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Immune-cell profiling to guide stratification and treatment of patients with rheumatic diseases

Nature Reviews Rheumatology volume 21, pages 657–670 (2025)Cite this article

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Abstract

Methods for high-dimensional immune-cell profiling have advanced dramatically in the past decade. Studies of tissue and blood samples from patients with rheumatic diseases have revealed stereotyped features of immune dysregulation in individual diseases and in subsets of patients who share diagnosis of a heterogeneous disease. Translating immunological patterns into clinically implementable, actionable biomarkers has the potential to improve detection and quantification of pathological immune activity and selection of appropriate treatments for autoimmune rheumatic diseases. For example, cytometric features can be used to distinguish the various forms of inflammatory arthritis, stratify subsets of patients with rheumatoid arthritis or subsets of patients with systemic lupus erythematosus and predict treatment responses. Cellular immune profiling also enables the identification of specific features of immune dysregulation in individuals with rare, undiagnosed, inflammatory diseases. Several paths might lead to translation of discoveries from broad immune profiling into clinical tests to interrogate immune activation in people with rheumatic diseases.

Key points

  • Profiling of immune cells in blood and tissue from patients with rheumatic diseases has helped to define populations of activated immune cells that are characteristically expanded in specific diseases, highlighting both unique and shared features across diseases.

  • Immune profiling of patients with SLE has identified specific axes of immune dysregulation, including activation of type I IFN pathways, proliferation of lymphocytes, expression of cytotoxic molecules on T cells and upregulation of myeloid cell- and neutrophil-associated signatures; these features vary across patients and help to delineate subgroups of patients that differ in immune activity.

  • Longitudinal evaluation of cellular profiles of patients receiving treatments targeting rheumatic disease helps to associate immunological features with treatment effects and predict response to treatment.

  • Incorporation of immune profiling into clinical evaluation of patients with rheumatic diseases might enable improved patient stratification, assessment of disease activity and prediction of treatment response.

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Fig. 1: Focused immune assessments to identify immune dysregulation in patients with suspected systemic lupus erythematosus.
Fig. 2: Broad immune profiling to identify immune abnormalities in rheumatic diseases.

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Acknowledgements

D.A.R. has been supported in part by the Burroughs Wellcome Fund Career Award in Medical Sciences and the Doris Duke Clinical Scientist Development Award. I thank Kevin Wei, Craig Platt, Kathryne Marks and Daimon Simmons for helpful discussions.

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  1. Division of Rheumatology, Inflammation, Immunity, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Deepak A. Rao

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D.A.R. reports grant support from Janssen, Merck and Bristol Myers Squibb outside of the current report, and reports personal fees from AstraZeneca, Merck, AbbVie, Biogen, Simcere, Epana, HiFiBio and Bristol Myers Squibb. He is co-inventor on a patent using TPH cells as a biomarker of autoimmune diseases.

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Rao, D.A. Immune-cell profiling to guide stratification and treatment of patients with rheumatic diseases. Nat Rev Rheumatol 21, 657–670 (2025). https://doi.org/10.1038/s41584-025-01291-0

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