Levels of the cytokine CXCl4 in the bloodstream drop sharply in response to immunosuppressive therapy, and are associated with improved lung function in systemic sclerosis (SSc) patients with interstitial lung disease (ILD), a study shows.
The research, “Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease,” was published in the journal Arthritis Research & Therapy.
CXCL4 has been identified as a blood biomarker for ILD in patients with SSc. Previous studies have found higher CXCL4 levels in SSc patients with ILD than in those without ILD. Furthermore, SSc patients with high levels of CXCL4 when the studies began showed accelerated progression of ILD.
Researchers investigated the potential association between CXCL4 levels and the extent of ILD in SSc patients in a randomized controlled trial. They also investigated how alterations in CXCL4 levels might predict improved lung function in patients receiving mycophenolate or cyclophosphamide. The two are immunosuppressant therapies, meaning they suppress, or reduce, the strength of the body’s immune system.
The research team recruited 142 SSc-ILD patients from the Scleroderma Lung Study (SLS) II (NCT00883129). The participants were randomly assigned to receive mycophenolate for two years or oral cyclophosphamide for one year, followed by one year of placebo.
Researchers measured CXCL4 when the study began, at 12 months, and at 24 months in 136 SLS II participants. In the 67 healthy controls, CXCL4 levels were measured at a single time point.
The team observed that CXCL4 levels at baseline, or when the study began, were significantly higher in SSc-ILD patients than in healthy controls. However, no correlation was found between CXCL4 levels and the extent of ILD at baseline. ILD extent was determined by a measurement of lung function known as forced vital capacity (FVC), the lung’s diffusing capacity of carbon monoxide, and the extent of ILD in X-rays.
Immunosuppressive therapy, either with mycophenolate or cyclophosphamide, was found to be associated with a significant reduction in CXCL4 levels. Additionally, patients with a more pronounced decline in CXCL4 levels from baseline to 12 months showed improvements in SSc-ILD at 24 months, as determined by improvements in FVC.
“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 concluded. “Although the exact role of CXCL4 in the pathobiology of SSc-ILD is uncertain, these findings support the potential predictive capability of this chemokine for determining response to immunosuppressive therapy.”