Sjögren's syndrome: immunobiology of exocrine gland dysfunction

Sjögren's syndrome is an autoimmune disorder characterized by dryness of the eyes and mouth. The frequency of this disorder remains controversial, due to absence of a universally accepted classification system. In the San Diego and San Francisco classification systems for primary Sjögren's syndrome, evidence for an autoimmune process and focal lymphocytic infiltration of the salivary or lacrimal gland is required for diagnosis. This paper reviews the genetic and environmental factors that have been associated with the autoimmune process in Sjögren's syndrome. Key immunopathologic features include: (a) an increased prevalence of particular HLA-DR/DQ alleles; (b) induction of HLA-DR/DQ proteins on the epithelial cells in salivary and lacrimal gland biopsies; (c) infiltration of the glands by CD4+ T-cells that transcribe IL-2 and IFN-gamma; (d) induction of granzyme A and perforin in CD4+ T-cells, suggesting a mechanism of cellular destruction of the glands; (e) clonal expansion of B-cells that use a particular light chain within the salivary gland; (f) production of autoantibodies against nuclear antigens SS-A (60 and 52 kDa) and SS-B (48 kDa), indicating a failure of normal tolerance mechanisms; and (g) increased frequency of B-cell non-Hodgkin's lymphoma. Indirect evidence has suggested a potential role for viruses (especially members of the herpesvirus and retroviral family) as co-factors.