Immune monitoring using mass cytometry and related high-dimensional imaging approaches

The cellular complexity and functional diversity of the human immune system necessitate the use of high-dimensional single-cell tools to uncover its role in multifaceted diseases such as rheumatic diseases, as well as other autoimmune and inflammatory disorders. Proteomic technologies that use elemental (heavy metal) reporter ions, such as mass cytometry (also known as CyTOF) and analogous high-dimensional imaging approaches (including multiplexed ion beam imaging (MIBI) and imaging mass cytometry (IMC)), have been developed from their low-dimensional counterparts, flow cytometry and immunohistochemistry, to meet this need. A growing number of studies have been published that use these technologies to identify functional biomarkers and therapeutic targets in rheumatic diseases, but the full potential of their application to rheumatic disease research has yet to be fulfilled. This Review introduces the underlying technologies for high-dimensional immune monitoring and discusses aspects necessary for their successful implementation, including study design principles, analytical tools and future developments for the field of rheumatology. Single-cell proteomic techniques that use elemental (heavy metal) reporter ions increase the number of parameters that can be studied at once in whole tissues. This Review discusses the practical aspects of using such technologies in rheumatic disease research. Key points Immune monitoring of human cells using systems immunology approaches has the potential to produce new insights into pathological processes and therapeutic opportunities for rheumatic disease research. Proteomic approaches that use elemental (heavy metal) reporter ions, such as mass cytometry and high-dimensional imaging techniques, might be of value for the study of a wide variety of clinical samples. Mass cytometry enables in-depth analysis of the phenotype and functional state of immune cells at the single-cell level. High-dimensional imaging techniques use concepts analogous to mass cytometry to image cells in their histological context, providing spatial and cell–cell interaction information. A combination of these technologies with data-driven analytical approaches can give predictive insights into disease mechanisms for rheumatic diseases.