BACKGROUND Behcet's disease (BD) is an autoinflammatory disease with unclear pathogenesis. The oral and vascular tissue are the main target organs in BD. The role of humoral immunity in pathogenesis of oral and vascular lesions in BD patients has not been well studied. Therefore, the aim of this study was to investigate the presence of autoantibodies in the sera of BD patients using oral and vascular tissue related cell lines. METHODS Proteins from oral (KB, HGF-1) and vascular (HUVEC) related cell lines as well as C2C12 (a muscle myoblast cell line) were extracted as representatives of oral and vascular tissue antigens and the presence of autoantibodies in BD's sera were investigated using high throughput two dimensional electrophoresis (2DE) and immunoblotting techniques. Sera of other autoimmune diseases (RA and SLE) and normal individuals were used as controls. RESULTS After silver staining of 2DE gels, 2831, 2195, 1732, and 1839 spots were detectable in the proteome map of HUVEC, KB, HGF-1, and C2C12 cell lines, respectively. The majority of spots were in the pH range of 5 - 8 and the molecular weight range of 14 - 66 Kd. The immunoreactivity of BD, RA, SLE, and normal sera were not different with separated proteins of the cell lines. CONCLUSIONS According to our results, it seems that humoral immunity is not significantly involved in BD pathogenesis. Therefore, investigation of the role of cellular immunity, especially TH1 and TH17 cells and their cytokine profiles, in the pathogenesis of BD is recommended for future studies.