Internalization of Anti-DNA Antibodies by Rat Brain Cells: A Possible Pathogenetic Mechanism of Neuropsychiatric Lupus

Accumulating evidence suggests that DNA-anti-DNA antibody immune complexes are endocytosed by cells, where they ligate intracellular nucleic acid sensors. This results in production of type I interferon or other cytokines, which may be a significant pathogenetic mechanism systemic lupus erythematosus (SLE). Most studies thus far have been performed using cell-lines peripheral blood mononuclear but it remains unclear whether cells from the brain can take up such complexes. Because permeability blood-brain interfaces is suggested to increased and autoantibodies detected cerebrospinal fluid SLE patients with neuropsychiatric manifestations, we hypothesize internalized central nervous system cause dysregulation neural networks. As first step test this hypothesis, here investigated anti-DNA antibodies live vitro. Primary culture rat astrocytes were incubated for 1 h at 37°C without monoclonal antibodies. After washing, fixation, permeabilization blocking, fluorescent labeled second antibody. We observed dsDNA-specific entered nucleus, while cross-reactive phospholipid DNA cytoplasm. Isotype-matched control IgG did not enter suggesting viable cell membrane nuclear intact time. When 4°C, internalization was almost completely abolished. passive transfer an energy-dependent process. Given play indispensable roles maintaining function networks, these provide novel perspective on mechanisms manifestations often presented SLE.