Research Points to Protein in Saliva as Possible Biomarker for Sjögren’s

Levels of the siglec-5 protein in saliva are significantly higher in Sjögren’s syndrome patients than in healthy people or patients with systemic lupus erythematosus (SLE), and correlate with the severity of disease symptoms, suggesting that the protein could serve as a salivary biomarker for the diagnosis of Sjogren’s syndrome.

The study with the findings, “Soluble siglec-5 is a novel salivary biomarker for primary Sjogren’s syndrome,” was published in the Journal of Autoimmunity.

Dryness of the eyes and mouth are a hallmark of Sjögren’s syndrome, a chronic autoimmune condition where immune cells infiltrate and damage certain glands in the body, such as those producing tears and saliva.

Current methods for diagnosing the condition focus on identifying the presence of specific disease autoantibodies, measuring eye integrity as well as tear and saliva production, and doing biopsies.

Although accurate, most of these measures are not available in typical health centers, highlighting the need for good biomarkers — easily measured in blood or saliva — that help diagnose the condition.

Aiming to identify potential Sjögren’s syndrome biomarkers, researchers in South Korea examined different proteins in the blood and saliva of Sjögren’s syndrome patients, and compared them with  levels seen in healthy controls, patients with eye and mouth dryness not caused by Sjögren’s, and SLE patients.

First, they found that the gene holding the instructions for the siglec-5 protein was highly active in Sjögren’s syndrome patients, but no differences in protein levels were seen inside the cells.

They next compared the levels of soluble siglec-5 in the blood and saliva, and found that although blood siglec-5 was higher in SLE patients, the Sjögren’s patient group had the highest levels of the protein in the saliva.

Interestingly, salivary levels of siglec-5 in Sjögren’s patients correlated with lower salivary flow rates, increased damage to the ocular surface, and higher levels of autoantibodies, all of which indicate disease severity.

“To the best of our knowledge, this is the first report that siglec-5 could serve as a novel biomarker that can be measured from non-invasively obtainable samples such as saliva,” researchers said.

The investigators then tested the potential biomarker using a validation cohort consisting of 90 subjects with symptoms similar to those of Sjögren’s syndrome, 45 of whom were later diagnosed with the disease. Salivary siglec-5 showed mixed results.

The patients in this cohort had only mild symptoms. Therefore, it is possible that the marker would work better in individuals with more advanced disease.

“Because this biomarker correlates with [unstimulated salivary flow rate] and [damage to the ocular surface], salivary siglec-5 measurement will at a minimum provide more evidence to support patient diagnosis in clinics where the standard tests are not available,” the authors stated.

Further studies are necessary to understand how siglec-5 is related to the symptoms of Sjögren’s syndrome and how it could be implemented as a biomarker in clinical practice.

However, the researchers concluded that “although the mechanistic details of siglec-5 contribution to gland dysfunction remain unclear, this easily obtained salivary biomarker may provide benefits for the diagnosis of [Sjögren’s syndrome].”