Blood Levels of KL-6 Protein May Detect Interstitial Lung Disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Levels of a protein called KL-6 are elevated in ANCA-associated vasculitis (AAV) patients who have interstitial lung diseases, indicating that KL-6 blood levels could be useful for detecting lung disease in these people, a study suggests.

The study, “KL-6 in ANCA-Associated Vasculitis Patients with and without ILD: A Machine Learning Approach,” was published in Biology.

Interstitial lung diseases, or ILDs, are a group of inflammatory disorders characterized by scarring in the lungs. Normally, the lungs need to be stretchy and flexible to inflate and deflate while breathing, but scar tissue makes the lungs stiffer and hinders their ability to absorb oxygen.

ILDs can occur with AAV, particularly in a subtype of AAV called microscopic polyangiitis or MPA. However, such lung diseases in AAV patients can go undiagnosed, as diagnosing them often requires an invasive lung biopsy.

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KL-6 (Krebs von den Lungen-6) is a mucin — a mucus protein — that recent research suggests may be a diagnostic marker of ILDs in the general population. Whether KL-6 could be useful for identifying ILDs among AAV patients has not been thoroughly studied.

Scientists in Italy and Spain analyzed KL-6 levels in the blood of 12 people with AAV. Their median age was 59.5, and their median time spent living with AAV was just over two years (26 months). Most of  these patients, eight of the 12, were female.

Six had MPA, and the other six had granulomatosis with poplyangiitis (GPA), another form of AAV. Four had been diagnosed with ILD. Average blood levels of KL-6 were significantly higher in patients with ILD compared to those without it (972.8 vs 305.4 units per milliliter, or U/mL).

As expected, a greater percentage of MPA patients had an ILD, compared with the GPA population (20% vs. 10%).

KL-6 levels correlated significantly with Birmingham Vasculitis Activity Score (BVAS), suggesting that levels of this protein were higher in patients with more severe AAV. However, previous treatment did not impact KL-6 levels in people with both AAV and ILD.

Further analyses indicated that a cut-off of 368 U/mL could identify ILD patients with a sensitivity (true-positive rate) of 100%, and a sensitivity (true-negative rate) of 87.5%. The team showed that further accuracy could be obtained using machine learning and a cutoff value of 513 U/mL.

“The present study suggests a KL-6 cut-off value below 513 U/mL of serum, which may be particularly useful in patients in whom clinical (such as GPA) and serological features are not strongly associated with the onset of ILD,” the researchers wrote.

Based on these findings, they concluded that measuring KL-6 blood levels could be useful for detecting or monitoring ILD in AAV patients.

They noted a need for further studies to validate these results, and added that “further research lines should be addressed in order to assess whether KL-6 changes may be related to disease clinical course or response to treatment.”