Blood Protein Levels May Help ID Hidden Lung Disease in Sjögren’s

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Elevated levels in the blood of the protein Krebs von den Lungen-6 (KL-6) — an indicator of lung inflammation — may help identify interstitial lung disease (ILD) in people with primary Sjögren’s syndrome who may not show symptoms, a study suggests.

“Serum KL-6 level can serve as a valuable biomarker for identifying hidden ILD in patients with newly diagnosed [Sjögren’s],” the researchers wrote, adding that “regular screening may be warranted.”

The study, “KL-6 as a Biomarker of Interstitial Lung Disease Development in Patients with Sjögren Syndrome: A Retrospective Case–Control Study,” was published in the Journal of Inflammation Research.

Interstitial lung diseases, or ILDs, are conditions characterized by inflammation and progressive scarring of lung tissue, leading to shortness of breath and dry cough. These conditions are considered a common complication among people with primary Sjögren’s syndrome.

However, not all Sjögren’s patients with an underlying ILD show clinical symptoms. Thus, easily detectable biomarkers that correlate with disease progression would be valuable in clinics.

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KL-6 is a membrane protein found in several epithelial cells, particularly type 2 pneumocytes — cells of the lung epithelium that are important for innate immune responses. It also has been proposed as a biomarker of ILD.

Now, a team led by researchers at the National Defense Medical Center in Taipei, Taiwan, assessed the role of KL-6 as a potential biomarker of ILD in people newly diagnosed with primary Sjögren’s or pSS.

In total, they conducted a retrospective analysis of data from 39 patients diagnosed with pSS between 2011 and 2018. These patients had a mean age of 57.41 years and the majority (87.2%) were women.

All patients underwent a high-resolution CT scan and had their blood KL-6 levels determined by two different methods. One was an enzyme-linked immunosorbent assay (ELISA), while the other was called LETIA, for latex particle-enhanced turbidimetric immunoassay. Both tests rely on the presence of antibodies that can recognize and bind to KL-6.

Among the patients, 21 (53.85%) ended up developing ILD after a median follow-up of two years.

The median levels of KL-6 measured using ELISA were significantly higher in the ILD group compared with the non-ILD group (median of 1,232 U/mL vs. 764.5 U/mL). Although the same tendency was seen when using LETIA, differences in KL-6 levels between the two patient groups were not statistically significant (median of 329 U/mL in the ILG group vs. 245 U/mL in the non-ILD group).

The levels of KL-6 in the blood did not differ between patients with or without anti-Ro antibodies — a characteristic of Sjögren’s — nor between those with and without cancer. Of note, a total of seven patients, including four in the ILD group and three in the non-ILD group, had a co-existing cancer.

A statistical analysis also revealed that KL-6 levels in the blood — higher than 922 U/ml as measured by ELISA and 402 U/ml as measured by LETIA — were correlated with a significantly higher risk of ILD. Specifically, the risk of ILD was 12 times higher when KL-6 levels surpassed the cut-off value in the ELISA test and 7.3 times higher when using LETIA.

Overall, “serum KL-6 levels were significantly higher in SS patients with developing ILD and might denote early pulmonary damage,” the researchers wrote.

The team noted that ILD “may be highly misdiagnosed or delay-diagnosed in patients with pSS.” Thus, having KL-6 levels as a biomarker could be useful.

“Serum KL-6, measured with various immunoassays, has shown diagnostic and prognostic value in ILD,” they concluded.