Elevated Concentration of Defensins in Hepatitis C Virus-Infected Patients

Abstract

Hepatitis C virus (HCV) is the major etiological agent of human non-A and non-B hepatitis, affecting around 180 million people worldwide. Defensins, small cysteine-rich cationic peptides, are shown to have potent antibacterial, antiviral, and antifungal properties. Defensins can be found in both normal and microbial infected patients, at variable concentrations. Notably, viral infections are often associated with elevated concentrations of defensins. The current study aimed to estimate the concentrations of total, α-, and β-defensins in serum taken from normal and HCV-infected patients. 12 healthy (noninfected) and 34 HCV-infected patients were enrolled. Standardized immunoassay kits were used to obtain serum concentrations of defensins. The obtained results were calibrated against kit standard reagents. Total defensin concentrations in HCV-infected patients were significantly higher (2- to 105-fold) compared to healthy individuals. The concentrations of α-defensins were also significantly elevated in the HCV-infected patients (31–1398 ng/50 μL). However, concentrations of β-defensins ranged from 44.5 ng/50 μL to 1056 ng/50 μL. The results did not reveal differences in serum defensin concentration between male and female HCV-infected patients. A-defensin concentration of ≥250 ng/50 μL was found to contain more β-defensins than total defensins and α-defensins. This study concludes, for the first time, that serum defensin levels are elevated in HCV-infected patients.

Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

“…Some of these values fall within the range of concentrations of said peptides in different body fluids of healthy individuals reported in literature. It is mostly true for LL-37, which was detected in concentration of 0.15–6.1 μM in saliva, of 0.16–1.9 μM in bronchoalveolar lavage (BAL), and of 0.2–0.5 μM in plasma (Byfield et al, 2011), and to the lesser extent for α-defencin, which was found in plasma in concentration of around 80–95 nM [13.5 ± 1.2 ng/50 μL according to Mattar et al (2016) and 323.3 ± 173.1 ng/ml according to Mukae et al (2002)] and in BAL in concentration of 3.7 nM (12.9 ± 15) ng/ml according to Mukae et al (2002). However, for β-defensins reported concentrations were lower, in saliva their detected levels were 2.2 (0.3–4.8) nM [9.5 (1.2–21) μg/L] for hBD-2 and 63 (10–182) nM [326 (50–931) μg/L] for hBD-3 (Ghosh et al, 2007), hBD-2 concentration in serum was reported to be only 8.3 ± 3.9 pM (36.1 ± 17.0 pg/ml) (Arimura et al, 2004), and hBD-3 was not detected in BAL (Ghosh et al, 2007).…”

Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes

“…Its expression could be then induced as early as 3 h postinfection with IAV, Sendai virus or, in a much lesser extent, HSV-1 (Ryan et al, 2011). Finally, hBD concentrations have been demonstrated to be elevated after exposure to Hepatitis B (HBV) and C (HCV) viruses as well as to Crimean-Congo hemorrhagic fever virus (CCHFV) (Bai et al, 2015;Aksoy et al, 2016;Mattar et al, 2016a). Concentrations of hBDs were shown to be significantly higher in HCV-infected patient sera, ranging from 900 to 21,120 ng/mL, compared to controls where they were less than 60 ng/mL (Mattar et al, 2016a).…”

“…Finally, hBD concentrations have been demonstrated to be elevated after exposure to Hepatitis B (HBV) and C (HCV) viruses as well as to Crimean-Congo hemorrhagic fever virus (CCHFV) (Bai et al, 2015;Aksoy et al, 2016;Mattar et al, 2016a). Concentrations of hBDs were shown to be significantly higher in HCV-infected patient sera, ranging from 900 to 21,120 ng/mL, compared to controls where they were less than 60 ng/mL (Mattar et al, 2016a). In the same way, serum hBD2 levels were significantly increased in patients infected with CCHFV compared to healthy controls and were three-times higher in patients with non-fatal evolution of the disease than in patients with fatal disease (89,480 vs. 30,580 ng/mL) suggesting a protective role of the peptide during the infection (Aksoy et al, 2016).…”

Association between Immunologic Markers and Cirrhosis in Individuals from a Prospective Chronic Hepatitis C Cohort

“…DEFA-1 appeared as a biomarker in the immune response pathway analysis. At least two studies have implicated HNPs 1-4 in the progression of liver fibrosis in patients with chronic hepatitis C [ 37 , 38 ]. The likely mechanism of action involves stimulation of liver HSCs and Kupffer cells, which under the influence of DEFA-1 release pro-inflammatory cytokines, IL-8 and TNF-alpha, contribute to the maintenance of inflammation [ 2 , 39 , 40 ].…”