Intravenous Immunoglobulins Tapering and Withdrawal in Systemic Capillary Leak Syndrome (Clarkson Disease)

Moyon, Quentin; Chambrun, Marc Pineton de; Gousseff, Marie; Hié, M.; Urbanski, G.; Verlicchi, Franco; Faguer, Stanislas; Dossier, Antoine; Lega, Jean‐Christophe; Rivière, Sophie; Saadoun, David; Graveleau, J.; Lucchini-Lecomte, Marie-Josée; Christides, C.; Moal, S. Le; Bibes, B.; Malizia, Giuseppe; Ruivard, M.; Blaison, G.; Alric, Laurent; Agard, C.; Soubrier, Martin; Viallard, Jean‐François; Lévesque, H.; Rivard, Georges‐Étienne; Tieulié, N.; Hot, A.; Lovey, Pierre‐Yves; Hanslik, Thomas; Lhote, F.; Eble, Vincent; Troncoso, Jorge Álvarez; Aujayeb, Avinash; Quentric, Paul; Taieb, Dov; Cohen‐Aubart, Fleur; Lambert, Marc; Amoura, Zahir

doi:10.1016/j.jaip.2022.07.006

Cited by 6 publications

(2 citation statements)

References 16 publications

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“…Mortality during ISCLS flares approaches 30%, in part because no acute intervention has been proven to shorten the duration of episodes or prevent complications ( 1 ). By contrast, monthly prophylaxis with high-dose intravenous immunoglobulins (IVIGs) substantially reduces the frequency and severity of ISCLS flares and increases survival ( 3 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

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Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease

Ablooglu,

Chen,

Xie

et al. 2024

Journal of Clinical Investigation

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Clarkson disease, or monoclonal gammopathy–associated idiopathic systemic capillary leak syndrome (ISCLS), is a rare, relapsing-remitting disorder featuring the abrupt extravasation of fluids and proteins into peripheral tissues, which in turn leads to hypotensive shock, severe hemoconcentration, and hypoalbuminemia. The specific leakage factor(s) and pathways in ISCLS are unknown, and there is no effective treatment for acute flares. Here, we characterize an autonomous vascular endothelial defect in ISCLS that was recapitulated in patient-derived endothelial cells (ECs) in culture and in a mouse model of disease. ISCLS-derived ECs were functionally hyperresponsive to permeability-inducing factors like VEGF and histamine, in part due to increased endothelial nitric oxide synthase (eNOS) activity. eNOS blockade by administration of N (γ)-nitro- l -arginine methyl ester ( l -NAME) ameliorated vascular leakage in an SJL/J mouse model of ISCLS induced by histamine or VEGF challenge. eNOS mislocalization and decreased protein phosphatase 2A (PP2A) expression may contribute to eNOS hyperactivation in ISCLS-derived ECs. Our findings provide mechanistic insights into microvascular barrier dysfunction in ISCLS and highlight a potential therapeutic approach.

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Section: Introductionmentioning

confidence: 99%

“…However, extensive proteomics profiling of acute ISCLS sera has not yet uncovered unique humoral factor(s) that may trigger attacks ( 7 , 8 ). More than 90% of patients with ISCLS have a monoclonal gammopathy of unknown significance (MGUS, typically IgG κ), but its role in disease pathogenesis is unknown ( 5 ).…”

Section: Introductionmentioning

confidence: 99%