Biomarkers in the Management of Scleroderma: An Update

Abstract

Scleroderma, or systemic sclerosis, is a clinically heterogeneous disease characterized by fibroproliferative vasculopathy, tissue fibrosis affecting the skin and internal organs, and autoimmune activation. Many biomarker candidates have been identified in the past two decades; however, fully validated measures are still lacking with regard to aiding in the early diagnosis and reflecting the disease activity, severity, prognosis, and response to therapy. An ideal biomarker should be highly sensitive and specific, reflecting the current status of disease; should be related to the disease activity and/or severity in accordance with the clinical evolution; should anticipate clinical changes before they occur; and should add independent information about the risk or prognosis that is reproducible and feasible. This review focuses on the most recent and innovative approaches to identify biomarkers, such as extensive gene expression analysis and proteomics, and on markers and surrogate outcome measures closer to clinical practice, and attempts to evaluate them through the OMERACT (Outcome Measures in Rheumatology Clinical Trials) filter.

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

“…The extent of organ involvement and rate of disease progression are the main determinants of morbidity and mortality (25, 46). Pulmonary involvement is the main cause of mortality in SSc, with the most common form of lung involvement being ILD (47).…”

“…Pulmonary involvement is the main cause of mortality in SSc, with the most common form of lung involvement being ILD (47). However, organ involvement and disease phenotype are not easy to predict in patient populations or individuals (25). To address this issue, investigators have focused on biomarkers in this disorder and the criteria that should be used to evaluate them.…”

“…These efforts have led to a number of candidate molecules and scoring systems (reviewed in Refs. 25, 48). They also highlighted the importance of biomarker validity and reproducibility, the ability of the biomarker to discriminate between the situations of interest, and the feasibility of biomarker evaluation (25).…”

“…25, 48). They also highlighted the importance of biomarker validity and reproducibility, the ability of the biomarker to discriminate between the situations of interest, and the feasibility of biomarker evaluation (25). Despite these efforts, validated biomarkers that can serve as surrogate outcome measures in SSc are lacking (25).…”

The enhanced liver fibrosis test: a clinical grade, validated serum test, biomarker of overall fibrosis in systemic sclerosis

“…Therefore, despite intense investigation and the identification of many candidate molecules over the past two decades, fully validated biomarkers that could serve as surrogate outcome measures in clinical trials or to guide clinical management remain an elusive goal 2. Some of the molecules on which biomarker research has focused are collagenous and non-collagenous ECM components, including their metabolites and regulators, which have a clear face validity for the assessment of tissue fibrosis 3…”