Upregulation of cytokines and IL-17 in patients with hereditary angioedema

Arcoleo, Francesco; Salemi, Marilisa; Porta, Antonio La; Selvaggio, Valentina; Mandalà, V.; Muggeo, Vito M. R.; Misiano, Gabriella; Milano, Salvatore; Romano, Giuseppina Colonna; Cillari, Enrìco

doi:10.1515/cclm-2013-1008

Cited by 12 publications

(14 citation statements)

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“…Changes in neutrophil activation markers were detected mostly during HAE attacks in previous studies [17, 24, 25]. Regarding symptom-free periods, only single cytokines related to neutrophil activation (IL-8, IL-17) have been described as upregulated in individual patients so far [24, 26].…”

Section: Discussionmentioning

confidence: 97%

“…Neutrophils are known to have the potential to influence several processes preceding the formation of bradykinin, a major mediator of swelling in HAE. To date, however, only a limited number of studies have pointed to the role of neutrophil activation in HAE, all of them addressing markers in serum or plasma [15, 22–24]. Changes in neutrophil activation markers were detected mostly during HAE attacks in previous studies [17, 24, 25].…”

Section: Discussionmentioning

confidence: 99%

“…To date, however, only a limited number of studies have pointed to the role of neutrophil activation in HAE, all of them addressing markers in serum or plasma [15, 22–24]. Changes in neutrophil activation markers were detected mostly during HAE attacks in previous studies [17, 24, 25]. Regarding symptom-free periods, only single cytokines related to neutrophil activation (IL-8, IL-17) have been described as upregulated in individual patients so far [24, 26].…”

Section: Discussionmentioning

confidence: 99%

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

Grymova

Vlková

Souček

et al. 2019

Mediators of Inflammation

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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 ofCD274,IL1B,IL1RN,IL8,MMP9, andTLR4, 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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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Grymova

Vlková

Souček

et al. 2019

Mediators of Inflammation

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“…A recent study with 17 HAE patients showed that various cytokine levels increase during an HAE attack. Interestingly, IL-17 was also elevated in the absence of symptoms [30]. This cytokine stimulates CRP expression in hepatocytes and smooth muscle cells [31].…”

Section: Discussionmentioning

confidence: 98%

C-reactive protein levels in hereditary angioedema

Hofman

Relan

Hack

2014

Clinical and Experimental Immunology

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SummaryHereditary angioedema (HAE) patients experience recurrent episodes of angioedema attacks that can be painful, disfiguring and even life-threatening. The disorder results from a mutation in the gene that controls the synthesis of C1-inhibitor (C1INH). C1INH is a major regulator of activation of the contact system. It is often assumed that attacks results from uncontrolled local activation of the contact system with subsequent formation of bradykinin. To evaluate the involvement of inflammatory reactions in HAE, we analysed C-reactive protein (CRP) levels. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. For the current study we analysed CRP levels when patients were asymptomatic, during a clinical attack and in a follow-up period, and correlated these with the clinical manifestations of the attack. Data from 68 HAE patients were analysed and included CRP levels on 273 occasions. While asymptomatic, 20% of the patients analysed had increased CRP. At the onset of the attack (P = 0·049) and during the next 24 h CRP rose significantly (P = 0·002) in patients with an abdominal location, and post-attack levels were significantly higher in these patients than in patients with attacks at other locations (P = 0·034). In conclusion, CRP levels are elevated in a substantial proportion of asymptomatic HAE patients. Levels of CRP increase significantly during an abdominal attack. These data suggest low-grade systemic inflammatory reactions in HAE patients as well as a triggering event for attacks that starts prior to symptom onset.

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“…Only limited data have been published on the role of cytokines in C1-INH-HAE, and even these are available from a small number of cases. Most of these studies did not compare samples obtained from the same patients during and between edematous attacks, and all analyzed serum samples [ 24 – 26 ]. Serum is the least suitable sample type for measuring cytokine levels.…”

Section: Discussionmentioning

confidence: 99%

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

Veszeli

Csuka

Zotter

et al. 2015

Orphanet J Rare Dis

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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.

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Upregulation of cytokines and IL-17 in patients with hereditary angioedema

Cited by 12 publications

References 1 publication

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

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

C-reactive protein levels in hereditary angioedema

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

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