Biomarkers in systemic sclerosis: Their potential to predict clinical courses

Abstract

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 Pselectin were predictive for subsequent physical disability. Further large, multicenter, prospective, longitudinal studies will be needed to identify and validate critical biomarkers of SSc.

Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis

“…The mRNA levels of the TGFβ-regulated genes Thbs1 and Comp have recently been shown to correlate with the changes in the modified Rodnan skin score 41 – 44 as the common clinical readout of skin fibrosis and changes in the mRNA levels of Thbs1 and Comp in fibrotic skin are thus considered as potential biomarkers for SSc. The mRNA levels of Thbs1 and Comp decrease in mice with fibroblast-specific deletion of STAT3 (Fig.…”

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis

“…CXCL4 is a pro-inflammatory chemokine that regulates immune cells, such as T cells, monocytes, dendritic cells, as well as non-immune cells like endothelial cells, and may have an important role in inflammation and wound repair [99,100]. Recently, a proteome-wide analysis has demonstrated that CXCL4 is the predominant protein produced by SSc-derived plasmacytoid dendritic cells and it was identified as a potential biomarker associated with multiple organ involvement in SSc.…”

Systemic sclerosis – diagnostic and therapeutic recommendations of the Polish Dermatological Society. Part 1: diagnosis and monitoring

“…Less common are antibodies directed against fibrillarin (anti-U3-RNP) and against Th/To (the antigen is a ribonucleoprotein complex called the human RNase MRP ribonucleoprotein complex with endonuclease properties). The former are more frequently associated with cardiomyopathy, myopathy and pulmonary arterial hypertension, and the latter are typical of patients with lcSSc (Table 4) [31,32].…”

“…Te pierwsze częś-ciej wiążą się z kardiomiopatią, miopatią i płucnym nadciś nieniem tętniczym, a te drugie są typowe dla chorych na lcSSc (tab. 4) [31,32].…”