Antibodies and the brain: anti-N-methyl-D-aspartate receptor antibody and the clinical effects in patients with systemic lupus erythematosus

Purpose of review Neuropsychiatric manifestations are one of the fatal complications in patients with systemic lupus erythematosus (SLE). However, the diagnosis and monitoring of that aspect of SLE is still challenging, as there are no reliable biomarkers linked to central nervous system (CNS) damage. This review emphasizes potential candidate autoantibodies that appear to be associated with development of behavioral and psychiatric manifestations in SLE patients. Recent findings Developments in the pathogenesis in SLE, not surprising for this immune disorder, point to specific, autoantibody toxicity. Namely, the discovery of an antibody which reacts with DNA and with the extracellular domain of N-methyl-D-aspartate (NMDA) receptor subunit GluN2A and 2B (anti-NMDA), an important receptor on neurons that is ubiquitous in the CNS, may lead to new insights into the behavioral and psychiatric manifestations in SLE. These anti-NMDA antibodies induce neuronal apoptosis and degeneration of surviving neurons in murine models. This functional antibody is also detected in SLE patients who have behavioral and psychiatric manifestations. The presence of anti-NMDA in cerebrospinal fluid but not in serum is associated significantly with overwhelming CNS abnormalities, suggesting importance of direct access of autoantibodies to brain dysfunction. Summary As anti-NMDA autoantibodies are present in patients who develop psychiatric manifestations in SLE, it is possible that novel therapeutic approaches will depend on altering the activity of these autoantibodies.