Decreased redox state in red blood cells from patients with sarcoidosis

BACKGROUND AND AIM OF THE WORK: The glutathione system has a key role in the defence against oxidative stress. To function properly, this system needs NADPH to maintain glutathione (GSH) in its reduced form. We hypothesized that the clinical problems associated with sarcoidosis might be related to a decreased anti-oxidant defence and we therefore measured the activity of the NADPH-generating enzyme glucose-6-phosphate dehydrogenase (G6PD), the GSH-regenerating enzyme glutathione reductase (GR) and indirectly the level of NADPH in red blood cells from patients with sarcoidosis. METHODS: In a population of sarcoidosis (n = 88) patients, G6PD, GR and GR activity after incubation with chromate (GR-Cr) were measured in erythrocytes. A decreased concentration of NADPH was revealed by an increased GR-Cr (> 0.6 IU/g Hb). To exclude a mutation in the G6PD gene, sequencing was performed in cases with an abnormal GR-Cr. Sarcoidosis pulmonary disease severity was evaluated by means of laboratory data, radiographic staging, HRCT scoring, pulmonary function and exercise capacity testing. RESULTS: Fourteen (29.2%) females and one (2.5%) male demonstrated an increased GR-Cr test, indicative of a decreased NADPH level. Patients with an abnormal test result demonstrated also significantly increased ACE and GR values (p < 0.05). Only one female case (of 6 tested) appeared to have a mutation in the G6PD gene. CONCLUSION: In a considerable percentage of female patients with sarcoidosis, a decreased level of NADPH in the erythrocytes was found.