S (CATS) in the tears of patients as a prelude to exploring its correlation with clinical manifestations of SjS.

Methods:

Tears were acquired from 173 patients in an all-comers trial conducted in the USC Rheumatology Clinic and the Doheny Eye Institute Cornea Clinic using extraction onto Schirmer's strips. Tear proteins were eluted from the strips and CATS activity was assayed within 4 hrs. of collection and normalized to sample protein. Control studies indicated there was no loss of catalytic activity during this period.

Results:

The average CATS value for all patients in the study was 2142 fluorescence units (FU) per 20 ug of total protein (standard error = 210 FU/20ug protein). The average CATS value for the 8 patients in the study with SjS was 5352 FU/20 ug protein (SE = 1430 FU/20 ug protein), and the average value for all non-SjS patients was 1931 FU/20 ug protein (SE = 198 FU/20 ug protein). This represented a threefold increase for SjS patients over non-SjS patients. The average CATS value for the 57 patients from the rheumatology clinic was 2556 FU/20 ug protein (SE = 410 FU/20 ug protein) while the average CATS value for the 116 patients from the cornea clinic was 1958 FU/protein (SE = 243 FU/20ug protein).

Conclusion:

This study shows the feasibility of measuring the enzymatic activity of biomarker proteins in tear samples collected from patients. In particular, they support the potential of CATS as a biomarker indicative of SjS. A new clinical study is ongoing which further explores the validity of this biomarker in a patient population in which SjS patients as well as patients with non-autoimmune keratoconjunctivitis sicca are more extensively represented.

Reference:

1Li, X, Wu, K & Edman, M, et al. Increased expression of cathepsins and obesity-induced proinflammatory cytokines in lacrimal glands of male NOD mouse. Investigative Ophthalmology and Visual Science. 2010; 51:5010–5029.

To cite this abstract, please use the following information:
Zhu, Jay, Arkfeld, Daniel G., Stohl, W., Janga, Srikanth R., Heur, J. Martin, Irvine, John, et al; Cathepsin S Activity Measurements in Tears As a Putative Marker of Sjgren's Syndrome. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :487
DOI:

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