Cytokine profiles distinguish risk for pulmonary arterial hypertension in systemic sclerosis
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Cytokine profiles can distinguish patients with systemic sclerosis who are at high risk for, or have, pulmonary arterial hypertension from those with low risk and healthy controls, according to data published in Arthritis Research & Therapy.
“Pulmonary arterial hypertension (PAH) is still a major cause of death in patients with systemic sclerosis despite the availability of multiple approved therapies,” Lorinda Chung, MD, MS, of the Stanford University School of Medicine and the Palo Alto VA Health Care System, in California, told Healio. “However, many studies have shown that screening for PAH and instituting early treatment improves survival and other outcomes. Developing a simple blood test to identify patients who are at high risk for developing PAH would be extremely useful in the early detection and treatment of these patients.”
To identify serum cytokine signatures that distinguish patients with SSc at high risk for PAH, Kolstad and colleagues analyzed data and serum samples from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) study. According to the researchers, PHAROS is a U.S.-based, multicenter registry of patients with SSc who are at high risk for, or have, PAH based on right heart catheterization, within 6 months of enrollment. Meanwhile, patients with SSc at low risk for PAH and health controls, with no known autoimmune disease, were enrolled at Stanford University.
In all, the researchers analyzed serum from 71 patients at high risk for PAH, 81 with incident PAH, 10 low-risk patients and 20 healthy controls. Kolstad and colleagues used custom 14- and 65-plex arrays for their cytokine analysis, with cytokine expression compared between patient groups based on principal component analysis and Tukey’s test result. Significance was defined as a multiple-hypotheses corrected P value of less than 0.05.
According to the researchers, the exploratory analysis, with principal components, demonstrated unique clustering for each patient group. In addition, there was a significant variance in cytokine expression in at least one group comparison for each cytokine. In all, the researchers reported “very little” difference in cytokine expression between the high-risk and incident PAH patient groups, they wrote. However, these two groups demonstrated substantially different cytokine profiles versus patients at low risk and healthy controls.
“Using serum samples from a multi-center U.S. registry of SSc patients called PHAROS, we found that serum cytokine signatures were very similar in SSc patients who are at high risk for PAH — based on clinical parameters such as echo and pulmonary function tests — to those who have right heart catheterization-proven PAH,” Chung said. “In contrast, cytokine signatures were markedly different from SSc patients at low risk for PAH and healthy controls. Our study is the first step to developing a blood test to identify SSc patients at high risk for developing PAH, but validation studies are necessary.”
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