Cognitive Problems in CNS Lupus Affected by Neuroimmune Signaling, Potentially Pointing to Novel Therapies

Disrupted neuroimmune signaling contributes to cognitive problems in neuropsychiatric systemic lupus erythematosus (SLE), according to a study presented at the Congress of Clinical Rheumatology 2016 Annual Meeting, reported by Healio Rheumatology. These new insights into the molecular mechanisms of lupus might provide targets for the development of therapies for lupus affecting the central nervous system (CNS) — a manifestation often not included in drug development attempts.

Neuropsychiatric lupus includes a range of neurological and psychiatric symptoms, but despite its prevalence, it’s not as well studied as lupus manifestations in peripheral organs. It is not known how neuroimmune signaling contributes to cognitive and behavioral problems in these patients.

The study, “New insights into CNS lupus,” was presented by Meggan Mackay, MD, MS, an investigator at the Center for Autoimmune and Musculoskeletal Disease and associate professor at the Feinstein Institute for Medical Research, Molecular Medicine and Medicine at the Hofstra Northshore-LIJ School of Medicine.

“The goal was to review biologic components of learning and memory consolidation, including neuroimmune interactions that support synaptic plasticity and adult neurogenesis,” Mackay said. “We wanted to discuss the effects of altered neuroimmune processes in chronic inflammatory states, such as systemic lupus erythematosus, with attention to cognitive dysfunction, fatigue, and depression.”

The study employed neuropsychological and memory assessment tests and investigated molecular pathways, including the presence of adult neurogenesis, finding that immune disturbances affect synaptic transmission in the hippocampus — a brain region crucial for memory processing. Antibodies targeting glutamate receptors were found to mediate behavioral disturbances.

Mackay also reported other behavioral effects of brain immune signaling processes involving antibodies targeting brain structures, and stated that behavioral and cognitive consequences arise as a result of neuronal toxicity and altered synaptic transmission. The data underscored that persistent inflammation involving the central nervous system takes its toll on cognition, and causes fatigue and altered affective states such as depression.

“Consideration of known and emerging neuroinflammatory mechanisms of biologic processes underlying neuropsychiatric SLE syndromes will direct us to therapeutic targets and potential biomarkers,” Mackay said, underscoring the notion that therapies against specific cytokines might be a promising approach to CNS lupus treatment, an approach that has been on the research agenda for some years and is currently tested in clinical trials.