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Precision medicine in systemic lupus erythematosus

Nature Reviews Rheumatology volume 19, pages 331–342 (2023)Cite this article

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that has diverse clinical manifestations, ranging from restricted cutaneous involvement to life-threatening systemic organ involvement. The heterogeneity of pathomechanisms that lead to SLE contributes to between-patient variation in clinical phenotype and treatment response. Ongoing efforts to dissect cellular and molecular heterogeneity in SLE could facilitate the future development of stratified treatment recommendations and precision medicine, which is a considerable challenge for SLE. In particular, some genes involved in the clinical heterogeneity of SLE and some phenotype-related loci (STAT4, IRF5, PDGF genes, HAS2, ITGAM and SLC5A11) have an association with clinical features of the disease. An important part is also played by epigenetic varation (in DNA methylation, histone modifications and microRNAs) that influences gene expression and affects cell function without modifying the genome sequence. Immune profiling can help to identify an individual’s specific response to a therapy and can potentially predict outcomes, using techniques such as flow cytometry, mass cytometry, transcriptomics, microarray analysis and single-cell RNA sequencing. Furthermore, the identification of novel serum and urinary biomarkers would enable the stratification of patients according to predictions of long-term outcomes and assessments of potential response to therapy.

Key points

  • Systemic lupus erythematosus (SLE) has heterogeneous clinical presentation, disease course and treatment response.

  • Several new treatments targeting various pathways have gained approval or are under investigation, and a precision-medicine approach to treatment choice is needed.

  • Precision medicine is an emerging approach for disease treatment and prevention that uses individual variability (genomic, transcriptomic, proteomic and metabolomic) to identify patient subgroups that can benefit from specific treatments.

  • Disease-relevant immune subsets identified by immune profiling (helped by recent technological advances) are now shedding light on the cellular and molecular basis of clinical symptoms in individual patients with SLE.

  • Peripheral blood immunophenotyping is identifying molecular networks associated with disease activity, subtype and future relapse, which might provide biomarkers to facilitate the development of stratified treatment recommendations and SLE precision medicine.

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Fig. 1: Genes whose variants are associated with specific manifestations in systemic lupus erythematosus.
Fig. 2: Proposed roadmap towards personalized therapy in systemic lupus erythematosus.

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Author notes

  1. These authors jointly supervised this work: David Isenberg, Francesco Ciccia.

Authors and Affiliations

  1. Rheumatology Unit, Department of Precision Medicine, Università Degli Studi Della Campania “Luigi Vanvitelli”, Naples, Italy

    Serena Fasano, Alessandra Milone & Francesco Ciccia

  2. Multidisciplinary Department of Medical-Surgical and Dental Specialties, Università Degli Studi Della Campania “Luigi Vanvitelli”, Naples, Italy

    Giovanni Francesco Nicoletti

  3. Department of Rheumatology, Division of Medicine, University College London, London, UK

    David A. Isenberg

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  1. Serena Fasano
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  2. Alessandra Milone
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  3. Giovanni Francesco Nicoletti
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  4. David A. Isenberg
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  5. Francesco Ciccia
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Contributions

S.F. and A.M. researched data for the article. S.F., A.M., D.A.I. and F.C. contributed substantially to the discussion of content. S.F. wrote the article. All authors contributed to review and/or editing of the manuscript before submission.

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Correspondence to Serena Fasano or Francesco Ciccia.

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Nature Reviews Rheumatology thanks Antonis Fanouriakis, Mariele Gatto and Keishi Fujio for their contribution to the peer review of this work.

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Fasano, S., Milone, A., Nicoletti, G.F. et al. Precision medicine in systemic lupus erythematosus. Nat Rev Rheumatol 19, 331–342 (2023). https://doi.org/10.1038/s41584-023-00948-y

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