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Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease).

Xie Z, Chan E, Yin Y, Ghosh CC, Wisch L, Nelson C, Young M, Parikh SM, Druey KM - J Clin Cell Immunol (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.

ABSTRACT

Objectives: 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.

No MeSH data available.


Related in: MedlinePlus

Cytokine profiles of SCLS sera. (A–H) Serum cytokines were measured using a Bio-Plex Pro human multiple cytokine assay kit: VEGF (A), CXCL10 (B), CCL2 (C), IL-12 (D), IL-1β (E), IL-6 (F), IL-8 (G) and TNFα (H) (*P < 0.05, **P < 0.01, ****P < 0.00001 Kruskal-Wallis).
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Figure 2: Cytokine profiles of SCLS sera. (A–H) Serum cytokines were measured using a Bio-Plex Pro human multiple cytokine assay kit: VEGF (A), CXCL10 (B), CCL2 (C), IL-12 (D), IL-1β (E), IL-6 (F), IL-8 (G) and TNFα (H) (*P < 0.05, **P < 0.01, ****P < 0.00001 Kruskal-Wallis).

Mentions: Although nearly one quarter of subjects reported flu-like symptoms prior to the onset of a full-blown attack [4], whether this prodrome represents a concomitant infection or is a primary feature of SCLS is unknown. Our previous studies that include a cohort of 23 SCLS subjects demonstrated that some (VEGF, Ang 2), but not all (IL-2), soluble mediators of inflammation were increased in acute SCLS sera [4]. To assess the role of infection and/or inflammation in acute SCLS episodes and to discover new mediators that may contribute to disease onset and/or severity, we analyzed a panel of 27 serum cytokines in sera from 31 SCLS patients in remission, 14 SCLS patients with acute symptoms (samples were not available from all patients), and 37 healthy controls by multiplex bead assay. Ten cytokines (IL-2, IL-4, IL-5, IL-10, IL-13, IL-15, IL-17, G-CSF, GM-CSF, CCL3) were absent or present at very low levels in most sera tested, while levels of the cytokine RANTES were present at levels above the detectable assay range in all samples. Quantities of eight cytokines (IL-1RA, IL-7, IL-9, bFGF, PDGFb, CCL4, and CCL11) did not differ significantly among the groups or between individual SCLS subjects. Consistent with our previous findings, VEGF was increased in acute SCLS sera compared with sera from healthy controls (Figure 2A). We detected significantly increased levels of seven cytokines in acute SCLS sera relative to sera from healthy donors, specifically, CXCL10, CCL2, IL-12, IL-1β, IL-6, IL-8, and TNFα (Figures 2B–2H). Of all cytokines measured, only CXCL10 was significantly increased both in baseline and acute SCLS sera relative to controls (Figure 2B). These data suggested that TH1-associated inflammation or infection is associated with acute SCLS episodes.


Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease).

Xie Z, Chan E, Yin Y, Ghosh CC, Wisch L, Nelson C, Young M, Parikh SM, Druey KM - J Clin Cell Immunol (2014)

Cytokine profiles of SCLS sera. (A–H) Serum cytokines were measured using a Bio-Plex Pro human multiple cytokine assay kit: VEGF (A), CXCL10 (B), CCL2 (C), IL-12 (D), IL-1β (E), IL-6 (F), IL-8 (G) and TNFα (H) (*P < 0.05, **P < 0.01, ****P < 0.00001 Kruskal-Wallis).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232957&req=5

Figure 2: Cytokine profiles of SCLS sera. (A–H) Serum cytokines were measured using a Bio-Plex Pro human multiple cytokine assay kit: VEGF (A), CXCL10 (B), CCL2 (C), IL-12 (D), IL-1β (E), IL-6 (F), IL-8 (G) and TNFα (H) (*P < 0.05, **P < 0.01, ****P < 0.00001 Kruskal-Wallis).
Mentions: Although nearly one quarter of subjects reported flu-like symptoms prior to the onset of a full-blown attack [4], whether this prodrome represents a concomitant infection or is a primary feature of SCLS is unknown. Our previous studies that include a cohort of 23 SCLS subjects demonstrated that some (VEGF, Ang 2), but not all (IL-2), soluble mediators of inflammation were increased in acute SCLS sera [4]. To assess the role of infection and/or inflammation in acute SCLS episodes and to discover new mediators that may contribute to disease onset and/or severity, we analyzed a panel of 27 serum cytokines in sera from 31 SCLS patients in remission, 14 SCLS patients with acute symptoms (samples were not available from all patients), and 37 healthy controls by multiplex bead assay. Ten cytokines (IL-2, IL-4, IL-5, IL-10, IL-13, IL-15, IL-17, G-CSF, GM-CSF, CCL3) were absent or present at very low levels in most sera tested, while levels of the cytokine RANTES were present at levels above the detectable assay range in all samples. Quantities of eight cytokines (IL-1RA, IL-7, IL-9, bFGF, PDGFb, CCL4, and CCL11) did not differ significantly among the groups or between individual SCLS subjects. Consistent with our previous findings, VEGF was increased in acute SCLS sera compared with sera from healthy controls (Figure 2A). We detected significantly increased levels of seven cytokines in acute SCLS sera relative to sera from healthy donors, specifically, CXCL10, CCL2, IL-12, IL-1β, IL-6, IL-8, and TNFα (Figures 2B–2H). Of all cytokines measured, only CXCL10 was significantly increased both in baseline and acute SCLS sera relative to controls (Figure 2B). These data suggested that TH1-associated inflammation or infection is associated with acute SCLS episodes.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Allergic Diseases, NIAID/NIH, Bethesda, MD, USA.

ABSTRACT

Objectives: 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.

No MeSH data available.


Related in: MedlinePlus