Low Plasma Gelsolin Concentrations in Chronic Granulomatous Disease
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ORIGINAL ARTICLE
Low Plasma Gelsolin Concentrations in Chronic Granulomatous Disease John Audley,1 Emily F. Gliniewicz,1 Kol A. Zarember,1 Hanna S. Hong,1 Gal Wald,1 Douglas B. Kuhns,2 Elizabeth Kang,1 Harry L. Malech,1 Anthony F. Suffredini,3 Robert J. Noveck,4 Mark J. Dinubile,5 Susan L. Levinson,5 Thomas P. Stossel,5 and John I. Gallin 1,6 Received 18 June 2020; accepted 20 August 2020
Abstract— Plasma gelsolin (pGSN) is the secreted isoform of an intracellular actin remodeling
protein found in high concentrations in human plasma. Clinical studies demonstrate reduced pGSN concentrations in several disease states, including severe trauma, burns, and sepsis. Markedly decreased pGSN concentrations in these conditions precede and predict adverse clinical outcomes. In this study, we measured pGSN in patients with chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent infections and dysregulated inflammation. pGSN was quantified using a sandwich ELISA in plasma from healthy volunteers, clinically stable CGD patients, and X-linked CGD carriers and in sera from 12 CGD patients undergoing bone marrow transplantation. pGSN was also quantified in healthy volunteers challenged with intravenous endotoxin. pGSN concentrations were lower in CGD patients without active infection or systemic inflammation compared with healthy control subjects. In CGD patients undergoing bone marrow transplantation, pGSN concentrations increased significantly following successful transplant. X-linked carriers of CGD had normal pGSN. Despite reduction of pGSN in CGD patients, we did not detect significant changes in pGSN over 24 h following challenge of healthy volunteers with intravenous endotoxin (4 ng/kg) that elicited a febrile response. We describe, for the first time,
Thomas P. Stossel is deceased. 1
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 2 Neutrophil Monitoring Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA 3 Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA 4 Duke Clinical Research Unit, Duke University School of Medicine, Durham, NC, USA 5 BioAegis Therapeutics, Inc., North Brunswick, NJ, USA 6 To whom correspondence should be addressed at Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Email: [email protected]
0360-3997/20/0000-0001/0 # 2020 This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply
Audley, Gliniewicz, Zarember, Hong, Wald, Kuhns, Kang, Malech, Suffredini, Noveck, Dinubile, Levinson, Stossel, and Gallin
significantly lower pGSN in clinically stable patients with CGD compared with age- and sexmatched healthy volunteers. Low pGSN levels in CGD patients significantly increased following bone marrow transplantation. X-linked
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