Neutrophil activation in systemic capillary leak syndrome (Clarkson disease)

Authors

Zhihui Xie, NIAID/NIH
Douglas B. Kuhns, NCI/NIH
Xuesong Gu, Beth Israel Deaconess Medical Center & Harvard Medical School
Hasan H. Otu, University of Nebraska-LincolnFollow
Towia A. Libermann, Beth Israel Deaconess Medical Center & Harvard Medical School
John I. Gallin, NIAID/NIH
Samir M. Parikh, Beth Israel Deaconess Medical Center & Harvard Medical School
Kirk M. Druey, NIAID/NIHFollow

ORCID IDs

Kirk M. Druey

Document Type

Article

Date of this Version

2019

Citation

J Cell Mol Med. 2019;23:5119–5127

Comments

© 2019 The Authors.

Open access

DOI: 10.1111/jcmm.14381

Abstract

Systemic capillary leak syndrome (SCLS; Clarkson disease) is a rare orphan disorder characterized by transient yet recurrent episodes of hypotension and peripheral oedema due to diffuse vascular leakage of fluids and proteins into soft tissues. Humoral mediators, cellular responses and genetic features accounting for the clinical phenotype of SCLS are virtually unknown. Here, we searched for factors altered in acute SCLS plasma relative to matched convalescent samples using multiplexed aptamer‐based proteomic screening. Relative amounts of 612 proteins were changed greater than twofold and 81 proteins were changed at least threefold. Among the most enriched proteins in acute SCLS plasma were neutrophil granule components including bactericidal permeability inducing protein, myeloperoxidase and matrix metalloproteinase 8. Neutrophils isolated from blood of subjects with SCLS or healthy controls responded similarly to routine pro‐inflammatory mediators. However, acute SCLS sera activated neutrophils relative to remission sera. Activated neutrophil supernatants increased permeability of endothelial cells from both controls and SCLS subjects equivalently. Our results suggest systemic neutrophil degranulation during SCLS acute flares, which may contribute to the clinical manifestations of acute vascular leak.