Identification of novel autoantigens using human IgG in SCID mice implanted with lacrimal and salivary grands from patients with Sjogren's Syndrome

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Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by chronic lymphocytic infiltration of the exocrine glands and a worldwide disease with higher prevalence in woman. The salivary and lacrimal glands are the main targets of this lymphocytic infiltration, which as a consequence leads to tissue destruction and decreased function of these glands. But the etiology of SS and mechanisms of lymphocytic infiltration is unknown. The purpose of our project was the identification of specific autoantigens contributing to the disease pathogenesis and progression in SS and useful serological markers for the clinical diagnosis of SS. We demonstrated that the implant of nondisrupted pieces of fresh salivary and lacrimal glands biopsy tissue from patients with SS into the subcutis of SCID mice results in high levels of human IgG (44-3,426μg/ml) produced by gland-infiltrated B and plasma cells in the sera of 20 % mice inoculated with gland biopsy tissue. Using the sera including human IgG from these SCID mice, we demonstrated the cDNA expression cloning analysis with two human salivary gland epithelial cell lines (HSG and HSY) and normal human submandibular grand tissue cDNA libraries in order to identify novel autoantigens as serological marker. The clone encoded SS-A/Ro and SS-B/La, known as a major target of autoantibodies in SS, had the most phage clones isolated by this analysis. To further select the specific autoantigens in SS, we carried out serological screenings using the sera of patients with SS and healthy individuals. Frequencies of IgG autoantibodies against five newerly isolated autoantigens in the sera of patients with SS showed between 30 % and 45 % in significantly higher amounts than in sera from healthy individuals. These results were suggested that our approach using SCID mice may allow the identification of novel specific autoantigens as serological markers for the clinical diagnosis of SS.