Taming lupus—a new understanding of pathogenesis is leading to clinical advances

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the loss of tolerance to nuclear self antigens, the production of pathogenic autoantibodies and damage to multiple organ systems. Over the years, patients with SLE have been managed largely with empiric immunosuppressive therapies, which are associated with substantial toxicities and do not always provide adequate control of the disease. The development of targeted therapies that specifically address disease pathogenesis or progression has lagged, largely because of the complex and heterogeneous nature of the disease, as well as difficulties in designing uniform outcome measures for clinical trials. Recent advances that could improve the treatment of SLE include the identification of genetic variations that influence the risk of developing the disease, an enhanced understanding of innate and adaptive immune activation and regulation of tolerance, dissection of immune cell activation and inflammatory pathways and elucidation of mechanisms and markers of tissue damage. These discoveries, together with improvements in clinical trial design, form a platform from which to launch the development of a new generation of lupus therapies.

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Figure 1: The spiral of disease progression in SLE.
Figure 2: The role of SLE risk alleles in the pathogenesis of SLE.
Figure 3: Recognition of nucleic acids by innate immune cells triggers cytokine production.
Figure 4: Mechanisms for organ damage.

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Acknowledgements

This work was supported by US National Institutes of Health grants R01 DK085241-01, R01 AI083901 and R21 AR057930. The authors thank T. Rothstein and A. Boneparth for critical reading of the manuscript.

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Correspondence to Anne Davidson.

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Liu, Z., Davidson, A. Taming lupus—a new understanding of pathogenesis is leading to clinical advances. Nat Med 18, 871–882 (2012). https://doi.org/10.1038/nm.2752

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