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  • Review Article
  • Published:

Immune cell profiling to guide therapeutic decisions in rheumatic diseases

Key Points

  • Immune cell profiling to provide prognostic information and predict treatment responses is not yet part of clinical rheumatology practice

  • Novel technologies, including mass cytometry, RNA-seq and multiplexed functional assays, promise insight into the pathogenesis of rheumatic diseases with unprecedented detail and might lead to the discovery of new biomarkers

  • Computational and statistical approaches for managing and analysing big data need to be refined to achieve the full potential of these assays

  • Assay standardization and the definition of normal values are prerequisites for the introduction of high-dimensional cytometry, genome-wide gene expression analysis and multiplexed functional assays into clinical practice

  • Immune cell profiling has the potential to improve outcomes in rheumatic diseases by providing mechanistic insight into the disease process in individual patients and guiding treatment decisions

Abstract

Biomarkers are needed to guide treatment decisions for patients with rheumatic diseases. Although the phenotypic and functional analysis of immune cells is an appealing strategy for understanding immune-mediated disease processes, immune cell profiling currently has no role in clinical rheumatology. New technologies, including mass cytometry, gene expression profiling by RNA sequencing (RNA-seq) and multiplexed functional assays, enable the analysis of immune cell function with unprecedented detail and promise not only a deeper understanding of pathogenesis, but also the discovery of novel biomarkers. The large and complex data sets generated by these technologies—big data—require specialized approaches for analysis and visualization of results. Standardization of assays and definition of the range of normal values are additional challenges when translating these novel approaches into clinical practice. In this Review, we discuss technological advances in the high-dimensional analysis of immune cells and consider how these developments might support the discovery of predictive biomarkers to benefit the practice of rheumatology and improve patient care.

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Figure 1: Cellular immunophenotyping by multiparameter single-cell analysis.
Figure 2: Timeline of technical advances.
Figure 3: Methods for genome-wide and multiparameter gene expression analysis.
Figure 4: In vitro assays of cell function.
Figure 5: Analysing and displaying large complex data sets.

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Acknowledgements

J.E. is supported by an NIH grant R03AR066357-01A1 and a Disease Targeted Research Pilot Grant from the Rheumatology Research Foundation. D.A.R. is supported by an NIH training grant T32 5T32AR007530. M.B.B. is supported by NIH grant 1UH2AR067694-01. S.R. is supported by NIH grants 1U01HG0070033, 1R01AR063759-01A1, 5U01GM092691-04, 1UH2AR067677-01, and 1R01AR065183-01.

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J.E., D.A.R. and N.C.T. researched data for the article. S.R., J.E., D.A.R. and N.C.T. substantially contributed to discussion of content and writing the manuscript. All authors contributed to review/editing of the manuscript before submission.

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Correspondence to Joerg Ermann.

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Ermann, J., Rao, D., Teslovich, N. et al. Immune cell profiling to guide therapeutic decisions in rheumatic diseases. Nat Rev Rheumatol 11, 541–551 (2015). https://doi.org/10.1038/nrrheum.2015.71

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