**2. Pathophysiology**

Primary Sjögren's syndrome is a multifactorial disorder including genetic predisposition, hormonal, and environmental factors [6, 13]. The pathogenesis of SS is incompletely understood. For years, it has been considered as T-cell dependent autoimmune response; now, the role of B cells is also described and is known as important. Tissue destruction is associated with the infiltration by both activated T and autoreactive B cells [1, 4, 6].

Plasmacytoid dendritic cells produce interferon (IFN)-I responsible for apoptosis/necrosis of glandular epithelial cells—it upregulates the major histocompatibility complex (MHC) molecules (class I and II) and costimulatory molecules (CD80,CD86), promotes production of cytokines (interleukin IL-6, IL-10, IL-12, IL-15, IF-γ, tissue growth factor TGF-β, tumor necrosis factor TNF-α), and chemokines (CXCL-11, CXCL-12, CXCL-13, CXCL-21) responsible for leukocytes migration resulting activation of the inflammatory reaction [1, 4, 6, 14, 15].

Glandular epithelial cells' necrosis/apoptosis reveals Sjögren-specific antibodies A (SSA, anti-RO) and B (SSB, anti-La)—though the role of these autoantigens is not completely clear, but the presence of them is one of the diagnostic criteria of pSS [1, 4]. Moreover, the presence of macrophage-derived chemokine (MDC) and thymus-activation-regulated chemokine (TARC), abnormal distribution of aquaporin (AQP)-5 cell membrane transporter, and defect in AQP-5 trafficking increased B-cell-activating factor (BAFF) and the matrix metalloproteinases (MMP) level were described in relationship with tissue damage in pSS [1, 4, 15–17].

Autoantibodies against type-3 muscarinic acetylcholine receptors are the suggested reason of peripheral neuropathies (PN) associated with SS though it has not been proved yet [6, 18].
