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CXC-Chemokine Ligand 10 in Idiopathic Pulmonary Arterial Hypertension: Marker of Improved Survival

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Abstract

CXC-chemokine ligand 10 (CXCL10) inhibits angiogenesis and attracts activated T lymphocytes. Abnormal angiogenesis and lymphocytic infiltration participate in the pathobiology of pulmonary arterial hypertension (PAH). We hypothesized that serum CXCL10 is elevated in idiopathic PAH and that it is associated with clinical outcomes. This was a cohort study that included 40 idiopathic PAH patients (age = 44 ± 14 years, 37 females) and 22 healthy controls (age = 35 ± 6 years, 18 females). It took place at the Pulmonary Vascular Program at the Cleveland Clinic. Serum CXCL10 levels were measured by an enzyme-linked immunosorbent assay. A cutoff value of CXCL10 for best distinguishing alive and dead patients was obtained from a receiver operating characteristic curve (ROC). Survival and time to clinical worsening curves according to the appropriate CXCL10 level were derived by the Kaplan–Meier method and compared by means of the log-rank test. The prognostic value of CXCL10 and of other variables of interest was tested by Cox proportional hazards regression analysis. Serum CXCL10 levels were elevated in PAH subjects compared to controls [CXCL10 pg/ml (mean ± SEM) for PAH: 306 ± 73, and for controls: 92 ± 10; p < 0.0001]. CXCL10 levels higher than 111 pg/ml discriminated survivors from nonsurvivors with a sensitivity of 81% and a specificity of 75% (area under the ROC curve = 0.74). After a mean follow-up of 23.5 ± 13.5 months since the day of venous sampling, higher CXCL10 levels were associated with improved survival (hazard ratio for mortality = 0.10, 95% confidence interval = 0.01–0.97; p = 0.01). Serum CXCL10 is elevated in PAH and this is associated with improved survival.

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Acknowledgment

This work was supported by the National Institutes of Health (grant NIH HL68863).

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Authors and Affiliations

  1. Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue A90, Cleveland, OH, 44195, USA

    Gustavo A. Heresi, Jennie Newman & Raed A. Dweik

  2. Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Metin Aytekin

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  1. Gustavo A. Heresi
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Heresi, G.A., Aytekin, M., Newman, J. et al. CXC-Chemokine Ligand 10 in Idiopathic Pulmonary Arterial Hypertension: Marker of Improved Survival. Lung 188, 191–197 (2010). https://doi.org/10.1007/s00408-010-9232-9

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