Systemic Redox Imbalance in Patients with Chronic Granulomatous Disease.

Edyta Heropolitanska-Pliszka,Joanna Karpinska,Aleksandra Lewandowicz-Uszynska,Anna Zalewska,Klaudia Berk,Jolanta Sawicka-Powierza,Nel Dabrowska-Leonik,Beata Wolska-Kusnierz,Ewa Bernatowska,Barbara Piatosa,Bozena Mikoluc,Mateusz Maciejczyk,Malgorzata Pac

doi:10.3390/jcm9051397

Abstract

The aim of our study was to evaluate redox status, enzymatic and non-enzymatic antioxidant barriers, oxidative damage of proteins, lipids and DNA, as well as concentration of coenzyme Q10 and vitamins A and E in patients with chronic granulomatous disease (CGD). The study was performed on fifteen Caucasian individuals (median age 24 years and seven months) diagnosed with CGD. The mutation in the NCF1 gene was confirmed in ten patients, and in the CYBB gene in five patients. We demonstrated high levels of total oxidant status (TOS) and oxidative stress index (OSI), lipids (↑8-isoprostanes (8-isoP), ↑4-hydroxynonenal (4-HNE)), proteins (↑advanced oxidation protein products (AOPP)) and DNA (↑8-hydroxy-2’-deoxyguanosine (8-OHdG)) oxidation products in CGD individuals as compared to sex- and age-matched healthy controls. We showed enhanced serum enzymatic activity of catalase (CAT) and superoxide dismutase-1 (SOD) and significantly decreased coenzyme Q10 concentration. Our study confirmed redox disturbances and increased oxidative damage in CGD patients, and indicated the need to compare redox imbalance depending on the type of mutation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The question regarding effectiveness of antioxidant therapy in patients with CGD is open, and the need to establish guidelines in this area remains to be addressed.

Highlights

IntroductionChronic granulomatous disease (CGD) is a rare (one in 200,000–250,000 live births), hereditary, primary immunodeficiency disorder (PID) [1]
Chronic granulomatous disease (CGD) is a rare, hereditary, primary immunodeficiency disorder (PID) [1]
Our data indicate that unfavorable oxidant/antioxidant balance is a feature of chronic granulomatous disease, caused by a predisposition to develop a hyperinflammatory state due to various disturbances of the innate immune response

Summary

Introduction

Chronic granulomatous disease (CGD) is a rare (one in 200,000–250,000 live births), hereditary, primary immunodeficiency disorder (PID) [1]. The hallmark of CGD is impairment in superoxide production caused by mutation of one of six genes that encode proteins in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex (NOX2) present mainly in professional phagocytes [2]. Other symptoms include a variety of inflammatory conditions unrelated to infections such as granuloma formation, colitis and increased frequency of autoimmune diseases [5]. Despite the proinflammatory nature of immune cells previously reported in CGD patients, redox homeostasis has not yet been evaluated in this group of patients. The aim of our study was to assess redox status, enzymatic and non-enzymatic antioxidant barriers, oxidative damage to proteins, lipids and DNA, as well as levels of coenzyme Q10 and vitamins A and E in patients with CGD in comparison to healthy controls

Objectives

Methods

Conclusion