CTRP9 Protein Levels May Be Biomarker of Lung Disease Severity

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by Forest Ray PhD |

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This illustration shows a patient's damaged lungs.

High levels of a protein known as CTRP9 appear to indicate worsening lung function in patients with systemic scleroderma (SSc), according to a recent study. The discovery suggests that CTRP9 may be a useful biomarker for the loss of lung function in SSc.

Such biomarkers are sorely needed, researchers said, given that diseases that cause scarring of lung tissue — known as interstitial lung diseases or ILD — are linked to poor outcomes for people with SSc.

“While interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc), there remains a paucity of predictive markers to assess disease progression,” the scientists wrote. “These findings suggest that CTRP9 may be a potential biomarker in SSc-associated ILD.”

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Their study, “Circulating CTRP9 is Associated with Severity of Systemic Sclerosis-associated Interstitial Lung Disease,” was published in the journal Arthritis Care & Research.

Past research had demonstrated that fat metabolism is disrupted over the course of SSc. Moreover, the cell-signaling molecule CTRP9, made within fat cells, is associated with pulmonary complications in that disorder.

Now, researchers from across the United States teamed up to investigate this relationship further, looking at how changes in CTRP9 levels correlated with changes in pulmonary function in SSc patients.

Overall, they found high levels of CTRP9 associated with declining pulmonary function. Meanwhile, low CTRP9 protein levels corresponded to a more stable disease course over time.

These results make the protein a potential disease biomarker, the team said.

To arrive at this conclusion, they reviewed the records of 110 individuals included in the Northwestern Scleroderma Patient Registry and Biorepository, led by Northwestern University, in Illinois. Among the cases reviewed, 61 involved patients with limited cutaneous SSc, and 49 pertained to those with diffuse cutaneous SSc. Most patients (70) had four years’ worth (48 months) of pulmonary function tests, taken at 12-month intervals. Mean disease duration was 9.7 years.

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Patients with more CTRP9 in their bloodstream (over 81.1 nanograms/ml) generally had significantly worse lung function at the study’s start, and at 48 months, as measured by forced vital capacity (FVC) and DLCO — standard measures of how much air a person can exhale after a forced breath, and of predicting the lungs’ capacity to transfer oxygen to blood cells.

Additionally, high CTRP9 levels were associated with greater numbers of monocytes, cells known to contribute to lung fibrosis, or scarring. Low CTRP9 was associated with a decrease in monocytes, even after accounting for disease duration and treatment status.

Notably, the data showed that patients with stable disease — those whose FVC changed by less than 3% over the study period — tended to have low levels of CTRP9.

Although CTRP9 levels did not appear to predict SSc progression so much as changes in lung function, the researchers suggested that the possibility cannot yet be ruled out.

“Development and progression of ILD in SSc is often early with a steep progression early on in disease,” they wrote, adding that because the patients in this study had an average disease duration of about nine years, they may have already reached the “plateau” phase of their lung disease.

Other factors, such as the study’s sample size and variability in regard to disease duration and treatment status cannot be excluded, the investigators added. Future studies, they mentioned, should examine CTRP9’s prognostic value in greater detail.

The group, involving researchers from the University of California San Francisco, the Yale School of Medicine, in Connecticut, the University of Michigan, and the University of Rochester Medical Center, in New York, in addition to Northwestern, now plans to study CTRP9 gene variants, to determine how the gene’s expression, or activity, might be altered in SSc with interstitial lung disease.

Their current findings, they concluded, “support a novel role for CTRP9 as a prognostic biomarker, and potentially a therapeutic target for SSc-associated lung disease.”