Serum fetuin-A, tumor necrosis factor alpha and C-reactive protein concentrations in patients with hereditary angioedema with C1-inhibitor deficiency

Bernadett Márkus; Nóra Veszeli; György Temesszentandrási; Henriette Farkas; László Kalabay

doi:10.1186/s13023-019-0995-7

Serum fetuin-A, tumor necrosis factor alpha and C-reactive protein concentrations in patients with hereditary angioedema with C1-inhibitor deficiency

Orphanet J Rare Dis. 2019 Mar 18;14(1):67. doi: 10.1186/s13023-019-0995-7.

Authors

Bernadett Márkus¹, Nóra Veszeli², György Temesszentandrási², Henriette Farkas², László Kalabay^{3

4}

Affiliations

¹ Department of Family Medicine, Semmelweis University, Budapest POB 2, Kútvölgyi str. 4, Budapest, H-1125, Hungary.
² Hungarian Angioedema Reference Center, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
³ Department of Family Medicine, Semmelweis University, Budapest POB 2, Kútvölgyi str. 4, Budapest, H-1125, Hungary. laszlo.kalabay@med.semmelweis-univ.hu.
⁴ Semmelweis University, POB 2, Budapest, H-1428, Hungary. laszlo.kalabay@med.semmelweis-univ.hu.

Abstract

Background and aims: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by localized, non-pitting, and transient swelling of submucosal or subcutaneous region. Human fetuin-A is a multifunctional glycoprotein that belongs to the proteinase inhibitor cystatin superfamily and has structural similarities to the high molecular weight kininogen. Fetuin-A is also known a negative acute phase reactant with anti-inflammatory characteristics. In this study we aimed to determine serum fetuin-A, C-reactive protein (CRP) and tumor necrosis factor alpha (TNFα) concentrations in patients with C1-INH-HAE during symptom-free period and during attacks and compare them to those of healthy controls. Further we analyzed possible relationship among these parameters as well as D-dimer levels which was known as marker of HAE attacks.

Patients and methods: Serum samples of 25 C1-INH-HAE patients (8 men, 17 women, age: 33.1 ± 6.9 years, mean ± SD) were compared to 25 healthy controls (15 men, 10 women, age: 32.5 ± 7.8 years). Serum fetuin-A and TNFα concentrations were determined by ELISA, CRP and D-dimer by turbidimetry.

Results: Compared to healthy controls patients with C1-INH-HAE in the symptom-free period had significantly decreased serum fetuin-A 258 μg/ml (224-285) vs. 293 μg/ml (263-329), (median (25-75% percentiles, p = 0.035) and TNFα 2.53 ng/ml (1.70-2.83) vs. 3.47 ng/ml (2.92-4.18, p = 0.0008) concentrations. During HAE attacks fetuin-A levels increased from 258 (224-285) μg/ml to 287 (261-317) μg/ml (p = 0.021). TNFα and CRP levels did not change significantly. We found no significant correlation among fetuin-A CRP, TNFα and D-dimer levels in any of these three groups.

Conclusions: Patients with C1-INH-HAE have decreased serum fetuin-A concentrations during the symptom-free period. Given the anti-inflammatory properties of fetuin-A, the increase of its levels may contribute to the counter-regulation of edema formation during C1-INH-HAE attacks.

Keywords: C-reactive protein; C1 inhibitor deficiency; Fetuin-A; Hereditary angioedema; Tumor necrosis factor alpha.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Angioedemas, Hereditary / blood*
Angioedemas, Hereditary / physiopathology*
Blood Chemical Analysis
C-Reactive Protein / metabolism*
Female
Humans
Male
Tumor Necrosis Factor-alpha / blood
alpha-2-HS-Glycoprotein / metabolism*

Substances

Tumor Necrosis Factor-alpha
alpha-2-HS-Glycoprotein
C-Reactive Protein