Presenter details potential treatment pathways for central nervous system, neuropsychiatric systemic lupus

DESTIN, Fla. — A speaker at the Congress of Clinical Rheumatology Annual Meeting presented new insights in the identification of inflammatory mechanisms for potential therapeutic targets and endpoints in central nervous system lupus and neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) includes a variety of focal, diffuse, central, peripheral, psychiatric, isolated, complex, simultaneous and sequential symptoms that represent active and inactive disease states. Central nervous system lupus (CNS) can include antiphospholipid syndrome, vasculitis, antibody-mediated neuronal toxicity, metabolic disturbance, stroke and infection.

“The goal was to review biologic components of learning and memory consolidation, including neuroimmune interactions that support synaptic plasticity and adult neurogenesis,” 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, 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.”

Mackay and a team of researchers examined patients’ performance on the Rey-Osterrieth Complex Figure Test, a neuropsychological assessment in which subjects reproduce a complicated line drawing; and on the Spatial Navigation Task, a maze assessment that tests visuospatial navigation. Investigators also assessed adult neurogenesis and immune signaling data on the patients.

Findings showed anti-ribosomal P antibody binding caused Ca++ influx and apoptotic death of neurons, and neuronal surface P antigen influenced glutamatergic synaptic transmission and plasticity in the hippocampus.

Findings also showed anti-NMDAR antibodies mediated behavioral disturbances via amygdala effects, and anti-P antibodies affected depression and hyposmia through effects in the cingulate and olfactory piriform cortices. Separate mechanisms and effects on NMDAR and AMPAR activity and LTP suggest anti-P antibodies may potentiate effects of anti-NMDAR antibodies.

Mackay said unrestrained acute and chronic inflammation with circulating inflammatory cytokines and oxidative stress can have deleterious effects on cognition, mood and fatigue. She added that brain reactive autoantibodies can mediate cognitive dysfunction and behavior through neuronal toxicity and effects on synaptic plasticity.

“Not all therapies need to be immunosuppressive, as evidenced by success in fish oil for antioxidant properties and fatigue in systemic lupus erythematosus,” she said. “Consideration of known and emerging neuroinflammatory mechanisms of biologic processes underlying NPSLE syndromes will direct us to therapeutic targets and potential biomarkers.”

She said anticytokine therapies may provide benefits through centrally mediated processes unrelated to effects on peripheral organs. Clinical trials of neuroprotection await identifications of sensitive and specific biomarkers for neuropsychiatric symptoms, she said. – by Shawn M. Carter

Reference:

Mackay M, et al. New insights into CNS lupus. Presented at: Congress of Clinical Rheumatology Annual Meeting; May 12-15, 2015; Destin, Fla.

Disclosure: Mackay reports no relevant financial disclosures.