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The microbiome and HLA-B27-associated acute anterior uveitis

Abstract

Acute anterior uveitis (AAU) and the spondyloarthritis (SpA) subtypes ankylosing spondylitis, reactive arthritis and psoriatic arthritis are among the inflammatory diseases affected by the biology of the intestinal microbiome. In this Review, the relationship between AAU, SpA and the microbiome is discussed, with a focus on the major SpA risk gene HLA-B*27 and how it is associated with both intestinal tolerance and the loss of ocular immune privilege that can accompany AAU. We provide four potential mechanisms to account for how dysbiosis, barrier function and immune response contribute to the development of ocular inflammation and the pathogenesis of AAU. Finally, potential therapeutic avenues to target the microbiota for the clinical management of AAU and SpA are outlined.

Key points

  • Acute anterior uveitis (AAU) is the most common, clinically apparent, extra-articular manifestation of ankylosing spondylitis.

  • Both AAU and ankylosing spondylitis are strongly associated with HLA-B27.

  • HLA-B27 affects the composition of the gut microbiome, which in turn can modify the immune system and thereby affect health and disease.

  • The intestinal microbiome is strongly implicated in the pathogenesis of AAU and ankylosing spondylitis.

  • Although the mechanisms by which the intestinal microbiome cause AAU and ankylosing spondylitis are incompletely understood, a great potential exists to treat or prevent ankylosing spondylitis and AAU by altering the microbiome.

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Fig. 1: Uveitis subtyping by affected site.
Fig. 2: Frequency of uveitis in patients with spondyloarthritis.
Fig. 3: Disease manifestations of spondyloarthritis.
Fig. 4: Potential mechanisms of microbiome-mediated uveitis.
Fig. 5: Therapeutic strategies to target intestinal microbiota.

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Acknowledgements

The work of the authors was supported by NIH Grants EY026572 to J.T.R., and EY029266 to M.A. and J.T.R., the Spondylitis Association of America to M.A., the William and Mary Bauman Foundation to J.T.R., the Stan and Madelle Family Trust to J.T.R., the Rheumatology Research Foundation to J.T.R. and M.A. and Research to Prevent Blindness to J.T.R. The authors wish to acknowledge many valuable contributions made by the research community that were omitted owing to space to constraints.

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Nature Reviews Rheumatology thanks J. Scher and J. Forrester for their contribution to the peer review of this work.

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Glossary

Masquerade syndromes

Forms of uveitis that clinically mimic inflammation although inflammation is not the primary cause. Examples include a malignancy such as lymphoma or retinoblastoma, retinal degeneration or retinal detachment.

Molecular mimicry

The induction of autoimmunity caused by a non-self-antigen, such as one derived from a bacteria or virus, that resembles a self-antigen sufficiently such that an autoimmune response is induced.

Tachyphylaxis

In pharmacology, the reduced response to a chemical, such as an opioid, resulting from repeated exposure. Continuous or repetitive exposure to bacterial products such as LPS or peptidoglycan results in tachyphylaxis or reduced inflammation.

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Rosenbaum, J.T., Asquith, M. The microbiome and HLA-B27-associated acute anterior uveitis. Nat Rev Rheumatol 14, 704–713 (2018). https://doi.org/10.1038/s41584-018-0097-2

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