DEFINITION, INCIDENCE, AND PREVALENCE
Sjögren's syndrome is a chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration of the exocrine glands resulting in xerostomia and dry eyes. Approximately one-third of patients present with systemic manifestations; a small but significant number of patients develop malignant lymphoma. The disease presents alone (primary Sjögren's syndrome) or in association with other autoimmune rheumatic diseases (secondary Sjögren's syndrome) (Table 383-1).
Middle-aged women (female-to-male ratio, 9:1) are primarily affected, although Sjögren's syndrome may occur at any age, including childhood. The prevalence of primary Sjögren's syndrome is ~0.5–1%, while 30% of patients with autoimmune rheumatic diseases suffer from secondary Sjögren's syndrome.
Sjögren's syndrome is characterized by both lymphocytic infiltration of the exocrine glands and B lymphocyte hyperreactivity. An oligomonoclonal B cell process, which is characterized by cryoprecipitable monoclonal immunoglobulins (IgM?) with rheumatoid factor activity, is evident in up to 25% of patients.
Sera from patients with Sjögren's syndrome often contain autoantibodies to non-organ-specific antigens such as immunoglobulins (rheumatoid factors) and extractable nuclear and cytoplasmic antigens (Ro/SS-A, La/SS-B). Ro/SS-A autoantigen consists of two polypeptides (52 and 60 kDa, respectively) in conjunction with cytoplasmic RNAs, whereas the 48-kDa La/SS-B protein is bound to RNA III polymerase transcripts. Autoantibodies to Ro/SS-A and La/SS-B antigens are usually detected at the time of diagnosis and are associated with earlier disease onset, longer disease duration, salivary gland enlargement, and more intense lymphocytic infiltration of minor salivary glands.
The major infiltrating cells in the affected exocrine glands are activated T and B lymphocytes. T cells predominate in mild lesions, whereas B cells are dominant in more severe lesions. Macrophages and dendritic cells also are found. The number of macrophages positive for interleukin (IL) 18 has been shown to correlate with parotid gland enlargement and low levels of the C4 component of complement, both of which are adverse predictors for lymphoma development.
Ductal and acinar epithelial cells appear to play a significant role in the initiation and perpetuation of autoimmune injury. These cells (1) express class II major histocompatibility complex (MHC) molecules, costimulatory molecules, and abberant expression of intracellular autoantigens on cell membranes and thus are able to provide signals essential for lymphocytic activation; (2) inappropriately produce proinflammatory cytokines and lymphoattractant chemokines necessary for sustaining the autoimmune lesion and allowing progression to more sophisticated ectopic germinal center formation, which occurs in one-fifth of patients; and (3) express functional receptors of innate immunity, particularly Toll-like receptors (TLRs) 3, 7, and 9, that may account for the perpetuation of the autoimmune response.
TABLE 383-1Association of Sjögren's Syndrome with Other Autoimmune Diseases ||Download (.pdf) TABLE 383-1 Association of Sjögren's Syndrome with Other Autoimmune Diseases
Systemic lupus erythematosus
Mixed connective tissue disease
Primary biliary cirrhosis
Chronic active hepatitis