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

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 (TNF alpha) 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 TNF alpha 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 mu g/ml (224-285) vs. 293 mu g/ml (263-329), (median (25-75% percentiles, p = 0.035) and TNF alpha 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) mu g/ml to 287 (261-317) mu g/ml (p = 0.021). TNF alpha and CRP levels did not change significantly. We found no significant correlation among fetuin-A CRP, TNF alpha 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.