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Existing and novel biomarkers for precision medicine in systemic sclerosis

Nature Reviews Rheumatology volume 14, pages 421–432 (2018)Cite this article

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Abstract

The discovery and validation of biomarkers resulting from technological advances in the analysis of genomic, transcriptomic, lipidomic and metabolomic pathways involved in the pathogenesis of complex human diseases have led to the development of personalized and rationally designed approaches for the clinical management of such disorders. Although some of these approaches have been applied to systemic sclerosis (SSc), an unmet need remains for validated, non-invasive biomarkers to aid in the diagnosis of SSc, as well as in the assessment of disease progression and response to therapeutic interventions. Advances in global transcriptomic technology over the past 15 years have enabled the assessment of microRNAs that circulate in the blood of patients and the analysis of the macromolecular content of a diverse group of lipid bilayer membrane-enclosed extracellular vesicles, such as exosomes and other microvesicles, which are released by all cells into the extracellular space and circulation. Such advances have provided new opportunities for the discovery of biomarkers in SSc that could potentially be used to improve the design and evaluation of clinical trials and that will undoubtedly enable the development of personalized and individualized medicine for patients with SSc.

Key points

  • An urgent unmet need exists for validated non-invasive biomarkers for the diagnosis, assessment of disease activity and response to therapy of patients with systemic sclerosis (SSc).

  • Biomarkers can be used as easily measurable surrogate markers for clinical end points to aid in the stratification of patients for clinical trials.

  • Current biomarkers for SSc include cutaneous induration and assessment of serum autoantibodies and nailfold capillaroscopic patterns, although only cutaneous induration has been validated for diagnosis, prognosis or response to treatment.

  • Extracellular vesicles (EVs) contain a large number of macromolecules that reflect the physiological or pathological state of the cells of origin, rendering them a novel and valuable source of biomarkers.

  • Transcriptomic and proteomic analyses of EVs isolated from patients with SSc could provide biomarkers for diagnosis, classification and assessment of disease activity, prognosis and therapeutic response.

  • Novel biomarkers will be of value in the provision of precision and personalized medical care to patients with SSc.

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Fig. 1: Timeline of systemic sclerosis biomarker discovery.
Fig. 2: Biogenesis and macromolecular components of exosomes.
Fig. 3: The potential role of extracellular vesicle biomarkers in personalized medicine.

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Acknowledgements

The authors acknowledge the expert assistance of A. Pagano in the preparation of this manuscript. The work of the authors is supported in part by grants R21AR071644 (to S.A.J., P.J.W. and S.P.-V.) and R01AR19616 (to S.A.J.) from the NIH. The work of P.J.W. is supported by a Research Award from the Scleroderma Foundation.

Competing interests

The authors declare no competing interests.

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Authors and Affiliations

  1. Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA

    Peter J. Wermuth, Sonsoles Piera-Velazquez, Joel Rosenbloom & Sergio A. Jimenez

  2. The Joan and Joel Rosenbloom Center for Fibrosis Research, Thomas Jefferson University, Philadelphia, PA, USA

    Peter J. Wermuth, Sonsoles Piera-Velazquez, Joel Rosenbloom & Sergio A. Jimenez

  3. The Scleroderma Center, Thomas Jefferson University, Philadelphia, PA, USA

    Sergio A. Jimenez

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  1. Peter J. Wermuth
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  2. Sonsoles Piera-Velazquez
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S.A.J. and P.J.W. researched data for the article and wrote the article. All authors contributed equally to discussions of the content of the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Sergio A. Jimenez.

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Related links

EVpedia: http://student4.postech.ac.kr/evpedia2_xe/xe/

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Vesiclepedia: http://www.microvesicles.org/

Glossary

Cutaneous induration

Thickening of the dermal and hypodermal layers of the skin as a result of oedema, inflammation or infiltration of immune cells.

Selected reaction monitoring

An emerging targeted mass spectrometry technique for peptide biomarker discovery and validation that is able to quantify the hundreds to several thousands of peptides that are present in complex biofluids in a single experiment.

Aptamers

Short single-stranded modified oligonucleotides that are able to bind to proteins, peptides and small molecules with extremely high specificity.

Biomarker sensitivity

The ability of a biomarker to be measured with adequate precision and with a magnitude of change capable of detection.

Biomarker specificity

The ability of a biomarker to distinguish between patients with different disease subtypes or between patients who do and do not respond to therapy.

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Wermuth, P.J., Piera-Velazquez, S., Rosenbloom, J. et al. Existing and novel biomarkers for precision medicine in systemic sclerosis. Nat Rev Rheumatol 14, 421–432 (2018). https://doi.org/10.1038/s41584-018-0021-9

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