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Mechanisms of Disease: primary Sjögren's syndrome and the type I interferon system

Nature Clinical Practice Rheumatology volume 2, pages 262–269 (2006)Cite this article

Abstract

Sjögren's syndrome is a chronic autoimmune disease of largely unknown etiology and pathogenesis. The salivary and lacrimal glands are the main target organs, and key cells and molecules involved in the autoimmune process have been detected in these glands. Chemokines, expressed by epithelial cells, can attract T cells and dendritic cells that produce proinflammatory cytokines, which stimulate the immune response and induce apoptosis in the acinar and ductal epithelial cells. The autoantigens SSA and SSB are translocated to the apoptotic blebs and trigger infiltrating B cells to produce autoantibodies against SSA and SSB. Germinal-center-like structures can form within glandular lymphocyte foci, facilitating the antigen-driven B-cell activation. Many of the autoimmune mechanisms described above can be induced by type I interferon (IFN), and activation of this system in patients with Sjögren's syndrome has been described. A possible scenario is that an initial viral infection induces type I IFN production in salivary glands with a subsequent activation of the adaptive immune system. Resultant autoantibodies form nucleic-acid-containing immune complexes that can trigger prolonged type I IFN production, leading to a self-perpetuating autoimmune reaction. Several potential therapeutic targets for Sjögren's syndrome exist within the type I IFN system.

Key Points

  • Primary Sjögren's syndrome is a chronic autoimmune disease that affects salivary and lacrimal glands resulting in a sicca syndrome

  • Autoantibodies against nuclear autoantigens and RNA-binding proteins are typically produced in the salivary glands

  • Activation of the type I interferon system has been noted in the salivary glands and this activation might contribute to the disease process

  • The type I interferon production might be caused by immune complexes consisting of autoantibodies, RNA-binding proteins and RNA

  • Inhibition of interferon production might be a new therapeutic option for patients with Sjögren's syndrome

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Figure 1: Minor salivary gland biopsy, stained with hematoxylin-eosin, from a patient with Sjögren's syndrome.
Figure 2: Interferon-α-containing cells (arrows) in the lymphocytic infiltrates in a minor salivary gland biopsy from a patient with primary Sjögren's syndrome.
Figure 3: Production and action of interferon-α in Sjögren´s syndrome.
Figure 4: A disease model of Sjögren's syndrome in a minor salivary gland.

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Acknowledgements

We thank Dr Ullvi Båve, Dr Maija-Leena Eloranta and Tanja Lövgren for valuable scientific contribution and Dr Mike Taussig for valuable comments on the manuscript. This work was supported in part by grants from the Swedish Research Council, the Swedish Rheumatism Foundation, the King Gustaf V 80-year Foundation and the Uppsala University Hospital Research and Development Fund.

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Authors and Affiliations

  1. Consultant Rheumatologist at the Uppsala University Hospital, Uppsala, Sweden

    Gunnel Nordmark

  2. Department of Molecular Biosciences, Swedish University of Agricultural Sciences,

    Gunnar V Alm & Lars Rönnblom

  3. Uppsala University Hospital and Professor of Rheumatology at the Department of Medical Sciences, all at Uppsala University, Uppsala, Sweden

    Gunnar V Alm & Lars Rönnblom

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Correspondence to Lars Rönnblom.

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Competing interests

G Alm and L Rönnblom have received a research grant from Coley Pharmaceutical Group and consulting fees from Miltenyi Biotec. G Nordmark has declared no competing interests.

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Nordmark, G., Alm, G. & Rönnblom, L. Mechanisms of Disease: primary Sjögren's syndrome and the type I interferon system. Nat Rev Rheumatol 2, 262–269 (2006). https://doi.org/10.1038/ncprheum0173

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