Development of a Cell Culture System to Detect and Analyze Pathogenicity of Autoantibodies Directed to Nuclear Antigens
Sera of patients with certain rheumatic diseases frequently develop antibodies to nuclear antigens. These antibodies are assumed not to be involved in active disease in patients, as their antigenic epitopes localize inside of cells in the nucleus and should not be available for autoantibodies circulating in the peripheral blood of the patient. During the past few years we have studied the intracellular localization of one of the nuclear antigens known as La protein. We were able to show that this antigen shuttles between the nucleus and the cytoplasm and even to the cell surface. This shuttling occurred, simulating in cell culture just those conditions which are known to induce active disease in patients, including UV irradiation, virus infections, and certain drug treatments. In addition to these “pathogenic” conditions, we observed that the antigenic epitope recognized by anti-La monoclonal antibodies (mabs) developed in our lab is also available on the surface of living cells during transition from the G0 to the G1 phase, as well as on mitotic cells. Based on these observations, we developed a simple and reproducible cell culture system allowing us to prove the hypothesis that the antinuclear antibodies are not an epiphenomenon, as generally assumed, but are directly involved in disease.
KeywordsNuclear Antigen Mitotic Cell Cell Culture System Antigenic Epitope Nuclear Speckle
confocal laser scanning microscopy
fetal calf serum
Herpes simplex virus
extractable nuclear antigen
Unable to display preview. Download preview PDF.