A 3D illustration of cytokines.
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A recent prospective, observational cohort study of potential clinical biomarkers for progression to interstitial lung disease (ILD) in patients with early systemic sclerosis (SSc) found that higher levels of CCL2 circulating in their plasma predicted both faster ILD progression and poorer survival rates than in those with lower levels.1
CCL2, also known as monocyte chemoattractant protein-1, is a small cytokine belonging to the CC chemokine family. Cytokines are substances, such as interferon, interleukin and growth factors, secreted by cells in the immune system that have immunologic effects on other cells. Cytokines can be either pro-inflammatory or anti-inflammatory, and can be further subdivided into Th1-type and Th2-type cytokines.
The Study
The new study’s results combine two independent cohorts of patients with early SSc in Texas and Canada to examine the predictive significance of cytokines and chemokines for long-term progression of SSc-related ILD, says lead author Minghua Wu, MD, of the University of Texas Health Sciences Center in Houston. She and colleagues in Texas measured plasma levels obtained at baseline for 11 key cytokines using a highly sensitive multiplex sandwich immunoassay.
The Genetics vs. Environment in Scleroderma Outcome Study (GENISOS) in Texas tested a total of 266 patients with early SSc, along with 97 matched healthy controls. The companion replication cohort study by the Canadian Scleroderma Research Group looked for several of the same cytokines, including CCL2, in serum samples of 171 patients.
Researchers adjusted for age, sex and ethnicity, and the results remained independent of other biomarkers. The most significant finding indicated higher levels of CCL2 predicted faster decline in forced vital capacity (FVC), a measure of lung function that served as a surrogate for the severity of SSc-related ILD. Researchers tested FVC at patients’ initial visit and annually thereafter, with a mean follow-up from 4.36–5.72 years.
Among the 11 cytokines under examination by the Texas group, the data showed IL-10 was a significant predictor of ILD progression as well, but in the opposite direction: Higher IL-10 levels in the plasma meant slower progression. The Canadian data did not repeat this IL-10 finding.
Higher levels of CCL2 … predicted faster decline in forced vital capacity (FVC), a measure of lung function.
A New Therapeutic Target?
SSc, an autoimmune fibrotic disease that presents a distinct cytokine profile, is associated with high mortality, with few treatment options and no single Food and Drug Administration-approved medication for SSc-related ILD, says Dr. Wu’s UT colleague, Shervin Assassi, MD. “ILD, along with other pulmonary involvement, is the primary cause of mortality in this population,” he says. “The course of ILD is highly variable. The few existing clinical predictors of progression [we have] have not [proved] sufficient.