Blood molecule may offer new way to detect and track Sjögren’s disease
High levels of hsa-miR-661 linked to more severe disease activity
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A molecule that helps control how genes work, called hsa-miR-661, may help doctors diagnose primary Sjögren’s disease and could one day become a treatment target, according to a study from China.
Researchers found that levels of hsa-miR-661 were significantly higher in circulating immune cells taken from people with primary Sjögren’s than from healthy volunteers. Among patients, higher levels were linked with more active or severe disease.
Hsa-miR-661 levels enabled researchers to accurately distinguish people with and without Sjögren’s, as well as those with more or less active disease.
Study links higher hsa-miR-661 levels to greater disease activity
“These findings suggest [hsa-miR-661’s] potential as a diagnostic biomarker and therapeutic target in [primary Sjogren’s disease],” the researchers wrote, while noting that further studies are needed to confirm both the molecule’s predictive potential and its role in disease development.
The study, “Analyzing the expression of hsa-miR-661 in peripheral blood mononuclear cells of patients with primary Sjögren’s syndrome and its clinical significance,” was published in Clinical Rheumatology.
Sjögren’s is an autoimmune condition marked by abnormal immune responses that mainly target the body’s moisture-producing glands, leading to hallmark Sjögren’s symptoms such as dry eyes and dry mouth.
For some people, Sjögren’s occurs associated with other underlying conditions, in which case it is known as secondary Sjögren’s. However, the cause of primary Sjögren’s — when the disease develops on its own — is not fully understood.
Growing evidence suggests that microRNAs (miRNAs), small strands of genetic material that help regulate gene activity, may play a role in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus, the most common form of lupus.
Altered miRNA patterns have already been found in tears and salivary-gland tissue from people with primary Sjögren’s. However, “the role of hsa-miR-661 remains largely unexplored,” the researchers wrote.
Researchers compare blood from people with and without Sjögren’s
To investigate this further, researchers in China measured hsa-miR-661 levels in circulating immune cells from 58 people with primary Sjogren’s and 58 healthy people of similar age and sex (the control group). They also examined whether hsa-miR-661 levels were linked with clinical symptoms or lab findings in patients.
All participants were recruited from the General Hospital of Ningxia Medical University between September 2021 and September 2022. Most patients were women (96.6%), with an average age of about 48.53 years (range 29-69).
The researchers found that hsa-miR-661 levels were significantly higher in people with primary Sjögren’s than in healthy controls. Patients were then divided into two equal groups — 29 with higher levels and 29 with lower levels — based on the median value.
Clear differences emerged between the two patient groups. Those with higher hsa-miR-661 levels were significantly more likely to be age 40 or older and to have had the disease for 10 years or longer, “suggesting a possible association with disease progression,” the researchers wrote.
Participants with higher hsa-miR-661 levels also showed signs of greater immune and inflammatory activity. They had lower levels of complement C3 — which can indicate higher immune-system activation — and higher erythrocyte sedimentation rate (ESR), a common marker of inflammation.
Both low C3 and high ESR “are clinical indicators of disease activity and prognosis in” primary Sjögren’s, with low C3 being “particularly recognized as a marker of poor outcomes,” the researchers wrote.
Higher hsa-miR-661 linked to stronger immune activity, worse symptoms
People with higher hsa-miR-661 levels reported significantly more severe dry-mouth symptoms. However, the researchers did not find a clear link between hsa-miR-661 levels and dry eye severity or most other symptoms.
Higher hsa-miR-661 levels were also significantly linked to higher scores on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), meaning patients with more of this molecule generally had more active disease.
Statistical analyses showed that hsa-miR-661 levels could distinguish people with primary Sjögren’s from healthy individuals with 89.2% accuracy and identify patients with more active disease versus milder disease with 79.9% accuracy.
The researchers then explored how hsa-miR-661 might contribute to disease biology. They found that a molecule called circRNA_0008301 can bind to hsa-miR-661 and influence how much of it is available in cells. They also reported that hsa-miR-661 may target TOLLIP, a protein that normally helps regulate immune activity.
According to the researchers, higher levels of hsa-miR-661 may weaken TOLLIP’s protective role, leading to increased inflammation and ongoing immune activity — key features of disease development. In this setting, circRNA_0008301 may help limit that effect by “mitigating miR-661-mediated suppression and helping preserve immune balance,” the team wrote.
Overall, the results support hsa-miR-661’s “potential as a reliable biomarker for both diagnosis and disease monitoring,” and point to its possible role as a “therapeutic target” in primary Sjögren’s, the researcher wrote.
However, the researchers stressed that larger, multi-center studies are needed to confirm these findings and to determine whether modulating hsa-miR-661 levels could offer a novel therapeutic approach.
