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    4 biomarkers may improve Sjögren's syndrome treatment

     

    Greater CTSS activity

    The investigators found that tear CTSS activity was 6 times as great in patients with Sjögren’s syndrome as in those with rheumatoid arthritis and 8 times as great as in patients with other autoimmune diseases. However, levels of the three other tear proteins were reduced in in Sjögren’s patients compared to the other two groups.

    sIgA was 6-fold lower in Sjögren’s syndrome patient tears compared to tears from those patients with rheumatoid arthritis or other autoimmune diseases, LF was 5-fold lower in Sjögren’s syndrome patient tears than in rheumatoid arthritis patient tears and 8-fold lower than in tears of those patients with other autoimmune diseases. CysC was 4-fold lower in Sjögren’s syndrome patient tears than in rheumatoid arthritis patient tears and 6-fold lower than in tears of those patients with other autoimmune diseases.

    Because CysC regulates CTSS in an equimolar fashion, higher levels of CysC result in lower activity of CTSS and vice versa.

    “If you see the concentration levels of CTSS go up in the tear film, while the CysC levels go down, that probably means that the capability of CysC to regulate the CTSS activity as it does in the tear film of normal patients is disrupted,” Dr. Edman pointed out.

    The researchers continue to study these mechanisms in a mouse-disease model, further exploring the hypothesis that both an increase in the gene expression of CTSS in the lacrimal glands and its increased recovery in secretory granules in tears, as well as the decrease in CysC, are involved in increased disease activity.

    They also are exploring whether these proteins may not be just passive biomarkers of Sjögren’s syndrome but may reflect the level of inflammation of the lacrimal gland.

    “It’s both a decrease in the ratio and an increase in the protein abundance,” Dr. Hamm-Alvarez outlined. “We go back and forth between the studies where we are identifying the biomarkers and then trying to figure out what does that illustrate about defective function in the glands. We’re very interested in using the biomarkers diagnostically, but then trying to deduce changes in molecular function that represent opportunities to intervene or to restore function.”

    Confirming the relationship

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