Sjögren’s is a chronic autoimmune disease characterized by dry mouth and eyes, fatigue, and musculoskeletal pain resulting from the attack of the moisture-producing glands by the body’s own white blood cells. The subject invention is based on the discovery of an association between infection by a novel clade 1 variant of hepatitis delta virus (HDV) and primary Sjögren’s syndrome. The association was made after detection of the HDV nucleic acid in the salivary glands of patients diagnosed with Sjögren’s syndrome and in vivo studies in mice that developed Sjögren’s syndrome-like pathogenesis after expression of HDV antigen. The discovery of this link opens the possibilities for developing diagnostics against HDV to determine who are at risk for developing Sjögren’s syndrome. The novel HDV variant can also serve as a potential therapeutic target for preventing or treating Sjögren’s.