Abstract
BackgroundEarlier studies have shown that the absolute number of neutrophil granulocytes (NGs) may increase during attack of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). Whether NGs undergo activation during attack has not yet been investigated. However, as neutrophil elastase (NE) can cleave and inactivate C1-INH which may contribute to the dysregulation of the kallikrein-kinin system and hence, to edema formation. Our aim was to investigate the possible activation of NGs during attacks.MethodsWe studied blood samples obtained from 26 patients with C1-INH-HAE during symptom-free periods and during attacks, along with samples from 26 healthy volunteers. NG count (NGC), NE, myeloperoxidase (MPO), pentraxin 3 (PTX3), CRP, C5a, factor H, IL-8, and TNF-α levels were measured.ResultsNGC was higher during attacks than during symptom-free periods (p = 0.0132), and the same was observed for NE (p = 0.0026), MPO (p = 0.0008), and PTX3 levels (p = 0.0409). There was a strong positive correlation between NE and MPO levels during attacks (p < 0.0001, R = 0.709). Furthermore, IL-8 (p = 0.0061) and TNF-α (p = 0.0186) levels were also elevated during attacks, compared with symptom-free periods. By contrast, C5a and factor H levels were similar in samples obtained during attacks or in symptom-free periods.ConclusionIncreased NGC was associated with elevated NE and MPO levels – this suggests neutrophil activation during attacks. The strong positive correlation between NE and MPO levels, together with the elevated PTX3 concentration, may indicate the expression of neutrophil extracellular traps. All these processes may contribute to the activation of kallikrein-kinin system, which leads to the onset of an edematous episode.
Highlights
Earlier studies have shown that the absolute number of neutrophil granulocytes (NGs) may increase during attack of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE)
Analysis of neutrophil granulocyte counts Because the extravasation of fluid into the extracellular space may result in hemoconcentration of variable extent, we adjusted “during attack” white blood cell (WBC) and NG count (NGC) values with the latter before making comparisons among the study groups
The observed WBC count and NGC measured in during attack samples were divided by the calculated ratio (RBC count during attack/ Red blood cell (RBC) count during symptom-free period) in each patient, to eliminate the changes induced by hemoconcentration
Summary
Earlier studies have shown that the absolute number of neutrophil granulocytes (NGs) may increase during attack of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). Whether NGs undergo activation during attack has not yet been investigated. As neutrophil elastase (NE) can cleave and inactivate C1-INH which may contribute to the dysregulation of the kallikrein-kinin system and to edema formation. Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. It is caused by the reduced antigenic level and/ or functional activity of the C1-inhibitor (C1-INH), resulting from a mutation in the gene encoding C1-INH (SERPING1) [1]. In the deficiency of C1INH, the kallikrein-kinin system undergoes activation and this result in the cleavage of bradykinin from highmolecular-weight kininogen (HK)—a process catalyzed by kallikrein. Acute edema formation in the upper airways may even cause
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