Disclosures: The researchers report grant support from the Rheumatology Research Foundation.
July 26, 2021
2 min read

Higher CTRP9 linked to worse pulmonary function in SSc-related interstitial lung disease

Disclosures: The researchers report grant support from the Rheumatology Research Foundation.
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Higher circulating levels of the protein CTRP9 are associated with worse lung function in patients with systemic sclerosis-related interstitial lung disease, according to data published in Arthritis Care & Research.

The researchers additionally concluded that low-circulating CTRP9 was linked to lung disease stability over time, indicating that the protein may be a biomarker for SSc-associated interstitial lung disease.

Higher circulating CTRP9 is associated with worse lung function in patients with SSc-related interstitial lung disease, according to data derived from Yang MM, et al. Arthritis Care Res. 2021;doi:10.1002/acr.24749.

“There is currently a paucity of predictive biomarkers to assess disease progression of SSc-associated ILD (SSc-ILD), representing a significant unmet need in the field,” Monica M. Yang, MD, of the University of California, San Francisco, and colleagues wrote. “Work from our group has demonstrated that altered adipose tissue metabolism is a hallmark of SSc, and a potential pathogenic mechanism underlying fibrosis.”

“Furthermore, we showed that adipokines are associated with specific disease complications and may prove useful as biomarkers,” they added. “To date, the focus on adipokines in SSc has remained primarily on adiponectin, leptin and resistin. A cross-sectional study showed that the novel adipokine, C1q/TNF-Related Protein 9 (CTRP9), was associated with pulmonary complications of SSc.”

To examine the links and potential predictive value of CTRP9 in SSc-related interstitial lung disease, Yang and colleagues conducted a retrospective longitudinal study using the Northwestern Scleroderma Program Patient Registry and Biorepository. Based out of Northwestern University, this resource includes prospectively collected, standardized clinical data for research purposes. The researchers analyzed serum levels of CTRP9 in 110 patients with SSc from the registry at baseline. Demographic, clinical and lung function test data had been collected in 12-month intervals for 48 months.

Among the included patients, a cutoff of greater than 81.1ng/ml — two standard deviations above the mean — was used to define elevated CTRP9 and differentiate between high and low groups. The primary outcome measure was the longitudinal trajectory of forced vital capacity percent predicted (FVC%). The researchers then used a mixed model to compare trajectories of lung function, based on CTRP9 groups, as well as a latent trajectory analysis to accommodate for heterogeneity.

According to the researchers, 34 patients — or 31% of the included total — demonstrated elevated CTRP9 at baseline. In the cross-sectional analysis, elevated CTRP9 was associated with significantly lower FVC% at baseline — 72% ± 17, compared with 80% ± 18 (P = .02) — as well as at 48 months — 68% ± 19, compared with 84% ± 18 (P = .001).

In the mixed model analysis, high CTRP9 was associated with worse lung function, but not with a different trajectory (P = .23). Meanwhile, low CTRP9 was able to, “with reasonable accuracy,” identify patients with stable lung disease, at a sensitivity of 73%, the researchers wrote. In addition, latent trajectory analysis confirmed the link between lower CTRP9 and higher FVC%.

“Variations in circulating CTRP9 in patients with SSc-ILD were associated with lung function,” Yang and colleagues wrote. “Elevated CTRP9 was associated with worse pulmonary function while low CTRP9 was associated with better lung function. Furthermore, we found that CTRP9 levels correlated with circulating monocyte numbers and established a clear trend between baseline CTRP9 and progression of SSc-ILD over time. Taken together, these findings support a novel role for CTRP9 as a prognostic biomarker, and potentially a therapeutic target for SSc-associated lung disease.”