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.
Bibliographical noteFunding 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 .
© 2018 Elsevier Ltd
- Blood-CSF barrier (BCSFB)
- Blood-brain barrier (BBB)
- Choroid plexus (CP)
- Neuropsychiatric-lupus (NPSLE)