title: Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease).
abstract: OBJECTIVE
  The Systemic Capillary Leak Syndrome (SCLS) is a rare and potentially fatal disorder resembling systemic anaphylaxis that is characterized by transient episodes of hypotensive shock and peripheral edema. The pathogenesis of SCLS is unknown, and triggers for attacks are apparent only in a minority of patients. We introduce a clinical algorithm for the diagnosis of SCLS, and we investigated potential serum biomarkers of acute SCLS episodes.
  
  
  METHODS
  We analyzed serum cytokines in a cohort of 35 patients with an established diagnosis of SCLS and characterized the effects of SCLS sera on endothelial cell function. We investigated the cellular source(s) of CXCL10, a chemokine that was significantly elevated in both basal and acute SCLS sera, by flow cytometry.
  
  
  RESULTS
  Several cytokines were elevated in acute SCLS sera compared to baseline or sera from healthy controls, including CXCL10, CCL2, IL-1β, IL-6, IL-8, IL-12 and TNFα. The majority of acute sera failed to activate endothelial cells as assessed by surface adhesion marker expression. Monocytes appear to be the major source of serum CXCL10, and the percentage of CXLC10+ monocytes in response to IFNγ stimulation was increased in SCLS subjects compared to controls.
  
  
  CONCLUSIONS
  The presence of proinflammatory cytokines in acute SCLS sera suggests that inflammation or infection may have a role in triggering episodes. The enhanced capacity of monocytes from SCLS patients to produce CXCL10 suggests a new therapeutic avenue for SCLS.
authors.affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Eunice
authors.initials: E
authors.lastname: Chan
authors.affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Chandra C
authors.initials: CC
authors.lastname: Ghosh
authors.affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Wisch
authors.affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Celeste
authors.initials: C
authors.lastname: Nelson
authors.affiliation: Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Young
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Samir M
authors.initials: SM
authors.lastname: Parikh
authors.affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Druey
keywords: CXCL10; Cytokines; Inflammation; Monocytes; Systemic capillary leak syndrome