Advances in understanding the pathogenesis of primary Sjögren's syndrome

Nat Rev Rheumatol. 2013 Sep;9(9):544-56. doi: 10.1038/nrrheum.2013.110. Epub 2013 Jul 16.


Primary Sjögren's syndrome (pSS) is a prototypic autoimmune disorder, management of which has long suffered from a lack of knowledge of the underlying pathophysiological mechanisms; however, over the past decade major advances have been made in understanding the pathogenesis of pSS. The innate immune system has been demonstrated to have an important role at the early stage of the disease, notably through activation of the type I interferon (IFN) system. In addition, mechanisms of B-cell activation in pSS have become clearer, particularly owing to recognition of the involvement of the TNF family cytokine B-cell-activating factor, production of which is highly dependent on expression of type I and type II IFNs. Moreover, key inroads have been made in understanding lymphomagenesis, the most severe complication of pSS. IL-12 production and subsequent T-cell activation, mainly IFN-γ-secreting type 1 T-helper cells, have also been implicated in disease pathogenesis. Furthermore, evidence implicates neuroendocrine system dysfunction in pSS pathogenesis. These pathophysiological advances open new avenues of investigation. Indeed, the increased understanding of pSS pathogenesis has already led to the development of promising novel therapeutic strategies. This article summarizes recent findings regarding the pathogenic mechanisms involved in pSS and their implications.

Publication types

  • Review

MeSH terms

  • Humans
  • Immunity, Innate / physiology*
  • Interferon Type I / physiology
  • Interleukin-12 / physiology
  • Lymphocyte Activation / physiology
  • Signal Transduction / physiology
  • Sjogren's Syndrome / etiology*
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / physiopathology*


  • Interferon Type I
  • Interleukin-12