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 may develop malignant lymphoma. The disease presents alone (primary Sjögren's syndrome) or in association with other autoimmune rheumatic diseases (secondary Sjögren's syndrome) (Table 324-1).
Table 324-1 Association of Sjögren's Syndrome with Other Autoimmune Diseases |Favorite Table|Download (.pdf)
Table 324-1 Association of Sjögren's Syndrome with Other Autoimmune Diseases
Systemic lupus erythematosus
Mixed connective tissue disease
Primary biliary cirrhosis
Chronic active hepatitis
Middle-aged women (female-to-male ratio, 9:1) are primarily affected, although it may occur in all ages, including childhood. The prevalence of primary Sjögren's syndrome is approximately 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 (IgMκ) with rheumatoid factor activity, is evident in up to 25% of patients.
Sera of patients with Sjögren's syndrome often contain autoantibodies directed against 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) 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, more severe lymphocytic infiltration of minor salivary glands, and certain extraglandular manifestations. Antibodies to α-fodrin (120 kDa), a salivary gland–specific protein, as well as muscarinic receptor 3 (M3R) also have been found in sera of patients with Sjögren's syndrome. The major infiltrating cells in the affected exocrine glands are activated T and B lymphocytes. T cells predominate in mild lesions, whereas B-cells in more severe lesions. T regulatory cells also have been detected. Macrophages and dendritic cells also are found. The number of interleukin (IL)-18 positive macrophages has been shown to correlate with parotid gland enlargement and low levels of the C4 component of complement, both adverse predictors for lymphoma development. Glandular epithelial cells undergo apoptotic death by signals provided from T cells. Infiltrating lymphocytes not only provide apoptotic messages to epithelial cells but also tend to be resistant to apoptosis. Ductal and acinar epithelial cells appear to play a significant role in the initiation and perpetuation of the autoimmune injury. They express class II major histocompatibility complex (MHC), costimulatory molecules, and intracellular autoantigens expressed on cell membranes, thus being able to provide signals essential for lymphocytic activation. Finally, they inappropriately produce proinflammatory cytokines and lymphoattractant chemokines necessary for sustaining the autoimmune lesion and progressing to more sophisticated ectopic germinal center formation, ...