Levels of Signaling Molecules in Tears and Saliva Linked to Symptom Severity, Study Says

People with Sjögren’s syndrome have increased levels of specific signaling proteins in their tears and saliva, which are associated with more severe symptoms of eye and mouth dryness, a study finds.

The study, “Elevated cytokine levels in tears and saliva of patients with primary Sjögren’s syndrome correlate with clinical ocular and oral manifestations,” was published in Nature Scientific Reports.

Chronic dryness of the eyes and mouth, collectively known as sicca symptoms, are common in people with Sjögren’s. These symptoms are caused by the accumulation of immune cells that invade the salivary and tear glands, triggering a sustained inflammatory response.

Investigating the levels of proteins — such as the signaling molecules known as cytokines — that regulate these immune and inflammatory responses may help researchers understand how Sjögren’s syndrome progresses. If specific cytokines are excessively produced in Sjögren’s patients, they also might serve as biomarkers for the disease.

“Identifying protein biomarkers in tear fluid and saliva is desirable when studying local and systemic diseases, as sampling tear fluid and saliva are usually manageable, inexpensive, and non-invasive,” the researchers said.

“[T]he discovery of saliva- and tear-based (…) biomarkers in [Sjögren’s syndrome] will enable their application in disease diagnostics, as well as aid in establishing targeted therapy,” they added.

Norwegian researchers investigated the levels of specific cytokines in the saliva and tears of 29 Sjögren’s patients. They then compared them to those of 20 people with sicca symptoms non-related to Sjögren’s syndrome, and 17 healthy volunteers with no sicca symptoms. None of the participants were using anti-inflammatory medicines at the time of enrollment.

Tear and saliva samples were provided by 19 Sjögren’s patients, 16 non-Sjögren’s sicca controls, and 13 healthy controls. The remaining participants provided samples of either tears or saliva.

Sjögren’s patients were found to have higher levels of 10 different cytokines in their tears than the people with non-Sjögren’s sicca, and the healthy controls. The patients with higher cytokine levels also showed reduced tear production and increased ocular surface damage.

There were two specific cytokines, named IP-10 and MIP-1a, whose levels were particularly elevated in the saliva of Sjögren’s patients when compared with the other groups. Sjögren’s patients had approximately 6-fold higher levels of IP-10 in saliva than healthy controls and non-Sjögren’s patients, and about 3-fold higher salivary MIP-1a than healthy controls.

Interestingly, the increased cytokines in the tears of the Sjögren’s patients were not only inflammatory but also anti-inflammatory, showing that many immune responses take place during disease progression. It is possible that the increased anti-inflammatory response is an effort of the body to reach an equilibrium, the researchers suggested.

“We have demonstrated that upregulated cytokines identified in tear fluid and saliva of [Sjögren’s syndrome] patients show a clear interplay between […] immune responses that may together further contribute to disease pathogenesis,” they said.

Further studies should evaluate if one or some of the cytokines identified in this study might serve as biomarkers of disease progression, the researchers said.