Inflammatory markers in blood may help identify people with Sjögren’s
Study findings could also offer clues about disease activity, gland involvement
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Blood levels of several molecules involved in promoting or dampening inflammation may help distinguish people with Sjögren’s disease from healthy individuals and offer clues about disease activity and gland involvement, according to a small study.
People with Sjögren’s showed significantly higher blood levels of the pro-inflammatory molecules IL-15, MCP-1, TNFRII, and MMP-8, as well as lower levels of the anti-inflammatory IL-1RII molecule, compared with healthy controls. Some of these markers were also found to be significantly associated with certain laboratory and clinical features.
“Further prospective studies in larger and independent [groups of patients] are warranted to validate these findings and to clarify the potential clinical utility of these biomarkers for disease stratification and monitoring,” researchers wrote.
The study, “Distinct molecular profile in Sjögren’s syndrome is associated with disease activity and clinical manifestations,” was published in the journal Scientific Reports.
Reliable biomarkers for Sjögren’s diagnosis, monitoring are lacking
Sjögren’s is caused by an erroneous immune system attack against the body’s healthy tissues that produces self-reactive antibodies and inflammatory signals that mainly damage moisture-producing glands.
While the disease most frequently leads to dry eyes and dry mouth, it can also affect the joints, lungs, kidneys, skin, nerves, blood, and other organs. This wide range of symptoms has made it difficult to predict how the disease will behave in patients.
Self-reactive antibodies are already used in Sjögren’s diagnosis, but reliable biomarkers for diagnosis, monitoring, and patient stratification are still lacking, a team of researchers in Italy noted.
To address this gap, the researchers examined whether levels of 23 blood markers known to be involved in boosting or suppressing inflammation could reveal a disease-specific profile linked to Sjögren’s and its clinical features.
2 molecules emerged as strongest independent predictors of Sjögren’s
They analyzed blood samples from 40 people with Sjögren’s (39 women; mean age, 54.2 years) and 41 age-matched healthy women who served as controls. Most patients (80%) reported dry mouth and dry eyes, 45% had joint symptoms, and 45% had disease involvement beyond the salivary and tear glands.
Data showed that people with Sjögren’s had significantly higher blood levels of IL-15, MCP-1, TNFRII, and MMP-8 — all known to have pro-inflammatory properties — compared with healthy controls. In contrast, levels of IL-1RII, which works by suppressing certain inflammatory responses, were significantly lower in patients.
When the team looked at potential links between these molecules and clinical and laboratory features among people with Sjögren’s, they found that IL-15, previously identified as a potential target in Sjögren’s, was significantly higher in patients with hypergammaglobulinemia, or elevated antibody levels in the blood.
This pro-inflammatory molecule was also significantly elevated in patients with a monoclonal component, a finding that reflects multiplication of a single antibody-producing immune B-cell and that is sometimes detected in Sjögren’s patients.
MCP-1, a signaling molecule that helps attract immune cells into inflamed tissues, was linked with glandular disease. Specifically, higher blood MCP-1 levels were significantly associated with higher focus score values, a measure of immune cell clusters in salivary gland tissue that are a hallmark of Sjögren’s, and more severe dry eyes and mouth.
While Sjögren’s patients showed significantly lower IL-1RII levels, those testing positive for self-reactive antibodies against the La (or SSB) protein — which are commonly found in people with Sjögren’s — had significantly higher IL-1RII levels than those testing negative for such antibodies.
TNFRII, IL-1RII, and MMP-8 emerged as the variables most strongly associated with SjD …, supporting their potential relevance as biomarkers of disease-related immune dysregulation.
The link between Sjögren’s and blood levels of IL-1RII and MMP-8, a protein involved in tissue remodeling during inflammation, was identified for the first time. Still, the researchers found no significant associations between MMP-8 levels and overall disease activity, joint symptoms, or specific organ involvement.
The researchers then conducted statistical analyses adjusted for potential influencing factors to assess which of the five molecules could help distinguish Sjögren’s patients from healthy controls.
TNFRII and IL-1RII emerged as the strongest independent predictors of Sjögren’s.
“These findings highlight the potential utility of these [molecules] as biomarkers for disease classification or risk stratification and align with prior evidence implicating TNF and [IL-1/IL-1RII] signaling pathways in the [development] of SjD [Sjögren’s disease],” the team wrote.
A predictive model accounting for the levels of these molecules showed an area under the curve (AUC) of 0.89. AUC values range from zero to one, with higher values indicating better performance in distinguishing people with a disease from those without it.
Among the study limitations, the researchers cited the study’s small sample size and its single-center nature, as well as the fact that samples were collected at one point in time. That design cannot show whether the markers predict disease progression or change with treatment.
Despite these limitations, “TNFRII, IL-1RII, and MMP-8 emerged as the variables most strongly associated with SjD …, supporting their potential relevance as biomarkers of disease-related immune dysregulation,” the researchers wrote.
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