Stanford University

Steinman Laboratory

Dr. Lawrence Steinman

Principal Investigator: Dr. Lawrence Steinman

Project Title: Potential Biomarkers for disease activity
in NMO

Winner of the 2011 Charcot Award

Neuromyelitis Optica (NMO) is an autoimmune demyelinating disease which dominantly targets optic nerves and spinal cord of the central nervous system (CNS). Over 80% of the NMO patients have relapses causing permanent neurologic disability. The relapse rate in 1-year is 60% and in 3-year is 90%. Relapses still occur even while patients are treated with immune modulatory therapies. Thus, reliable biomarkers predicting relapses and response to therapy are urgently needed in the management of NMO patients.

The pathogenesis of NMO is largely unraveled by the discovery of NMO-IgG, a set of auto-antibodies in NMO that target a water channel aquaporin-4 (AQP4), which is expressed on the foot process of astrocytes in CNS. The presence of NMO-IgG induces the complement activation which leads to death of astrocytes. Astrocytes play a crucial role in transporting nutrition to other neuronal cells; and its foot process composes part of blood-brain barrier. Thus the compromise of astrocytes results in infiltration of other immune cells and the onset of demyelination and neural tissue damage.

In this study, Stanford will assess the potential of biomarkers in relation to disease activity in NMO by utilizing two multichannel platforms—flow cytometry and multiplex luminex cytokine analysis. They will investigate 1) pathogenic B cells that express NMO-IgG and 2) cytokines/chemokines that regulate the activation and traffic of immune cells.

The Stanford University NMO Team

  • Lawrence Steinman, MD George A. Zimmerman Prof. of Neurology, Pediatrics and Genetics, Chair Interdepartmental Program in Immunology
  • May Han, MD Senior Fellow in Neuroimmunology; Acting Assistant Professor of Neurology and Neurological Sciences
  • William R. Robinson, MD PhD Assistant Professor of Medicine