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Gene-expression profiling in rheumatic disease: tools and therapeutic potential

Nature Reviews Rheumatology volume 5, pages 257–265 (2009)Cite this article

Abstract

Gene-expression profiling is a powerful tool for the discovery of molecular fingerprints that underlie human disease. Microarray technologies allow the analysis of messenger RNA transcript levels for every gene in the genome. However, gene-expression profiling is best viewed as part of a pipeline that extends from sample collection through clinical application. Key genes and pathways identified by microarray profiling should be validated in independent sample sets and with alternative technologies. Analysis of relevant signaling pathways at the protein level is an important step towards understanding the functional consequences of aberrant gene expression. Peripheral blood is a convenient and rich source of potential biomarkers, but surveying purified cell populations and target tissues can also enhance our understanding of disease states. In rheumatic disease, probing the transcriptome of circulating immune cells has shed light on mechanisms underlying the pathogenesis of complex diseases, such as systemic lupus erythematosus. As these discoveries advance through the pipeline, a variety of clinical applications are on the horizon, including the use of molecular fingerprints to aid in diagnosis and prognosis, improved use of existing therapies, and the development of drugs that target relevant genes and pathways.

Key Points

  • Gene-expression profiling is part of a pipeline that has led to identification of promising biomarkers in rheumatology

  • Sample collection and clinical end points must be considered at an early stage to ensure that high-quality samples and appropriate clinical data are collected

  • Genes and pathways identified by microarray analysis should be validated in independent sample collections and by alternative methods

  • Key genes and pathways identified in gene-expression studies can be examined at the protein level using a variety of multiplexed platforms

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Figure 1: Translation of discovery-based gene-expression microarray data into clinically useful tools.
Figure 2: Principles of RNA-sequencing-based gene-expression analysis.

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  1. Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota, Minneapolis, USA

    Jason W. Bauer, Hatice Bilgic & Emily C. Baechler

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Emily C. Baechler is a co-inventor on the following patent: Behrens, T., Baechler; E. C., Gregersen, P. K. Methods for diagnosing severe systemic lupus erythematosus. US Patent 7,118,865 (2006).

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Bauer, J., Bilgic, H. & Baechler, E. Gene-expression profiling in rheumatic disease: tools and therapeutic potential. Nat Rev Rheumatol 5, 257–265 (2009). https://doi.org/10.1038/nrrheum.2009.50

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