Cytokine Profiles Identify Risk of PAH in SSc

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Levels of signaling molecules called cytokines can be used to identify people with systemic scleroderma (SSc) who are at highest risk of developing abnormally high blood pressure in their lungs, a new study reports.

The study, “Cytokine signatures differentiate systemic sclerosis patients at high versus low risk for pulmonary arterial hypertension,” was published in the journal Arthritis Research & Therapy.

About one of every 10 people with SSc will develop pulmonary arterial hypertension (PAH) — a condition defined by abnormally high pressure in the blood vessels in the lungs, which strains the heart and leads to symptoms like shortness of breath and fatigue.

An early diagnosis and prompt treatment can help improve outcomes related to PAH, so routine screening is generally advised. However, the gold standard to check for PAH, called right heart catheterization (RHC), is an invasive procedure that involves inserting a very thin tube into the heart and the lungs’  blood vessels. There is an ongoing search to find less-invasive tests that can detect PAH, and identify the patients at highest risk of PAH.

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Here, a team led by scientists at Stanford University in California led a series of tests to look for cytokine signatures associated with PAH in SSc. Cytokines are a broad class of small proteins that cells use to communicate with each other; they help to govern processes like inflammation.

For the analyses, the researchers collected blood samples from 81 SSc patients who had been diagnosed with PAH via RHC, as well as 71 who were considered high risk for PAH based on measures of lung function and/or blood pressure inside the artery that supplies blood to the lungs. The analysis also included 10 people with SSc deemed to be at low risk of PAH, and 20 healthy participants serving as controls. In all groups, most participants were women.

The blood samples were analyzed to detect levels of various cytokines, and then the researchers used statistical tests to look for differences among the groups.

Results showed that SSc patients who had PAH, or were at high risk for it, had higher-than-normal levels of pro-inflammatory cytokines, such as IL-6 and TNF-alpha. By contrast, SSc patients who were low-risk for PAH had similar levels of TNF-alpha as the healthy controls, though there was no significant differences between low-risk SSc patients and high-risk SSc patients, or those with PAH.

Taken as a whole, the researchers concluded that assessing cytokine levels could consistently distinguish SSc patients who either had PAH or were at high risk of PAH, from those at low risk. However, there were no clear differences in cytokine profiles between those deemed high-risk, and those who actually had diagnosed PAH.

“Our data suggest that cytokine profiles can differentiate SSc patients who are at high-risk for or have PAH from SSc patients at low risk for PAH and healthy controls,” the team wrote. “However, high-risk and PAH patients had very similar cytokine profiles, suggesting that these patients are on a disease continuum.”

“We anticipate these data could be used to risk stratify [classify] SSc patients and guide therapy,” the researchers added. They also suggested that some of the cytokines that are elevated in SSc patients at higher risk for PAH might be explored as possible therapeutic targets in future research.

The team noted that more studies are needed to validate these results, particularly stressing a need for further analyses that include more low-risk patients.