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Pathogenic studies of Systemic Capillary Leak Syndrome

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NIAID

CLIN-32

Authors

  • Z. Xie
  • C.C. Ghost
  • K. Terai
  • S. Iwaki
  • A. Sek
  • R. Patel
  • C. Nelson
  • L. Wisch
  • M. Young
  • A.Z. Dudek
  • P.R. Greipp
  • S.M. Parikh
  • K.M. Druey

Abstract

The systemic capillary leak syndrome (SCLS) is an extremely rare disorder characterized by transient but reversible episodes of hypotensive shock and massive vascular leakage. Fewer than 200 cases have been reported since discovered in 1960. Using samples from a cohort of > 30 patients, we reported previously that episodic serum induced vascular hyperpermeability and disruption of endothelial adherens junctions. We present here that Blood Outgrowth Endothelial Cells (BOEC) from SCLS patients exhibit differential gene expression patterns. VEGF and endothelin receptor A was upregulated in BOEC derived from SCLS subjects. Serum inflammatory cytokines, including CXCL10, IL-6 and VEGF, were significantly elevated during acute attacks. Although the trigger for acute SCLS episodes is unknown, there is evidence of phenotypic diversity within the cohort. Serum from a unique patient who experiences regularly timed, mild, stereotyped episodes contained high levels of permeability mediators TNF╬▒ and IL-8. Acute serum from this subject induced endothelial surface marker activation and hyperpermeability in vitro, which was sensitive to blockade of either factor. In conclusion, our data suggest that endothelial cells from subjects with SCLS may have intrinsic gene expression abnormalities, when combined with acute deflections in serum factors during acute attack, could induce vascular hyperpemeability and clinical symptoms.

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