Sjögren's syndrome: autoimmune epithelitis

Abstract

Sjögren's syndrome (SS), the ideal model to study autoimmunity and lymphoid malignancy, is a common chronic disease which in the last 30 years has been studied extensively on clinical and pathophysiological grounds. Clinical studies regarding kidney disease in SS patients have shown that the predominate lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one-fourth of SS patients suffer from subclinical, interstitial lung disease. Reevaluation, however, of the pulmonary disease, using functional, radiologic (including CT-scan), and histopathologic studies, revealed that the lesion starts peribronchially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the majority of extraglandular manifestations of SS are due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the protooncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients, by in situ hybridization, revealed that the mRNA of the proinflammatory cytokines IL-1 and IL-6 also comes from the epithelial cells. Finally, proviral DNA is incorporated in the DNA of epithelial cells. On the basis of these clinical and basic observations, we suggest that the major suffering cell in SS patients is the epithelium and thus we propose this descriptive term "autoimmune epithelitis" instead of "Sjögren's syndrome.