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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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 languageAmerican English
Pages (from-to)34-44
Number of pages11
JournalJournal of Autoimmunity
StatePublished - Jul 2018

Bibliographical note

Funding Information:
These studies were supported by research grants from the Abisch-Frenkel Foundation ( 15/H1 ) and the Leona M. and Harry B. Helmsley Charitable Trust ( 2015PG-ISL007 ) to A. Ben-Zvi; a RO1 grant from the National Institute of Arthritis and Musculoskeletal Diseases ( AR065594 ) to C. Putterman; and training grant T32-GM007288 to A. Stock from the NIH .

Publisher Copyright:
© 2018 Elsevier Ltd


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


Dive into the research topics of 'Mechanisms of neuropsychiatric lupus: The relative roles of the blood-cerebrospinal fluid barrier versus blood-brain barrier'. Together they form a unique fingerprint.

Cite this