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Etiology and Pathogenesis of Sjögren’s Syndrome with Special Emphasis on the Salivary Glands

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Sjögren’s Syndrome

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Abstract

Pathogenesis from the Greek pathos, “disease,” and genesis, “creation,” is the process by which an etiological factor and subsequent downstream events cause disease. Although in Sjögren’s syndrome (SS), alike for most other autoimmune diseases, the enigma leading to a pathogenic attack against self has not yet been solved, the disease must be mediated by specific immune reactions against somatic cells to qualify as an autoimmune disease. In SS the autoimmune response is greatly directed against the exocrine glands, which, as histopathological hallmark of the disease, display persistent focal mononuclear cell infiltrates. Clinically, the disease in most patients is manifested by two local severe symptoms: dryness of the mouth (xerostomia) and the eyes (keratoconjunctivitis sicca). A number of systemic features have also been described and the presence of autoantibodies against the ubiquitously expressed ribonucleoprotein particles Ro (SSA) and La (SSB) further underlines the systemic nature of SS. The original explanatory concept for the pathogenesis of SS proposed a specific, self-perpetuating, immune-mediated loss of acinar and ductal cells as the principal cause of salivary gland hypofunction. Although straightforward and plausible, the hypothesis, however, falls short of accommodating several SS-related phenomena and experimental findings. Consequently, researchers considered immune-mediated salivary gland dysfunction prior to glandular destruction and atrophy as potential molecular mechanisms underlying the symptoms of dryness in SS. Accordingly, apoptosis, fibrosis, and atrophy of the salivary glands would represent consequences of salivary gland hypofunction. This chapter will also put into perspective research involving the etiology of SS by discussing the results in a broader context along lines drawn by the different basic concepts of immunity.

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Acknowledgements

We thank Dr. B. Delaleu-Justitz for careful revision of the manuscript. Financial support: The European Union (BMH4-CT96-0595; BMH4-CT98-3489; QLK2-1999-51079; QLK2-CT-2001-30115; MEST-CT-2004-514483, MEIF-CT-2007-041083), The Research Council of Norway’s GLOBVAC program, The Strategic Research Program at Helse Bergen (regional health authorities of Western Norway), and The Broegelmann Foundation.

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Authors and Affiliations

  1. Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway

    Nicolas Delaleu

  2. Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece

    Menelaos N. Manoussakis & Haralampos M. Moutsopoulos

  3. Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway

    Roland Jonsson

  4. Department of Rheumatology, Haukeland University Hospital, Bergen, Norway

    Roland Jonsson

  5. Department of Otolaryngology, Head, and Neck Surgery, Haukeland University Hospital, Bergen, Norway

    Roland Jonsson

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  1. Nicolas Delaleu
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  2. Menelaos N. Manoussakis
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  3. Haralampos M. Moutsopoulos
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  4. Roland Jonsson
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Correspondence to Roland Jonsson .

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Editors and Affiliations

  1. Research Foundation, Rheumatology Clinic, Scripps Memorial Hospital &, Caminito Sinnecock 6565, La Jolla, 92037, California, USA

    Robert I. Fox

  2. Research Foundation, Rheumatology Clinic, Scripps Memorial Hospital &, Caminito Sinnecock 6565, La Jolla, 92037, California, USA

    Carla M. Fox

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Delaleu, N., Manoussakis, M.N., Moutsopoulos, H.M., Jonsson, R. (2011). Etiology and Pathogenesis of Sjögren’s Syndrome with Special Emphasis on the Salivary Glands. In: Fox, R., Fox, C. (eds) Sjögren’s Syndrome. Springer, New York, NY. https://doi.org/10.1007/978-1-60327-957-4_15

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