Blood biomarker index helps diagnose SSc-ILD: Study

The index of three biomarkers was also associated with disease severity

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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An index comprising three blood biomarkers was strongly associated with a diagnosis of interstitial lung disease (ILD) in systemic sclerosis (SSc) patients, a study in Australia shows.

The index was also associated with disease severity, independent of lung function.

“Our data supports further investigation of composite biomarker indices as objective, minimally-invasive, point-of-care tests to complement current diagnostic modalities,” the researchers wrote in “A composite serum biomarker index for the diagnosis of systemic sclerosis interstitial lung disease: a multicentre, observational, cohort study,” which was published in Arthritis and Rheumatology.

ILD comprises a group of lung disorders marked by inflammation and fibrosis (scarring). It occurs in up to 80% of patients with SSc, with a higher risk of it in the first three years after the onset of the disease.

A definitive diagnosis of SSc-ILD can only be achieved when irreversible lung injury has occurred. An early and accurate identification is important to identify effective therapies that can slow its progression, however.

Blood biomarkers have been looked at as a diagnostic tool for SSc-ILD since they are minimally invasive. Several have previously provided indications on the mechanisms that lead to pulmonary fibrosis.

Researchers in Australia explored whether a combination of blood biomarkers could contribute to diagnosing ILD in SSc patients. They analyzed 28 blood biomarkers in people with SSc, a control group with idiopathic pulmonary fibrosis (IPF), and a group of healthy controls.

A total of 610 patients met the inclusion criteria, including 259 (40.5%) with SSc-ILD, 179 (27.9%) SSc-controls without ILD, and 172 (26.9%) with IPF. Thirty (4.7%) healthy people also participated as controls.

The overall mean age was 60 and most participants were women (67.3%). The median follow-up time was between 60.7-69.7 months (about five to six years).

More than half the participants (55.9%) had never smoked and had mild to moderate lung function impairment. The deterioration of lung function was less severe in those with SSc-ILD compared to those with IPF, but more severe than SSc patients without ILD.

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Benefit of composite approach in diagnosing ILD

SSc-ILD patients had a significantly higher prevalence of anti-Scl70 autoantibodies than SSc-controls (38.5% vs. 9.3%), a lower prevalence of anti-centromere autoantibodies (18.8% vs. 49.4%), and were more likely to have received immunomodulator therapy (63.7% vs. 46.9%).

The researchers identified three independent blood biomarkers associated with ILD — surfactant protein D (SP-D), intercellular adhesion molecule-1 (ICAM-1), and cancer antigen 15-3 (CA15-3).

SP-D plays an important role in the immune system. ICAM-1 mediates the migration of white blood cells into the area between blood vessels and the lung air sacs. CA15-3, most commonly known as a tumor marker, is found on the surface of epithelial cells in various organs.

A composite index of these biomarkers was able to discriminate SSc-ILD patients from those with SSc, but not ILD, independent of age, sex, smoking history, and forced vital capacity (FVC) — the amount of air that can be forcibly exhaled from the lungs after a deep breath. The index was validated as a marker of ILD diagnosis and disease severity.

Specifically, if the index score was 2 or more, it was strongly associated with ILD and was able to discriminate ILD patients (SSc-ILD and IPF) from those without ILD. Similar results were found after adjusting for SSc disease duration.

These biomarkers levels were found to be elevated in response to processes associated with fibrosis in both SSc-ILD and IPF patients, the researchers noted.

“We demonstrated that combining these biomarkers into a simple composite index strengthened their performance characteristics in a robust, easy to calculate tool,” they wrote.

Also, in SSc patients, a biomarker index of 2 or more was associated with a more severe impairment in measures of lung function and disease.

We demonstrated that combining these biomarkers into a simple composite index strengthened their performance characteristics in a robust, easy to calculate tool.

The ability of the index to distinguish lung function was not affected by immunomodulatory therapy.

“We believe this composite approach is more reflective of the complex clinical and molecular heterogeneity of SSc-ILD, and less liable to environmental or genetic confounders compared with individual  markers,” the researchers wrote.

The biomarker index was also not associated with health-related quality of life.

According to the scientists, blood biomarkers are unlikely to replace high-resolution CT scans or lung function for diagnosis or severity assessment of SSc-ILD, but may help when standard tests are indeterminate or confounding factors exist.

“The utility of biomarkers to guide the selection of SSc-ILD patients for immunomodulatory therapy, antifibrotics, or both, remains an urgent unmet need,” the researchers wrote, adding the “analysis of our biomarker panel to predict progressive disease is ongoing.”