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Circulating endothelial cells as potential diagnostic biomarkers in primary central nervous system vasculitis
  1. Milani Deb1,
  2. Stefan Gerdes1,
  3. Meike Heeren1,
  4. Jürgen Lambrecht1,
  5. Hans Worthmann1,
  6. Annemarie Goldbecker1,
  7. Anita Blanka Tryc1,
  8. Svjetlana Lovric2,
  9. Walter Schulz-Schaeffer3,
  10. Almuth Brandis4,
  11. Reinhard Dengler1,
  12. Karin Weissenborn1,
  13. Marion Haubitz2,5
  1. 1Department of Neurology, Hannover Medical School, Hannover, Germany
  2. 2Division of Nephrology, Hannover Medical School, Hannover, Germany
  3. 3Department of Neuropathology, University Medical Center Goettingen, Göttingen, Germany
  4. 4Department of Pathology, Hannover Medical School, Hannover, Germany
  5. 5Division of Nephrology, Klinikum Fulda, Fulda, Germany
  1. Correspondence to Dr Milani Deb, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover D-30625, Germany; deb.milani{at}mh-hannover.de

Abstract

Objective Histological evidence is considered the only proof of primary central nervous system vasculitis (PCNSV). However, brain biopsy is often omitted or delayed because of the invasiveness and possible complications of the procedure. Circulating endothelial cells (CEC) were shown to be elevated in patients with active antineutrophil cytoplasmic antibody-associated vasculitis. We hypothesise that CEC are also elevated in patients with active PCNSV and may contribute to the diagnosis.

Methods CEC were assessed in 18 patients, 3 of whom had biopsy-proven PCNSV and 15 clinical, cerebrospinal fluid and imaging data, highly suggestive of PCNSV. In 3 of these 15 patients CEC assessment was performed after initiation of successful immunosuppressive therapy. CEC numbers of all patients were compared to those of 16 healthy volunteers and 123 subjects with cerebrovascular risk factors and/or ischaemic stroke, who had been studied in our group before. CEC were assessed by immunomagnetic isolation from peripheral blood.

Results In patients with proven and suspected active PCNSV, CEC were extremely elevated (>400 cells/ml in most of the patients) and significantly higher than in healthy and disease controls (p≤0.01 for each group). CEC significantly decreased with immunosuppressive treatment.

Conclusions For the first time it is shown that CEC are significantly elevated in patients with active PCNSV in contrast to other pathologies associated with brain infarction and correlate with disease activity. Sensitivity and specificity of the method for diagnosing PCNSV and the use of the method for treatment monitoring should be addressed in future prospective studies with a larger patient group.

  • Vasculitis
  • Cerebrovascular Disease
  • Stroke

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