Trio of genes may be new diagnostic markers in Sjögren’s disease: Study
Overactive in people with the disorder, they could also be treatment targets
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Through detailed computer-based analyses of publicly available genetic data sets, a team of scientists in China has identified three genes that are overactive in people with Sjögren’s disease, according to a study.
The scientists are hopeful that, with further validation, these genes may be used as markers to aid in diagnosing Sjögren’s. These overactive genes may also be useful treatment targets for the disease, they said, though they stressed that further work is needed to validate their findings.
“This study provides a foundation for improving [Sjögren’s disease] diagnosis and developing targeted therapies, but … clinical validation and functional studies are essential for translation into practice,” researchers wrote.
The study, “Identification of molecular diagnostic markers and potential therapeutic drugs for Sjögren’s syndrome,” was published in Scientific Reports.
Vaiability makes Sjögren’s tough to diagnose accurately
Sjögren’s is an autoimmune disorder typically characterized by inflammation of the salivary glands and tear ducts, leading to symptoms such as dry mouth and dry eyes. The disease, which predominantly occurs in women, can also affect other systems throughout the body, leading to a wide range of possible disease manifestations.
Because Sjögren’s is so variable, it is often challenging for doctors to accurately diagnose the disease. As there isn’t any one test that can reliably detect Sjögren’s, patients and clinicians typically need to wade through a large battery of tests to identify disease-typical signs and rule out other potential explanations for symptoms.
Researchers are actively working to identify novel disease markers to improve the speed and accuracy of Sjögren’s diagnosis.
In this study, researchers sought to identify genes that are overactive in Sjögren’s and may therefore serve as useful diagnostic markers. They used publicly available gene activity data sets from different tissues, including the salivary glands and blood, in people with or without Sjögren’s.
Genes much more active in women with disease
The team used advanced computer-based analyses to look for differentially expressed genes, or genes whose activity is consistently increased or decreased across tissue types in people with Sjögren’s relative to those without.
They zeroed in on three genes — EPSTI1, IFI44, and IFIT1 — all known to help regulate immune activity, which is consistent with the idea that they might be dysregulated in an immune disorder like Sjögren’s.
To validate these potential biomarkers, the researchers also collected and analyzed samples from 10 women with Sjögren’s and 10 age-matched women without the disease. They found that these genes were significantly more active in blood cells and salivary gland tissues of women with Sjögren’s.
Activity levels of these three genes also correlated with altered numbers of several immune cells in Sjögren’s patients, which “suggests a functional link: the biomarkers may drive immune cell dysregulation or vice versa,” the researchers wrote. They cautioned, however, that their analysis was not designed to identify cause-and-effect relationships, so more research is needed to clarify the direction of this association.
EPSTI1, IFI44, and IFIT1 are promising candidate diagnostic biomarkers for [Sjögren’s disease], with strong diagnostic efficacy and links to immune dysregulation.
To assess whether these genes might be useful diagnostic markers, the researchers used a statistical test called the area under the receiver operating characteristic curve (AUC).
AUC measures how well a given test (in this case, gene activity levels) can differentiate between two groups (in this case, people with or without Sjögren’s). AUC values range from 0 to 1, with higher values indicating greater discriminative accuracy.
Activity levels of all three genes showed high accuracy in discriminating between people with Sjögren’s and those without, with AUC values of 0.9 for IFI44, 0.89 for EPSTI1, and 0.88 for IFIT1.
In additional computer-based analyses, the researchers found that paeoniflorin — a plant-derived compound used in traditional Chinese medicine — may modulate the activity of these three Sjögren’s-related genes.
These findings suggest that “EPSTI1, IFI44, and IFIT1 are promising candidate diagnostic biomarkers for [Sjögren’s disease], with strong diagnostic efficacy and links to immune dysregulation,” the team concluded, noting again a need for further research to confirm their diagnostic potential. “Paeoniflorin may exert therapeutic effects by targeting these biomarkers, but this requires experimental validation.”
