Sex differences in Sjögren's syndrome: a comprehensive review of immune mechanisms

Abstract

Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women. Sjögren's syndrome (SS) is an AD that occurs predominately in women over men (16:1). The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth. The disease is believed to be mediated by an inflammatory and autoantibody response directed against salivary and lacrimal gland tissues. This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren's syndrome in order to gain a better understanding of disease pathogenesis.

Keywords: Autoantibodies; Autoimmune disease; Inflammation; Lymphoma; Sex differences; Sjögren’s syndrome.

Fig. 1

Possible role of estrogen in promoting Sjögren’s syndrome. In the context of genetic, epigenetic, and environmental influences like infections and chemicals, the rapid decline in estrogen (E2) levels prior to menopause leads to reduced glandular cell health. Death of glandular cells via apoptosis/necrosis provides self-antigens like nuclear antigens for presentation to the immune system to promote autoimmune disease. At the same time, the protective effects of higher estrogen levels on inflammation disappear allowing increased activation of innate immune pathways like toll-like receptor 4 (TLR4) and NFκB. In contrast, low levels of estrogen continue to increase the level and different types of autoantibodies with age