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SYSTEMIC LUPUS ERYTHEMATOSUS IN 2018

The microbiome in SLE pathogenesis

Nature Reviews Rheumatology volume 15, pages 72–74 (2019)Cite this article

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Systemic lupus erythematosus (SLE), the embodiment of a multi-organ autoimmune disease, results from hyperactivation of host-defence pathways and immune recognition of the most fundamental building blocks of life. In 2018, key advances have placed intestinal immunity and dysregulated expansions of candidate pathobionts at the forefront of SLE pathogenesis.

Key advances

  • Pathobiont translocation from the small intestine to the liver in lupus-prone mice, and in a subset of patients with systemic lupus erythematosus (SLE), might drive the expression of interferon-related genes and autoantibody production2.

  • Immune priming to primitive bacterial commensal orthologues of the ribonucleoprotein Ro60 results in both physiological autoimmunity and disease-associated autoimmunity in predisposed individuals4.

  • Patients with SLE had a restricted gut microbiota diversity of similar composition to patients with Sjögren syndrome; by contrast, the oral microbiota composition of these two patient groups differed substantially7.

Systemic lupus erythematosus (SLE) is associated with the dominant hallmarks of a type I interferon-related transcriptome signature and pathological autoimmunity to nucleic acids and nucleoprotein complexes1. The immense range of affected organs and clinical presentations in SLE has led many to wonder whether SLE is truly one disease or actually several diseases. Indeed, genome-wide association studies have identified dozens of associated genomic variations; however, each variant generally conveys only a weak associated risk of disease1. The missing pieces of SLE pathogenesis are presumed to be stochastic factors (that is, bad luck and circumstances) and environmental factors that remain incompletely understood, and any potential unifying mechanisms remain elusive. In 2018, a surge of reports uncovered previously unsuspected relationships between SLE and resident commensal intestinal microbial communities, which might be considered as overlooked internal environmental factors2,3,4.

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Fig. 1: Potential pathobiont mechanisms that contribute to SLE pathogenesis.

References

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Acknowledgements

The author declares that he is supported by grants from the NIH and the Judith and Stewart Colton Autoimmunity Center.

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  1. The Laboratory of B cell immunobiology and the Division of Rheumatology, NYU School of Medicine, New York, NY, USA

    Gregg J. Silverman

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Correspondence to Gregg J. Silverman.

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Silverman, G.J. The microbiome in SLE pathogenesis. Nat Rev Rheumatol 15, 72–74 (2019). https://doi.org/10.1038/s41584-018-0152-z

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