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

Nóra Veszeli¹, Dorottya Csuka¹, Zsuzsanna Zotter¹², Éva Imreh³, Mihály Józsi⁴, Szabolcs Benedek⁵, Lilian Varga¹ and Henriette Farkas¹^*

*Corresponding author: Henriette Farkasfarkas.henriette@med.semmelweis-univ.hu

Author Affiliations

¹Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, Budapest, H-1125, Hungary

²Urology Department, Medical Center, Hungarian Defence Forces, Budapest, Hungary

³Central Laboratory, Kútvölgyi Clinical Block, Budapest, Hungary

⁴MTA-ELTE “Lendület” Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary

⁵Haematology Unit, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary

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Orphanet Journal of Rare Diseases 2015, 10:156 doi:10.1186/s13023-015-0374-y

The electronic version of this article is the complete one and can be found online at:http://www.ojrd.com/content/10/1/156

Received:	7 October 2015
Accepted:	2 December 2015
Published:	10 December 2015

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

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.

Keywords:

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