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Biomarkers of Lung Involvement in Systemic Sclerosis (SSc) FREE TO VIEW

Stephan van Eeden, MD; Siamak Salami, MD; Terence Yung, BSc; Murray Baron, MD
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iCapture Centre, UBC, Vancouver, BC, Canada

Chest. 2010;138(4_MeetingAbstracts):793A. doi:10.1378/chest.9975
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PURPOSE: Scleroderma vascular disease is thought to play a fundamental role in the pathogenesis of tissues remodeling and fibrosis. The mechanisms of this widespread vascular disease are still unknown, but endothelial cell injury with disregulated repair and remodeling is a key early event. Circulating “biomarkers” of vascular damage may reflect disease activity and outcome and in this study we measured circulating angiogenic and angiostatic factors to determine the relationship between these biomarkers and lung disease in scleroderma.

METHODS: Serum samples of SSc patients were selected from the Canadian Scleroderma Research Group (CSRG) biobank. The Luminex xMAP multiplex (R&D and BioLegend) were used to measure circulating levels of angiogenic (VEGF and it’ s receptors R1 and R2, PDGF-BB, MCP-1) and angiostatic (endostatin, thrombospondin-2, Granzyme B) factors and relate to clinical characteristics (diffuse vs. limited) subtypes, disease activity scores, lung functions and pulmonary arterial pressures (PAP measure by echocardiography). Lung damage scores were tested as a surrogate marker for lung involvement in SSc.

RESULTS: Subjects with PAP >30mmHg, DLCO<80 and FVC<80% of predicted were studied (n=120). Corrected for smoking, age and sex: angiostatic factors TBS-2 (28.9±2.7 vs 40.4±3.6 ×103 pg/ml, p<0.03) and endostatin (109.1±8.8 vs 130.1±6 ×103 pg/ml, p<0.05) was higher in patients with PAH (PAP>35mmHg) and TBS-2 correlated with the PAP levels, r2=0.21, p<0.03). PDGF correlated with overall disease severity (sum of 9 scores) (r2=0.37, p<0.003). These relationships were stronger in limited disease compared to diffuse disease. High Lung Damage Scores were associated with lower levels of angiostatic factors (TBS-2, endostatin and GZB [p<0.05]).

CONCLUSION: We conclude that depressed levels of circulating angiostatic factors are associated with lung involvement in SSc except if there is significant PAH and these associations are stronger in limited disease.

CLINICAL IMPLICATIONS: We speculate that angiostatic factor maybe good biomarkers to follow progression of lung disease in SSc.

DISCLOSURE: Stephan van Eeden, No Financial Disclosure Information; No Product/Research Disclosure Information

08:00 AM - 09:15 AM




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