The etiopathogenesis of Sjögren's syndrome

With increasing awareness and improved diagnostic tests, Sjögren's syndrome (SS) is becoming recognized as a common autoimmune disease, affecting as many as 3% of women over age 55 years. Apart from keratoconjunctivitis sicca, systemic features are common, leading to considerable morbidity and occasionally mortality. Predisposing factors for SS include HLA determinants that have been linked to DR3 and heterozygosity for DQ-1 and DQ-2. There is accumulating evidence that activated epithelial cells and their interaction with T cells play a central role in pathogenesis. Some restriction of T-cell receptor gene usage to V beta 6.7b and V beta 13.2 and a profile of cytokine production consistent with Th-1-type cells has been observed in affected tissues. Antibodies to Ro (SS-A) and La (SS-B) are found in about 50% of patients and are associated with more severe glandular and extraglandular manifestations. There is evidence that the antibodies are pathogenic, not only in patients, but in their infants born with congenital heart block. Studies of herpesviruses have led to conflicting results, and interest has recently focussed on retroviruses, based on the findings of the expression of retroviral elements in salivary glands of SS patients and antiretrovial antibodies in serum. Mice infected with or transgenic for retroviruses develop SS-like pathology and are currently being studied as animal models of the disease. In the last few years, considerable progress has been made in the understanding of the pathogenesis of SS, and the disease has become the prototype for the investigation of a viral etiology for autoimmune rheumatic disease. Study of its etiopathogenesis may be the key to understanding autoimmune disease in general.