Sjögren’s protein score may help measure salivary gland inflammation
Study: New blood test could eliminate need for a biopsy
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The “Sjögren’s protein score,” a newly identified blood protein signature of Sjögren’s disease, may help doctors measure inflammation inside the salivary glands without the need for a biopsy, a new study suggests.
Results from the blood test, based on a group of 16 immune-related proteins, reflected local glandular inflammation and correlated with disease manifestations in other organs, genetic risk factors, and self-reactive antibodies associated with Sjögren’s.
“The correlation between the ‘Sjögren protein score’ and [tissue] inflammation in minor salivary glands suggests that a [blood-based] proxy score could serve as an alternative to tissue biopsies in disease assessment,” researchers wrote.
The study “A proteomic profile correlates with salivary gland inflammation and disease-associated antibodies in Sjögren’s disease,” was published in the Annals of the Rheumatic Diseases.
Reliable biomarkers needed to understand Sjögren’s, guide therapy
Sjögren’s is a complex disease characterized mainly by inflammation and functional impairment of glands that produce saliva and tears. While dryness of the mouth and eyes are the most common symptoms, the disease can also affect multiple other tissues and organs. In some cases, it can lead to lymphoma, a type of blood cancer.
Researchers have developed tools to group Sjögren’s patients by symptoms, which may help identify who is more likely to benefit from specific treatments. But reliable biological markers are still needed to understand the disease and guide therapy.
“Objective biomarkers are needed to detect [disease-causing] mechanisms at play in individual patients, and to discover or follow molecular targets of new treatments,” wrote a team led by scientists at the Karolinska Institutet in Sweden, who set out to identify protein biomarkers indicative of salivary gland inflammation in Sjögren’s.
The team first measured protein levels in paired salivary gland biopsy samples and blood samples from 81 adults with Sjögren’s and 19 age- and sex-matched individuals with sicca (dryness of the eyes and mouth) but without Sjögren’s.
The analysis of paired samples revealed more pronounced differences in salivary gland tissue than in blood between Sjögren’s patients and healthy controls. Several proteins were found at particularly high levels in the glands of Sjögren’s patients, including CXCL13, a protein that plays a key role in guiding certain immune cells to sites where they are needed.
Other inflammation-related proteins, including CXCL10, were significantly elevated in both blood and gland tissue from patients compared with controls.
Levels of some proteins were associated with specific organs
To confirm these findings, the team analyzed blood samples from two larger groups: a discovery group comprising 456 adults with Sjögren’s and 141 healthy controls, and a replication group of 233 Sjögren’s patients and 137 controls.
They found 27 proteins at significantly different levels in the blood of Sjögren’s patients compared with controls. Of these, 16 were validated in the replication group. The most significant protein changes involved the proteins Gal9, CXCL13, PDCD1, CCL19, and LAG3.
Analyses to identify potential links between these proteins and disease manifestations not involving glands (extraglandular manifestations) showed that higher blood CXCL10 levels were associated with swollen lymph nodes, skin symptoms, biological abnormalities, lung involvement, and lymphoma.
Levels of some proteins were associated with specific organs: elevated CD8A and CD27 were linked to kidney involvement alone, while higher LAG3 was associated with more biological abnormalities. Those with lung involvement showed increases in many inflammation-related proteins, and all proteins related to lymphoma were also tied to lung involvement.
The novel [Sjögren protein score] appears promising as a biomarker to indicate the inflammatory status of target tissue.
When patients were grouped based on the presence of self-reactive antibodies frequently associated with Sjögren’s, such as ANA, anti-Ro (SS-A), and anti-La (SS-B), blood levels of the validated 16 proteins increased gradually across these groups. Specifically, they were lowest in people without ANA antibodies, higher in ANA-positive patients, and highest in those who were double-positive for SS-A and SS-B.
A similar pattern was seen in salivary gland tissue, “indicating that the inflammatory environment of the [salivary gland samples] is mirrored in the circulation,” the researchers wrote.
Blood levels of certain proteins closely matched those in gland tissue. CD33 showed the strongest association, followed by LAIR2, meaning that the two proteins may reflect disease activity in both tissues.
Finally, the scientists developed a new blood-based biomarker, the ‘Sjögren protein score,’ based on the 16 key proteins. The score rose as salivary gland inflammation became more severe, suggesting it could reflect what’s happening inside the glands — without the need for a biopsy.
Sjögren’s patients across all antibody groups, even those testing negative for all three antibodies, showed significantly higher scores relative to healthy people. Higher scores were also associated with rheumatoid factor (another self-reactive antibody), elevated blood antibody levels, and abnormal salivary gland ultrasound findings.
Overall, the Sjögren protein score discriminated Sjögren’s patients from healthy individuals with an accuracy of 88.8%.
“The data of the present study shed further light on the dysregulated [protein set] in SjD [Sjögren’s disease] in relation to extraglandular manifestations,” the researchers wrote. “The novel ‘Sjögren protein score’ appears promising as a biomarker to indicate the inflammatory status of target tissue and also distinguishes patients with anti-Ro/La autoantibody-negative SjD from controls.”
