scholarly journals Mechanistic Classification of the Systemic Capillary Leak Syndrome: Clarkson Disease

2014 ◽  
Vol 189 (9) ◽  
pp. 1145-1147 ◽  
Author(s):  
Zhihui Xie ◽  
Chandra C. Ghosh ◽  
Samir M. Parikh ◽  
Kirk M. Druey
Keyword(s):  
Capillary Leak Syndrome ◽  
Capillary Leak ◽  
Systemic Capillary Leak Syndrome ◽  
Clarkson Disease

scholarly journals Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome)

Blood ◽  
2012 ◽  
Vol 119 (18) ◽  
pp. 4321-4332 ◽  
Author(s):  
Zhihui Xie ◽  
Chandra C. Ghosh ◽  
Roshni Patel ◽  
Shoko Iwaki ◽  
Donna Gaskins ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Case Series ◽  
Fiber Formation ◽  
Capillary Leak Syndrome ◽  
Actin Stress Fiber ◽  
Vascular Endothelial ◽  
Capillary Leak ◽  
Systemic Capillary Leak Syndrome ◽  
Humoral Factors ◽  
Clarkson Disease

Abstract The systemic capillary leak syndrome (SCLS) is a rare disorder characterized by transient episodes of hypotensive shock and anasarca thought to arise from reversible microvascular barrier dysfunction. Although the high prevalence of a monoclonal gammopathy of unknown significance in SCLS suggests a pathogenic contribution of endogenous immunoglobulins, the mechanisms of vascular hyperpermeability remain obscure. Herein, we report clinical and molecular findings on 23 patients, the largest SCLS case series to date. Application of episodic SCLS sera, but neither the purified immunoglobulin fraction nor sera obtained from patients during remission, to human microvascular endothelial cells caused vascular endothelial cadherin internalization, disruption of interendothelial junctions, actin stress fiber formation, and increased permeability in complementary functional assays without inducing endothelial apoptosis. Intravenous immunoglobulin, one promising therapy for SCLS, mitigated the permeability effects of episodic sera. Consistent with the presence of endogenous, nonimmunoglobulin, circulating permeability factor(s) constrained to SCLS episodes, we found that vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2), were elevated in episodic SCLS sera but not in remission sera. Ab-based inhibition of Ang2 counteracted permeability induced by episodic SCLS sera. Comparable experiments with anti-VEGF Ab (bevacizumab) yielded less interpretable results, probably because of endothelial toxicity of VEGF withdrawal. Our results support a model of SCLS pathogenesis in which nonimmunoglobulin humoral factors such as VEGF and Ang2 contribute to transient endothelial contraction, suggesting a molecular mechanism for this highly lethal disorder.

scholarly journals Author Correction: A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease)

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Abbas Raza ◽  
Zhihui Xie ◽  
Eunice C. Chan ◽  
Wei-Sheng Chen ◽  
Linda M. Scott ◽  
...  
Keyword(s):  
Mouse Model ◽  
Capillary Leak Syndrome ◽  
Capillary Leak ◽  
Genetic Determinants ◽  
Systemic Capillary Leak Syndrome ◽  
Clarkson Disease

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease)

2018 ◽  
Vol 103 (4) ◽  
pp. 749-759 ◽  
Author(s):  
Zhihui Xie ◽  
Wei‐Sheng Chen ◽  
Yuzhi Yin ◽  
Eunice C. Chan ◽  
Kaoru Terai ◽  
...  
Keyword(s):  
Capillary Leak Syndrome ◽  
Capillary Leak ◽  
Systemic Capillary Leak Syndrome ◽  
Clarkson Disease

scholarly journals Myocardial dysfunction is frequent in systemic capillary-leak syndrome (Clarkson disease) severe episodes

2018 ◽  
Vol 141 (4) ◽  
pp. 1539-1540 ◽  
Author(s):  
Marc Pineton de Chambrun ◽  
Alexis Mathian ◽  
Charles-Edouard Luyt ◽  
Alain Combes ◽  
Zahir Amoura
Keyword(s):  
Myocardial Dysfunction ◽  
Capillary Leak Syndrome ◽  
Capillary Leak ◽  
Systemic Capillary Leak Syndrome ◽  
Clarkson Disease

scholarly journals A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease)

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Abbas Raza ◽  
Zhihui Xie ◽  
Eunice C. Chan ◽  
Wei-Sheng Chen ◽  
Linda M. Scott ◽  
...  
Keyword(s):  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Capillary Leak Syndrome ◽  
Whole Body ◽  
Unknown Etiology ◽  
Capillary Leak ◽  
Systemic Capillary Leak Syndrome ◽  
Genomic Locus ◽  
Peripheral Tissues ◽  
Clarkson Disease

Abstract The systemic capillary leak syndrome (SCLS, Clarkson disease) is a disorder of unknown etiology characterized by recurrent episodes of vascular leakage of proteins and fluids into peripheral tissues, resulting in whole-body edema and hypotensive shock. The pathologic mechanisms and genetic basis for SCLS remain elusive. Here we identify an inbred mouse strain, SJL, which recapitulates cardinal features of SCLS, including susceptibility to histamine- and infection-triggered vascular leak. We named this trait “Histamine hypersensitivity” (Histh/Histh) and mapped it to Chromosome 6. Histh is syntenic to the genomic locus most strongly associated with SCLS in humans (3p25.3), revealing that the predisposition to develop vascular hyperpermeability has a strong genetic component conserved between humans and mice and providing a naturally occurring animal model for SCLS. Genetic analysis of Histh may reveal orthologous candidate genes that contribute not only to SCLS, but also to normal and dysregulated mechanisms underlying vascular barrier function more generally.

scholarly journals Clinical and Pathological Findings of a Fatal Systemic Capillary Leak Syndrome (Clarkson Disease)

Medicine ◽  
2015 ◽  
Vol 94 (9) ◽  
pp. e591 ◽  
Author(s):  
Andrea Zancanaro ◽  
Francesco Serafini ◽  
Giuseppe Fantin ◽  
Bruno Murer ◽  
Marco Cicardi ◽  
...  
Keyword(s):  
Capillary Leak Syndrome ◽  
Pathological Findings ◽  
Capillary Leak ◽  
Systemic Capillary Leak Syndrome ◽  
Clarkson Disease

scholarly journals Neutrophil activation in systemic capillary leak syndrome (Clarkson disease)

2019 ◽  
Vol 23 (8) ◽  
pp. 5119-5127 ◽  
Author(s):  
Zhihui Xie ◽  
Douglas B. Kuhns ◽  
Xuesong Gu ◽  
Hasan H. Otu ◽  
Towia A. Libermann ◽  
...  
Keyword(s):  
Neutrophil Activation ◽  
Capillary Leak Syndrome ◽  
Capillary Leak ◽  
Systemic Capillary Leak Syndrome ◽  
Clarkson Disease
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