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

Sivan Gelb, Ariel D. Stock, Shira Anzi, Chaim Putterman, Ayal Ben-Zvi

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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/fas lpr/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.

Original languageEnglish (US)
Pages (from-to)34-44
Number of pages11
JournalJournal of Autoimmunity
Volume91
DOIs
StatePublished - Jul 2018

Keywords

  • Autoantibodies
  • Blood-CSF barrier (BCSFB)
  • Blood-brain barrier (BBB)
  • Choroid plexus (CP)
  • Lupus
  • Neuropsychiatric-lupus (NPSLE)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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