The influence of sex steroids on Sjögren's syndrome

Sjögren's syndrome is an autoimmune disease affecting the exocrine glands, most typically salivary and lacrimal glands. In Sjögren's syndrome, the acinar cells of these glands are damaged and destroyed, leading to diminished secretion of saliva and tear fluid. Accordingly, the current American-European criteria of Sjögren's syndrome include xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). In addition to these sicca symptoms and signs, the diagnostic criteria require autoimmune features in the form of Sjögren's syndrome SS-A and/or SS-B autoantibodies and lymphocyte infiltrates in labial salivary glands. Majority of patients with Sjögren's syndrome are women and the diagnosis is usually done when they are 40-50 years old. The cause of Sjögren's syndrome is unknown, but taking into account the female dominance and the late onset, our hypothesis is that sex steroids play a key role in the etiology of Sjögren's syndrome. More specifically, we believe that the driving factor behind Sjögren's syndrome could be lack of androgens. It has been shown that patients with Sjögren's syndrome have low concentrations of circulating dehydroepiandrosterone sulfate (DHEA-S) compared to age-matched healthy controls. Our hypothesis is that patients with Sjögren's syndrome suffer from an insufficient local androgen effect in the exocrine target tissues of the disease because of low systemic levels and/or ineffective local intracrine handling of DHEA-S prohormone. To further clarify the role of sex steroids and the eventual deficiency of androgens, salivary glands are studied using protein markers regulated by androgens or estrogens.