Biomarkers of Interstitial Lung Disease in Sjögren’s Syndrome Identified in Study

KL-6 levels, disease duration were key parameters tied to lung involvement

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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An illustration of lungs struggling to breathe.

Age, disease duration, and blood levels of inflammatory markers Krebs von den Lungen-6 (KL-6) and TNF-alpha are the most discriminating factors for identifying Sjögren’s syndrome patients with interstitial lung disease, a study found.

While less significantly associated, other inflammatory markers, including immunoglobulin M (IgM), c-reactive protein (CRP), eotaxin, and TGF-alpha, could also indicate lung involvement.

Finding any of these potential biomarkers in the clinic should “prompt the search for occult as well as clinically evident lung involvement,” in Sjögren’s patients, the researchers wrote.

The study, “Biomarkers of interstitial lung disease associated with primary Sjögren’s syndrome,” was published in the European Journal of Medical Research.

Interstitial lung disease (ILD) describes a group of conditions marked by inflammation and scarring of lung tissue, leading to shortness of breath and dry cough. It’s common among primary Sjögren’s patients, in whom it’s linked to a worse prognosis.

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But not all patients have symptoms of the lung disorder and screening for it in a chest CT scan isn’t standard practice, meaning a diagnosis and treatment may be delayed significantly.

“Therefore, identifying clinical risk factors and other serum [blood] protein biomarkers associated with the development of [primary Sjögren’s]–ILD will be critically important in facilitating non-invasive detection of lung involvement at earlier, more treatable stages of disease,” the researchers wrote.

In this study, researchers looked for ILD risk factors among 69 patients with primary Sjögren’s who enrolled at one of two clinics in China between September 2013 and June 2017.

Most (84%) were female, with a mean age of 55 at diagnosis. Among the total, 34 met the clinical criteria for definitive ILD, including 19 with advanced and 15 with mild to moderate lung disease. The remaining 35 did not meet the criteria; 25 had indeterminate ILD and 10 showed no signs of it.

The mean age at diagnosis was significantly higher among those with ILD than those without it (61 vs. 52).

ILD patients also had significantly higher levels of circulating IgM antibodies, a class of infection-fighting antibodies in the blood. Molecules indicative of inflammation, including CRP, KL-6, eotaxin, TGF-alpha, and TNF-alpha were also significantly elevated in ILD patients. KL-6 levels and disease duration were key parameters associated with lung involvement in patients, a final statistical analysis found.

Based on these findings, the team developed a clinical prediction model to distinguish Sjögren’s patients with ILD from those without it. Ultimately, this model showed that a combination of age, KL-6, and TNF-alpha levels could identify patients with lung disease with high sensitivity and specificity. Sensitivity refers to the model’s ability to identify patients who truly have ILD, while specificity is its ability to correctly identify those without it.

Several features identified in this study have been previously linked to ILD in Sjögren’s, including age, disease duration, KL-6, and CRP, the team noted.

KL-6 has been identified as a biomarker of lung involvement and severity of lung disease in other autoimmune conditions, including systemic sclerosis and rheumatoid arthritis.

Its ability to distinguish ILD in these patient groups “demonstrates its value as a biomarker for these disorders,” the researchers wrote, noting that whether it’s simply an indicator of cell damage or plays an active role in it remains to be determined.

Despite being limited by a small number of patients, and a lack of lung function tests, the research team said its “findings support the association between [primary Sjögren’s]–ILD and serum protein biomarkers,” the researchers wrote.

“Prospective studies will also be important to investigate a wider range of biomarkers and their ability to correlate with disease activity over time,” the researchers wrote. “In turn, these corroborative studies will provide greater insight to the underlying pathogenesis of [primary Sjögren’s]–ILD and elucidate therapeutically targetable pathways.”