Neutrophil activation during attacks in patients with hereditary angioedema due to C1-inhibitor deficiency

Orphanet Journal of Rare Diseases

Henriette Farkas⁵  Lilian Varga⁵  Szabolcs Benedek³  Mihály Józsi¹  Éva Imreh⁴  Zsuzsanna Zotter²  Dorottya Csuka⁵  Nóra Veszeli⁵ 

[1] MTA-ELTE “Lendület” Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary;Urology Department, Medical Center, Hungarian Defence Forces, Budapest, Hungary;Haematology Unit, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary;Central Laboratory, Kútvölgyi Clinical Block, Budapest, Hungary;Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, Budapest, H-1125, Hungary

关键词: TNF-α;    IL-8;    Myeloperoxidase;    Neutrophil elastase;    Neutrophil activation;    Neutrophil granulocytes;    Edematous attack;    C1-inhibitor deficiency;    Hereditary angioedema;   

Others  :  1235018
DOI  :  10.1186/s13023-015-0374-y

 received in 2015-10-07, accepted in 2015-12-02,  发布年份 2015

【 摘 要 】

Background

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. 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.

Methods

We 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.

Results

NGC 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.

Conclusion

Increased 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.

【 授权许可】

   
2015 Veszeli et al.

【 图 表 】

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