Mechanisms of neuropsychiatric lupus: The relative roles of the blood-cerebrospinal fluid barrier versus blood-brain barrier

J Autoimmun. 2018 Jul:91:34-44. doi: 10.1016/j.jaut.2018.03.001. Epub 2018 Apr 4.


The pathogenesis of neuropsychiatric lupus (NPSLE) is believed to include the entry of circulating neuropathic antibodies to the brain via a pathologically permeable blood-brain barrier (BBB). Nevertheless, direct evidence of BBB pathology or mechanisms underlying BBB dysfunction is missing. Here, we examined BBB integrity in an established NPSLE mouse model (MRL/faslpr/lpr). Surprisingly, challenging the barrier with various exogenous tracers demonstrated insignificant changes in BBB permeability. Furthermore, electron microscopy showed no ultrastructure changes supporting hyper-permeability. However, we found that abnormal function of the blood-cerebrospinal fluid barrier (BCSFB) in the choroid plexus underlies brain exposure to neuropathic antibodies. Considerable intrathecal lymphocyte infiltration likely occurs through the BCSFB, accompanied by epithelial hyper-permeability to antibodies. Our results challenge the commonly held view of BBB disruption in NPSLE, supporting a shift in focus to BCSFB dysfunction as a causative factor in the disease.

Keywords: Autoantibodies; Blood-CSF barrier (BCSFB); Blood-brain barrier (BBB); Choroid plexus (CP); Lupus; Neuropsychiatric-lupus (NPSLE).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / metabolism
  • Blood-Brain Barrier
  • Brain / immunology*
  • Brain / pathology
  • Cell Movement
  • Cerebrospinal Fluid
  • Choroid Plexus / immunology*
  • Disease Models, Animal
  • Epithelium / pathology*
  • Female
  • Humans
  • Lupus Vasculitis, Central Nervous System / immunology*
  • Lupus Vasculitis, Central Nervous System / pathology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred MRL lpr
  • Mutation / genetics
  • Permeability
  • fas Receptor / genetics


  • Autoantibodies
  • fas Receptor