In the majority of patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is the leading cause of death. New research shows that plasma levels of the molecule CXCL4 are higher in patients with interstitial lung disease in systemic sclerosis (SSc-ILD), and that levels of the protein correlate with the response to immunosuppressive treatments and may be a biomarker for ILD’s progression.

Researchers discuss those findings in “Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease,” published in the journal Arthritis Research and Therapy.

CXCL4 is a chemokine, or signaling molecule, that can recruit white blood cells when it is secreted. For ILD patients, higher levels of CXCL4 induce a profibrotic state and bolster the disease.

In Scleroderma Lung Study II (NCT00883129), the researchers investigated how CXCL4 plasma levels change in response to immunosuppressive therapy, and how that correlates with ILD’s progression. They also evaluated baseline levels of CXCL4 in patients compared to healthy controls.

The study involved 142 patients who were randomized to receive either the immunosuppressive drug myophenolate for two years, or the immunosupressive cyclophosphamide for a year, plus a year of placebo. CXCL4 levels were assessed at the start of the study (baseline), then 12 and 24 months afterward. The presence and severity of ILD were assessed using the forced vital capacity (FVC) breathing test.  

At baseline, there were no significant differences in the levels of CXCL4 observed between the patients, but higher CXCL4 levels were observed in them compared to the controls. The results are consistent with studies that have suggested CXCL4 levels correlate with the presence and progression of ILD.

Importantly, the researchers found that CXCL4 levels decreased in response to immunosuppressive therapy. All the patients had decreased levels of the chemokine at 12 and 24 months, compared to their baseline levels. Although CXCL4 levels slightly increased in the placebo phase of the cyclophosphamide treatment, they continued to decline in patients receiving myophenolate.

There were no significant differences in CXCL4 levels between the treatment arms, suggesting that decreases might serve as an overall biomarker of response to immunosuppressive therapy.

After controlling for treatment arm assignment, a time trend, the baseline quantitative extent of ILD/fibrosis, and the baseline FVC, the researches found a significant correlation between CXCL4 levels and the extent of disease. Patients who experienced the greatest decline in CXCL4 levels during the first 12 months of the study also showed significantly improved lung function in months 13 to 24.

“These findings suggest that intermediate-term changes in CXCL4 may have predictive significance for long-term progression of SSc-ILD in patients receiving immunosuppressive therapy,” the team wrote.