Pathogenesis: Harrisons' 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 or IgAκ) with rheumatoid factor activity, is evident in up to 10% of patients. 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. The major infiltrating cells in the affected exocrine glands are activated T lymphocytes in mild lesions, whereas B cells prevail in severe lesions. Macrophages and dendritic cells are also found. The number of macrophages positive for interleukin (IL) 18 has been shown to be associated with parotid gland enlargement and low serum 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 costimulatory molecules, and inappropriately the intracellular autoantigens Ro/SS-A and La/SS-B on their membranes, acquiring the capacity to provide signals essential for lymphocytic activation; (2) produce proinflammatory cytokines and lymphocyte attracting chemokines necessary for sustaining the autoimmune lesion and allowing the formation of ectopic germinal centers, a finding predicting lymphoma development; and (3) express functional receptors of innate immunity, particularly Toll-like receptors (TLRs) 3, 7, and 9, molecules which may account for the initiation of the autoimmune reactivity.
Diagnosis : Harrisons' TABLE 354-5Revised International Classification Criteria for Sjögren’s Syndromea,b,c
aExclusion criteria: past head and neck radiation treatment, hepatitis C infection, AIDS, preexisting lymphoma, sarcoidosis, graft-versus-host disease, use of anticholinergic drugs. bPrimary Sjögren’s syndrome: any four of the six items, as long as item IV (histopathology) or VI (serology) is positive; or any three of the four objective-criteria items (III, IV, V, VI). cIn patients with a potentially associated disease (e.g., another well-defined connective tissue disease), the presence of item I or item II plus any two from among items III, IV, and V may be considered indicative of secondary Sjögren’s syndrome.
Treatment:
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Rheumatology >