Low Plasma Gelsolin Concentrations in Chronic Granulomatous Disease.
John AudleyEmily F GliniewiczKol A ZaremberHanna S HongGal WaldDouglas B KuhnsElizabeth KangHarry L MalechAnthony F SuffrediniRobert J NoveckMark J DinubileSusan L LevinsonThomas P StosselJohn I GallinPublished in: Inflammation (2020)
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.
Keyphrases
- end stage renal disease
- bone marrow
- patients undergoing
- ejection fraction
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- mesenchymal stem cells
- prognostic factors
- oxidative stress
- acute kidney injury
- emergency department
- intensive care unit
- systemic sclerosis
- cell therapy
- low dose
- rheumatoid arthritis
- reactive oxygen species
- early onset