Biomarkers in systemic sclerosis: Their potential to predict clinical courses

The concept of a biomarker was defined as "a characteristic marker that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention" by the National Institutes of Health Biomarkers Definitions Working group in 2001. Clinical features, disease progress, therapeutic response and prognosis are heterogeneous among patients with systemic sclerosis (SSc). Therefore, biomarkers that can predict these matters are required for the progress of clinical practice. At present, SSc-specific autoantibodies are the most useful biomarkers for diagnosis and predicting clinical features. Otherwise, biomarkers specific only for SSc have not been identified yet. The glycoprotein krebs von den Lungen-6, surfactant protein-D and CCL18 are promising serum biomarkers of SSc-related interstitial lung diseases. Serum/plasma levels of brain natriuretic peptide and serum N-terminal pro-brain natriuretic peptide have been used as biomarkers for SSc-related pulmonary arterial hypertension. Other potential serum/plasma biomarkers for fibrosis and vascular involvement of SSc are connective tissue growth factor, interleukin-6, CCL2, CXCL4, intercellular adhesion molecule (ICAM)-1, P-selectin, vascular endothelial growth factor, von Willebrand factor, endostatin, endoglin and endothelin-1. In our multicenter prospective studies of Japanese early SSc, serum ICAM-1 levels were predictive for subsequent respiratory dysfunction and serum levels of CXCL8 and P-selectin were predictive for subsequent physical disability. Further large, multicenter, prospective, longitudinal studies will be needed to identify and validate critical biomarkers of SSc.