New blood markers may help diagnose Sjögren’s when antibodies are absent

A panel of four blood markers may help identify people with Sjögren’s disease, even those who lack common disease-associated antibodies, a new study finds.

Researchers also identified blood marker panels linked to overall disease activity and involvement of specific organs. Although more studies are needed to confirm the results, the scientists said these findings could help improve diagnostics for Sjögren’s.

The study, “Discovery of biomarkers for primary Sjögren’s syndrome based on multi-omics data, construction of diagnostic models, and clinical correlation analysis,” was published in Arthritis Research & Therapy.

Recommended Reading

Sept. 30, 2026 News by Marisa Horak, MS

Experimental therapy rapidly lowers disease activity in Sjögren’s trial

Challenges in diagnosing Sjögren’s without typical antibodies

Sjögren’s is an autoimmune disorder that mainly affects the glands that produce saliva and tears, leading to dry mouth and dry eyes. However, the disease can also damage other parts of the body, causing a wide range of symptoms.

Many people with Sjögren’s have antibodies that mistakenly attack the body’s own tissues. Two common types are anti-Ro (SSA) and anti-La (SSB) antibodies. Testing for these antibodies can help doctors diagnose Sjögren’s.

However, as many as half of all people with Sjögren’s may lack these common antibodies. Such patients are considered seronegative, making an accurate diagnosis more challenging. Scientists are working to identify other markers that could lead to faster, more reliable diagnoses for these patients.

“It is essential to develop reliable diagnostic biomarkers for evaluating seronegative [Sjögren’s],” the researchers wrote.

A team led by scientists in China set out to identify blood markers that might help detect Sjögren’s, especially in seronegative patients. They used two approaches: metabolomics, which examines small molecules involved in the body’s chemical processes, and lipidomics, which studies fats and related molecules. They then used artificial intelligence (AI) models to identify patterns among these potential markers.

Four blood markers show promise for identifying Sjögren’s

The researchers initially analyzed blood samples from 154 people with Sjögren’s and 50 healthy people without the disease. They identified 65 metabolites and 63 lipids (fats and related molecules) that were significantly associated with Sjögren’s.

Using AI models, the researchers selected four molecules — threo-9,10-Dihydroxystearic acid, sphingosine-1-phosphate, LPC 20:0:0, and Cer 34:1;O2 — that together formed a distinctive pattern associated with Sjögren’s.

To assess how well this four-molecule pattern could distinguish people with Sjögren’s from those without it, the researchers used a measure called the area under the receiver operating characteristic curve (AUC). AUC values range from 0 to 1, with values closer to 1 indicating a greater ability to distinguish between groups.

The four-molecule pattern distinguished people with Sjögren’s from healthy controls with an AUC above 0.99. It performed similarly in distinguishing seronegative patients from healthy controls, also with an AUC above 0.99.

“These results highlight the important role of [blood] metabolites in the early diagnosis and clinical prediction of [seronegative Sjögren’s patients],” the researchers wrote.

The researchers then tested the four-molecule pattern in an independent group of 48 people with Sjögren’s and 25 healthy controls. The pattern again showed a strong ability to distinguish patients from healthy controls, with AUCs of 0.98 for all Sjögren’s patients and 0.97 for seronegative patients.

The validation group also included 60 people with xerostomia (dry mouth) who did not meet the study’s classification criteria for Sjögren’s and had no other systemic autoimmune diseases. The four-molecule pattern also distinguished people with Sjögren’s, including seronegative patients, from those with xerostomia, with AUCs above 0.91.

More research needed before blood marker panel can be used in clinics

The researchers noted that the study involved a relatively small number of patients at a single center. The cost of molecular testing may also make it difficult to use the four-molecule panel widely. They called for further research to confirm their results.

The researchers also used their metabolomic and lipidomic data to look for links between blood molecules and clinical features in people with Sjögren’s.

They identified several potential links. For example, a 12-molecule panel was significantly associated with disease activity, as measured by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). The team also identified a three-molecule pattern associated with lung involvement and a five-molecule pattern associated with blood-related abnormalities.

“Our findings indicate that overall [Sjögren’s] disease activity, as assessed by the ESSDAI, correlates with a distinct [blood] metabolic profile,” the researchers wrote. “Moreover, this global profile can be further resolved into characteristic metabolic signatures that correspond to involvement of specific organ systems.”

Blood marker profiles also varied by age, sex, and anti-SSA antibody status. These findings could help researchers better understand the biological processes involved in Sjögren’s.

“Our study not only provides deeper insights into the metabolic dysregulation of [Sjögren’s] but, more importantly, paves the way for novel metabolomics-based precision diagnostics,” the scientists wrote. “Future research, involving larger longitudinal [studies] and functional experiments to validate the mechanisms of key metabolites, holds promise for identifying new therapeutic targets and ultimately advancing [Sjögren’s] management into an era of personalized medicine.”