CXCL9 may be biomarker for primary Sjögren’s with extra-glandular symptoms
Signaling molecule is involved in migration, maturation of lymphocytes
Patients with primary Sjögren’s syndrome who have extra-glandular symptoms have higher levels of the chemokine CXCL9 than those only affected in the saliva and tear-producing glands, a study finds.
CXCL9 is a small signaling molecule involved in the migration and maturation of lymphocytes, a type of immune cell thought to be involved in developing Sjögren’s.
“This suggests that biomarker CXCL9 may … potentially serve as a helpful indicator for assessing both disease activity and progression in individuals with [primary Sjögren’s syndrome],” the researchers wrote in “CXCL9 may serve as a potential biomarker for primary Sjögren’s syndrome with extra-glandular manifestations,” which was published in Arthritis Research & Therapy.
Sjögren’s syndrome is a chronic autoimmune disease that primarily affects the glands that produce tears and saliva, causing symptoms like dryness in the eyes and mouth.
About 40% of patients have symptoms that affect other tissues and organs, including the joints, skin, lungs, kidneys, and nervous system. These patients have a worse prognosis than those with only glandular involvement.
Studies have shown the salivary glands of patients with primary Sjögren’s — a form of the disease that’s not associated with another health condition and has no clear cause — have a unique profile of chemokines, compared with healthy people. Chemokines are small signaling proteins that control the movement and maturation of lymphocytes, immune cells thought to be involved in the disease’s development.
CXCL9 as measure of primary Sjögren’s disease severity
Here, researchers studied potential biomarkers associated with primary Sjögren’s syndrome, particularly the disease’s extra-glandular symptoms, and analyzed and compared the gene activity profile of 63 patients with primary Sjögren’s, including 50 with extra-glandular involvement, and 12 people without the disease.
Those with extra-glandular symptoms had higher levels of inflammation indicators, antinuclear antibody, and rheumatoid factors than those without these manifestations. They also had higher values in the EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI), meaning more severe disease.
When comparing people with Sjögren’s and those without the disease, researchers found 725 genes that were differentially expressed, most of which (96.1%) were upregulated, or more active, in patients. From these, CXCL9 had the higher difference in activity. When comparing patients with or without extra-glandular involvement, investigators found 727 genes with a significant differential expression. Of these, 517 were upregulated in extra-glandular involvement patients and included CXCL9.
In people with primary Sjögren’s, the genes upregulated were related to lymphocyte differentiation and proliferation, and chemokine/cytokine signaling. Similarly, a number of immune-related pathways were enriched in those with extra-glandular manifestations.
Among the top 20 genes differentially expressed with extra-glandular manifestations, CXCL9 showed the strongest correlation with clinical parameters, including ESSDAI score, erythrocyte sedimentation rate, and immunoglobulin G (IgG), all indicators of inflammation. Plus, those with extra-glandular involvement had higher CXCL9 in the blood than patients without extra-glandular involvement. These levels significantly correlated with the ESSDAI score and IgG levels.
“Overall, these findings confirm that CXCL9 is elevated in [primary Sjögren’s patients], particularly those with [extra-glandular symptoms],” the researchers wrote. “The way it is expressed may be a useful biomarker for measuring disease severity, suggesting that it could have a significant impact on the development of the disease. It could also be utilized as a biomarker or treatment target, but additional research is necessary to validate and fully understand these discoveries.”
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