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Low Plasma Gelsolin Concentrations in Chronic Granulomatous Disease

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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, significantly lower pGSN in clinically stable patients with CGD compared with age- and sex-matched healthy volunteers. Low pGSN levels in CGD patients significantly increased following bone marrow transplantation. X-linked carriers of CGD had normal pGSN. In healthy volunteers challenged with intravenous endotoxin, pGSN is not an acute phase reactant.

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Funding

This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

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Authors and Affiliations

  1. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    John Audley, Emily F. Gliniewicz, Kol A. Zarember, Hanna S. Hong, Gal Wald, Elizabeth Kang, Harry L. Malech & John I. Gallin

  2. Neutrophil Monitoring Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    Douglas B. Kuhns

  3. Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Anthony F. Suffredini

  4. Duke Clinical Research Unit, Duke University School of Medicine, Durham, NC, USA

    Robert J. Noveck

  5. BioAegis Therapeutics, Inc., North Brunswick, NJ, USA

    Mark J. Dinubile, Susan L. Levinson & Thomas P. Stossel

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  1. John Audley
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  2. Emily F. Gliniewicz
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  3. Kol A. Zarember
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  7. Elizabeth Kang
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  13. Thomas P. Stossel
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  14. John I. Gallin
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Correspondence to John I. Gallin.

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Conflict of Interest

Susan Levinson and Mark DiNubile are employees of and own stock in BioAegis Therapeutics, Inc. Other authors declare that they have no conflicts of interest.

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All subjects participated following informed consent and were enrolled in IRB-approved clinical protocols in the NIH Clinical Center in accordance with 45 CFR 46.

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Thomas P. Stossel is deceased.

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Audley, J., Gliniewicz, E.F., Zarember, K.A. et al. Low Plasma Gelsolin Concentrations in Chronic Granulomatous Disease. Inflammation 44, 270–277 (2021). https://doi.org/10.1007/s10753-020-01330-w

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  • DOI: https://doi.org/10.1007/s10753-020-01330-w

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