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Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period

T. Grymova, M. Vlkova, P. Soucek, R. Hakl, J. Nechvatalova, P. Slanina, J. Stichova, J. Litzman, T. Freiberger,

. 2019 ; 2019 (-) : 9515628. [pub] 20190519

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc20006217

Grant support
NV15-28732A MZ0 CEP Register

Neutrophils impact on processes preceding the formation of bradykinin, a major swelling mediator in hereditary angioedema (HAE), yet their potential role in HAE pathogenesis has not been sufficiently studied. We assessed the relative mRNA expression of 10 genes related to neutrophil activation using RNA extracted from the peripheral blood neutrophils of 23 HAE patients in a symptom-free period and 39 healthy donors. Increased relative mRNA expression levels of CD274, IL1B, IL1RN, IL8, MMP9, and TLR4, together with a lack in their mutual correlations detected in HAE patients compared to healthy controls, suggested a preactivated state and dysregulation of patients' neutrophils. Patients' neutrophil-alerted state was further supported by increased CD11b, decreased CD16 plasma membrane deposition, and increased relative CD274+ and CD87+ neutrophil counts, but not by increased neutrophil elastase or myeloperoxidase plasma levels. As CD274 mediates inhibitory signals to different immune cells, neutrophils were cocultured with T-cells/PBMC. The decrease in CD25+ and IFN-γ+ T-cell/PBMC ratio in patients indicated the patients' neutrophil suppressive functions. In summary, the results showed neutrophils' alerted state and dysregulation at the transcript level in patients with HAE types I and II even in a symptom-free period, which might make them more susceptible to edema formation. Neutrophils' T-cell suppressive capacity in HAE patients needs to be further investigated.

References provided by Crossref.org

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$a Neutrophils impact on processes preceding the formation of bradykinin, a major swelling mediator in hereditary angioedema (HAE), yet their potential role in HAE pathogenesis has not been sufficiently studied. We assessed the relative mRNA expression of 10 genes related to neutrophil activation using RNA extracted from the peripheral blood neutrophils of 23 HAE patients in a symptom-free period and 39 healthy donors. Increased relative mRNA expression levels of CD274, IL1B, IL1RN, IL8, MMP9, and TLR4, together with a lack in their mutual correlations detected in HAE patients compared to healthy controls, suggested a preactivated state and dysregulation of patients' neutrophils. Patients' neutrophil-alerted state was further supported by increased CD11b, decreased CD16 plasma membrane deposition, and increased relative CD274+ and CD87+ neutrophil counts, but not by increased neutrophil elastase or myeloperoxidase plasma levels. As CD274 mediates inhibitory signals to different immune cells, neutrophils were cocultured with T-cells/PBMC. The decrease in CD25+ and IFN-γ+ T-cell/PBMC ratio in patients indicated the patients' neutrophil suppressive functions. In summary, the results showed neutrophils' alerted state and dysregulation at the transcript level in patients with HAE types I and II even in a symptom-free period, which might make them more susceptible to edema formation. Neutrophils' T-cell suppressive capacity in HAE patients needs to be further investigated.
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$a Vlkova, Marcela $u Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. St. Anne's University Hospital, Brno, Czech Republic.
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$a Soucek, Premysl $u Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic. Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.
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$a Hakl, Roman $u Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. St. Anne's University Hospital, Brno, Czech Republic.
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$a Slanina, Peter $u Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. St. Anne's University Hospital, Brno, Czech Republic.
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$a Stichova, Julie $u Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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$a Freiberger, Tomas $u Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic. Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.
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