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. We previously demonstrated that adipose tissue metabolism and adipokine homeostasis is dysregulated in SSc. We sought to determine the association and predictive ability of the novel adipokine C1q/TNF-Related Protein 9 (CTRP9) for SSc-ILD.
We performed a retrospective longitudinal study utilizing the Northwestern Scleroderma Program Patient Registry and Biorepository. Serum levels of CTRP9 were measured in 110 SSc patients at baseline, and demographic, clinical and pulmonary function test data were collected in 12-month intervals to 48 months. Longitudinal trajectory of forced vital capacity percent predicted (FVC%) was used as a primary outcome measure. We utilized a mixed model to compare trajectories of lung function by CTRP9 groups and performed latent trajectory analysis to accommodate for heterogeneity.
In cross-sectional analysis, elevated circulating CTRP9 was associated with significantly lower FVC% at baseline (72%±17 vs. 80%±18, p=0.02) and 48 months (68±19 vs. 84±18, p=0.001). In mixed model analysis, high CTRP9 was associated with worse lung function, but not with a different trajectory (p=0.23). In contrast, low CTRP9 identified patients with stability of lung disease with reasonable accuracy (sensitivity=73%). Latent trajectory analysis confirmed the association of lower CTRP9 with higher FVC%.
Higher circulating CTRP9 associated with worse pulmonary function while low CTRP9 identified patients with lung disease stability over time. These findings suggest that CTRP9 may be a potential biomarker in SSc-associated ILD.