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    4 biomarkers may improve Sjögren's syndrome treatment

    Take-home: Research on the composition of tears and their secretory processes is generating insights that may lead to earlier detection and treatment of Sjögren’s syndrome.

    Reviewed by Maria C. Edman, PhD, and Sarah F. Hamm-Alvarez, PhD

    Los Angeles—Ongoing research on the secretory processes of lacrimal glands continues to yield findings that may facilitate earlier diagnosis of Sjögren’s syndrome and more effective treatment.

    One of the recent developments is the discovery that four tear biomarkers distinguish patients with Sjögren’s syndrome from patients with other autoimmune diseases, said Sarah F. Hamm-Alvarez, PhD, professor and vice chairman, basic research, Department of Ophthalmology, Roski Eye Institute, University of Southern California, and professor of pharmacology and pharmaceutical sciences (secondary), USC School of Pharmacy.

    For more than 20 years, Dr. Hamm-Alvarez and colleagues have focused their research on the process of secretion by the lacrimal glands, which are affected by Sjögren’s syndrome. The team has studied molecular processes for sorting and release of proteins, how these processes go awry, and therapeutic development by targeting anti-inflammatory agents to the glands and the tears.

    The focus has shifted increasingly to Sjögren’s syndrome, specifically the defects in the secretory process that may emerge early in the disease and characterize the diseased lacrimal gland, according to Dr. Hamm-Alvarez.

    About 10 years ago, the researchers discovered in a mouse model of Sjögren’s syndrome that the protein cathepsin S (CTSS) was increased significantly in the tears and lacrimal glands. Moving the work to the clinic, they found that CTSS levels were also elevated in the patients with Sjögren’s syndrome. These findings were published in 2014.

    The new findings

    In 2015, Dr. Hamm-Alvarez, Maria C. Edman, PhD, research associate, USC Roski Eye Institute, and team released new findings on tear biomarkers that may help diagnose patients with Sjögren’s syndrome.

    “We were very interested to begin with CTSS, a protease that is usually present in the lysosomes and helps to degrade proteins,” Dr. Edman said. “Given that we were studying the trafficking processes, we were very curious why the CTSS ended up in the tears of Sjögren’s syndrome mice and also in the tears in the Sjögren’s syndrome patients.”

    After finding alterations in the trafficking processes for this protein, the researchers expanded their study to other proteins present in the tear film that also might serve as biomarkers: secretory IgA (sIgA), lactoferin (LF), and cystatin C (CysC).

    Secretory IgA is the main antibody in the tear fluid and is very active in the defense of mucosal membranes, while LF is decreased in tears of patients with both non-Sjögren’s syndrome dry eye and Sjögren’s syndrome-mediated dry eye. CysC was chosen as the third marker because it is an active inhibitor of CTSS and could be used to detect any shift in the balance between it and CTSS, Dr. Edman explained.

    Female patients with primary or secondary Sjögren’s syndrome (n=28), rheumatoid arthritis (n=31), or other autoimmune disease (n=31) were recruited for the study. An anesthetized Schirmer’s test was performed on both eyes of each patient, followed by analysis for CTSS activity and concentrations of the three other proteins.

    Greater CTSS activity

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