What are the latest clinical findings regarding the association of neurotoxic brain antibodies found in the cerebrospinal fluid in patients with autoimmune disorders?

Purpose of review Recently, experiments show that the autoantibodies with direct access to neurons following blood brain barrier (BBB) disruption destroy neurons and lead to remodeling in damaged neurons. These are critical steps in autoantibody-mediated central nervous system disorder called neuropsychiatric syndromes in systemic lupus erythematosus (NPSLE). The purpose of this review is to examine therapeutic opportunities to repress neuronal remodeling by microglia after acute neuronal injury by autoantibodies. Recent findings Recent studies have demonstrated that BBB disruption is a critical step for developing NPSLE, and serum anti-Sm antibodies have been significantly associated with BBB breakdown. In addition, it has been reported that antiglucose regulated protein-78 in patients with SLE also disrupt the BBB. Experiments with anti-N-methyl-d-aspartate antibodies show that HMGB1 and C1q were essential to activate microglia which, in turn, remodel damaged neuronsin vivo. Interestingly treatment with angiotensin-converting enzyme inhibitor inactivated microglia and blunted neuronal remodeling as well as positively affected behavioral abnormalities. BBB disruption, acute neuronal damage and neuronal remodeling by activated microglia are all critical steps for NPSLE development, and each step will afford novel therapeutic targets.