The brain in SLE: mechanisms and detection of injury and therapeutic strategies

Abstract Current therapeutic approaches to neuropsychiatric lupus (NPSLE) are limited and not based on knowledge of disease pathogenesis. Therapeutic advances depend on an appreciation of disease pathogenesis. The first requirement is precise case definition and standardized assessments. It is clear that NPSLE is a heterogeneous group of syndromes resulting from multiple pathogenic processes. As an awareness of SLE manifestations in the central nervous system has increased, mechanistic insights have also increased due to sophisticated studies of animal models, improved neuroimaging techniques, and a growing awareness of brain–immune system interactions. The pathogenesis of NPSLE includes genetic predisposition, cytokines, autoantibodies, microglial dysfunction, and disruption of the blood–brain barrier, but alignment of specific pathways to individual disease manifestations is still in its infancy. While new information has yet to have altered clinical practice, it has begun to identify biomarkers for occult brain pathology and identified new and promising therapeutic targets in patients with NPSLE.