Article Text

Download PDFPDF

Response to: ‘Correspondence on ‘Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment’’ by Pamuk and Hasni
Free
  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. 1Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  2. 2Biomedical Translational Imaging Centre (BIOTIC), Queen Elizabeth ll Health Sciences Centre, Halifax, Nova Scotia, Canada
  3. 3Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada
  4. 4Psychiatry, Psychology & Neuroscience and Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  5. 5Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  6. 6Acquired Brain Injury (Epilepsy Program), Nova Scotia Health Authority, Halifax, Nova Scotia, Guernsey
  7. 7Psychiatry and Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  8. 8Mood Disorders Clinic, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  9. 9Physics, Dalhousie University, Halifax, Nova Scotia, Canada
  10. 10Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  11. 11Research Methods Unit, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  12. 12Cognitive and Brain Sciences, Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel
  13. 13Medicine and Pathology, Queen Elizabeth ll Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
  1. Correspondence to Dr John G Hanly, Queen Elizabeth llHlth Svc Ctr, Halifax B3H 4K4, Canada; john.hanly{at}cdha.nshealth.ca

Statistics from Altmetric.com

We thank Dr Pamuk et al1 for their interest in our work,2 and for providing insights regarding mechanisms that may help explain our findings. Their correspondence highlights the importance of further understanding the processes underlying our main finding: extensive blood-brain barrier (BBB) leakage affects ~25% of patients with systemic lupus erythematosus (SLE) and is linked to smaller grey matter volume and cognitive impairment. We agree that the mechanisms resulting in BBB leakage in SLE remain poorly understood, and that a neuroinflammatory response mediated through the lymphatic system may contribute to BBB pathology.

There is a growing consensus regarding the link between BBB pathology and neuroinflammation,3 and several hypotheses regarding causality have been proposed. Some experimental evidence suggests that autoimmune-inflammatory mechanisms may interact with the BBB through the systemic circulation at the capillary lumen, causing BBB injury that triggers downstream neuroinflammation.4 Acting in an amplification loop, neuroinflammation, in turn, further exacerbates BBB injury.5

As reviewed by Pamuk et al, autoimmune-inflammatory mechanisms may also involve the lymphatic system. Animal data suggest that immune cells from lymphoid structures in the neck may migrate into cerebrospinal fluid (CSF) via lymphatics6 or through the choroid plexus,7 and trigger neuroinflammation from the space surrounding the BBB. According to this hypothesis, injury to the BBB occurs not at the capillary lumen, but at the network of glial lymphatic (glymphatic) clearance channels surrounding medium-sized brain vessels.7

We agree that further research is needed for elucidating the role of the lymphatic system in neuroinflammation, BBB permeability, and neuropsychiatric SLE (NPSLE). One of the major challenges in such research is the lack of established clinical tools for assessing the function of the CNS lymphatic system in living patients. Until such methods are available, we would like to highlight that quantitative assessment of BBB permeability—using dynamic contrast-enhanced MRI—offers an important tool for clinical diagnosis of BBB leakage and for gaining further insight into the role of BBB pathology in NPSLE.

References

Footnotes

  • Handling editor Josef S Smolen

  • Twitter @netphys1

  • Contributors Not applicable.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • 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.

  • Provenance and peer review Commissioned; internally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles