Biomarkers of skin and lung fibrosis in systemic sclerosis

ABSTRACT

Introduction: Excessive fibrosis is the hallmark of systemic sclerosis (SSc) and numerous experts are investing efforts into identifying parameters that could predict disease course and prognosis. Here, we review the available and potential biomarkers of lung and skin fibrosis in SSc.

Areas covered: Specific autoantibodies are important for the determination of clinical subsets of SSc, making them routine in clinical practice. Physical parameters, such as modified Rodnan skin score (mRSS) and pulmonary function tests are standardized in evaluating the skin and lung involvement. High resolution computed tomography is the gold standard for SSc-related interstitial lung disease (ILD) diagnostics, as well as progress evaluation. Nowadays, the main focus is on specific autoantibodies, various genetic pathways, and different cytokines. In addition to the profibrotic role of interleukin 6 and transforming growth factor-β, newer studies stress on glycoprotein Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D) and chemokine (C-C motif) ligand 18 (CCL18) as potential biomarkers of skin and lung fibrosis in SSc.

Expert opinion: Skin and lung biomarkers in SSc frequently mirror the typical signs of fibrosis, overlapping sporadically. There is an urgent need for better diagnostic distinction and evaluation; therefore, further investigations are critical to establish more suitable biomarkers of SSc.

KEYWORDS:

• Autoantibodies
• biomarkers
• cytokines
• fibrosis
• systemic sclerosis

Article Highlights

• SSc is a chronic progressive disease with a wide variety of clinical manifestations; the etiopathogenesis remains unclear, along with unpredictable disease course and outcome.

• Biomarkers in SSc are invaluable for early diagnosis, assessment of disease course and activity monitoring, as well as therapeutic responses.

• For clinicians, mRSS is the gold standard for skin thickness monitoring, while pulmonary function tests and HRCT are essential for evaluation of SSc-related ILD.

• Specific autoantibodies are important serologic markers for determination subclasses and clinical features of SSc.

• Numerous genes and serum proteins are considered to reflect the level of skin and lung changes and ELF score, which combines levels of different serum proteins, was found to be useful as a biomarker of skin and lung fibrosis in SSc.

• Overexpression of type I IFN, TGF-β, PPAR-γ, PI3K-Akt, as well as serum levels of adiponectin, MMP-9, MMP-12, LOX, ADAM12, THBS1, COMP could be used as potential biomarkers of SSc-related skin fibrosis.

• Recent studies stressed importance of genetic pathway dependent on TGF-β and serum levels of IL-6, KL-6, SP-D, and CCL18 as prominent biomarkers for assessing the severity of fibrosis in SSc-related ILD.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.