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Insights into the pathogenesis of childhood-onset SLE in the past decade

Nature Reviews Rheumatology volume 22, pages 26–41 (2026)Cite this article

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Abstract

Childhood-onset systemic lupus erythematosus (SLE) is associated with more active disease trajectories, increased cardiovascular risk, earlier development of organ damage (which commonly affects the kidney, central nervous and musculoskeletal systems) and increased use of glucocorticoids and immunosuppressive treatments than adult-onset SLE. However, the understanding of immunopathogenic mechanisms in childhood-onset SLE is far less established than in adult-onset disease. Technological advances over the past decade have accelerated progress in understanding the immune, genetic, epigenetic, metabolic and proteomic profiles of childhood-onset SLE, and have also established the mechanistic roles of immune dysregulation, interferon signalling, biological sex, gender and ethnicity in shaping disease heterogeneity. These insights have led to the elucidation of the mechanisms that drive the increased severity of childhood-onset SLE and point towards new pathways for personalized therapeutic approaches aimed at improving long-term outcomes and quality of life for patients.

Key points

  • Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset SLE, with earlier disease onset, more organ involvement, and higher morbidity and mortality.

  • Genetic and epigenetic studies in childhood-onset SLE have revealed age-enriched mechanisms, including monogenic and polygenic contributions, with heightened type I interferon signalling and impaired apoptotic body clearance having central roles.

  • Immune profiling technologies have enabled unique immune cell signatures and organ-specific inflammation patterns to be uncovered in childhood-onset SLE, advancing understanding of disease mechanisms and heterogeneity to guide future precision medicine strategies.

  • Novel biomarkers, notably urinary, lipid and neuroinflammatory markers, have shown promise for early detection and monitoring of lupus nephritis, cardiovascular disease and central nervous system involvement in childhood-onset SLE.

  • Treatments for childhood-onset SLE increasingly include biologic drugs and targeted therapies, although access remains limited; ongoing trials and approval of paediatric-specific treatments and guidelines are essential for therapeutic equity.

  • Future research must prioritize inclusive, multi-ethnic studies, age-specific diagnostic consideration and expanded paediatric clinical trial infrastructure to enable personalized, equitable care for children with childhood-onset SLE.

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Fig. 1: Blood and tissue immune phenotypes in childhood-onset SLE.
Fig. 2: Mechanisms of exacerbated type I IFN signalling in childhood-onset SLE pathogenesis.
Fig. 3: Major advances in childhood-onset SLE in the past decade.

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Acknowledgements

G.A.R. was supported by an Arthritis UK Career Development Fellowship (22856). C.C. was supported by a National Institute of Heath Research (NIHR) University College London Hospital (UCLH) Biomedical Research Centre (ref. BRC4/III/CC) grant. A.K. was supported by a Canadian Institutes of Health Research Canada Research Chair Tier 2 and Lupus Research Alliance Career Development Award.

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Authors and Affiliations

  1. Department of Ageing, Rheumatology and Regenerative Medicine, Division of Medicine, University College London, London, UK

    George A. Robinson, David A. Isenberg & Coziana Ciurtin

  2. Department of Pediatrics, Division of Rheumatology, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

    Andrea Knight

  3. Division of Rheumatology, Department of Pediatrics, British Columbia Children’s Hospital & University of British Columbia, Vancouver, British Columbia, Canada

    Lori B. Tucker

  4. Department of Pediatrics Nephrology, Rheumatology and Dermatology, Femme-Mère-Enfant Hospital, Hospices Civils de Lyon, Bron, France

    Alexandre Belot

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G.A.R., C.C., D.A.I. and A.B. researched data for the article. G.A.R., C.C. and D.A.I. contributed substantially to discussion of the content. All authors wrote the article and reviewed and/or edited the manuscript before submission.

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Robinson, G.A., Knight, A., Tucker, L.B. et al. Insights into the pathogenesis of childhood-onset SLE in the past decade. Nat Rev Rheumatol 22, 26–41 (2026). https://doi.org/10.1038/s41584-025-01321-x

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