Primary Sjögren's syndrome: current and emergent aetiopathogenic concepts.

Sjögren’s syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes due to functional impairment of the salivary and lacrimal glands [1, 2]. The common histolopathological feature of all organs affected is a potentially progressive lymphocytic infiltration. Salivary glands are the most studied organs because they are affected in almost all patients and are easily accessible. Microscopic examination of the salivary glands reveals a benign lymphoepithelial lesion, characterized by lymphocytic replacement of the salivary epithelium and the presence of epimyoepithelial islands composed of keratin-containing epithelial cells. The predominant cells in the minor labial salivary gland infiltrates are T cells, with a bias towards CD4þ cells rather than CD8þ suppressor cells (CD4/CD8 ratio of 3:1–5:1). B cells constitute approximately 20% of the total infiltrating population, while natural killer (NK) cells are observed less often (5%) [3]. The aetiopathogenesis of primary SS is probably a sequential, multistep process that leads to selective damage of the exocrine glands, with consequent target organ dysfunction. Although the exact mechanisms involved in this aetiopathogenic process are not well known, the autoimmune origin of the disease (autoimmune epithelitis [4]) is probably the aetiopathogenic hypothesis most commonly postulated in primary SS. In this review we have summarized the current concepts on autoimmune aetiopathogenesis of primary SS and reviewed alternative aetiopathogenic mechanisms that have recently been postulated.