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Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment
  1. Lyna Kamintsky1,
  2. Steven D Beyea2,3,
  3. John D Fisk4,
  4. Javeria A Hashmi5,
  5. Antonina Omisade6,
  6. Cynthia Calkin7,8,
  7. Tim Bardouille9,
  8. Chris Bowen2,3,
  9. Maher Quraan2,3,
  10. Arnold Mitnitski10,
  11. Kara Matheson11,
  12. Alon Friedman1,12,
  13. John G Hanly13
  1. 1 Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  2. 2 Biomedical Translational Imaging Centre (BIOTIC), Queen Elizabeth ll Health Sciences Centre, Halifax, Nova Scotia, Canada
  3. 3 Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada
  4. 4 Psychiatry, Psychology & Neuroscience and Medicine, Dalhousie University and Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  5. 5 Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University and Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  6. 6 Acquired Brain Injury (Epilepsy Program), Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  7. 7 Psychiatry and Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  8. 8 Mood Disorders Clinic, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  9. 9 Physics, Dalhousie University, Halifax, Nova Scotia, Canada
  10. 10 Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  11. 11 Research Methods Unit, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  12. 12 Cognitive and Brain Sciences, Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel
  13. 13 Medicine and Pathology, Queen Elizabeth ll Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
  1. Correspondence to Dr John G Hanly, Division of Rheumatology, Nova Scotia Rehabilitation and Arthritis Center, 1341 Summer Street, Queen Elizabeth ll Hlth Svc Ctr, Halifax, NS B3H 4K4, Canada; john.hanly{at}nshealth.ca

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.

  • systemic lupus erythematosus
  • magnetic resonance imaging
  • autoimmunity
  • Blood-brain barrier
  • cognitive impairment
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Footnotes

  • Handling editor Josef S Smolen

  • Contributors All authors participated in the collection of research data or the data analysis or writing and critical review of the manuscript.

  • Funding This study was supported by the Canadian Institutes of Health Research (CIHR, MOP-88526 and PJT148896), Nova Scotia Health Research Foundation (NSHRF, MED-EST-2015-10067), Natural Sciences and Engineering Research Council of Canada (NSERC, RGPIN 04293-17) and Brain Canada (BC PSG2015-3780), Mitacs grant IT11112 and Nova Scotia Research Fund.

  • Disclaimer The funders of the study had no role in study design, patient recruitment, data collection, analysis, interpretation or publication.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Nova Scotia Health Authority Research Ethics Board, and participants provided written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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