Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment

Ann Rheum Dis. 2020 Dec;79(12):1580-1587. doi: 10.1136/annrheumdis-2020-218004. Epub 2020 Oct 1.

Abstract

Objectives: To examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE).

Methods: A total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage.

Results: Patients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cognitive scores (p=0.02), and with the presence of impairment on one or more cognitive tasks (p=0.01).

Conclusion: Our findings provide evidence for a link between extensive BBB leakage and changes in both brain structure and cognitive function in patients with SLE. Future studies should investigate the mechanisms underlying BBB-mediated cognitive impairment, validate the diagnostic utility of BBB imaging, and determine the potential of targeting the BBB as a therapeutic strategy in patients with SLE.

Keywords: Blood-brain barrier; autoimmunity; cognitive impairment; magnetic resonance imaging; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood-Brain Barrier / pathology*
  • Brain / pathology*
  • Capillary Permeability
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology*
  • Female
  • Gray Matter / pathology*
  • Humans
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged