BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency (PID) caused by a dysfunctional respiratory burst enzyme NADPH-oxidase. The concurrence of Klinefelter’s Syndrome (KS) and CGD would be extremely rare.
OBJECTIVE: We describe the study of a family where the youngest male child had X-linked CGD (X-CGD) while his older brother was both an X-CGD carrier and a Klinefelter.
METHODS: Flow cytometry was used to study respiratory burst and gp91-phox expression, while genetic investigation was done by RT-PCR, PCR and X-chromosome short tandem repeat (X-STR) analysis.
RESULTS: The Dihydrorhodamine (DHR) assay showed the patient’s neutrophils failed to produce a respiratory burst, while both the mother and an older brother showed a bimodal response. gp91-phox expression was absent in the patient’s neutrophils, and bimodal in the mother’s and brother’s neutrophils. The patient’s cDNA showed a C>T change at nucleotide 676 of the CYBB gene. The same change was seen in the patient’s gDNA, while the brother and mother were heterozygous, with C and T, in this position. The c.676C>T is a nonsense mutation that leads to premature termination of the gp91-phox protein. The brother karyotyped as 47, XXY and X chromosome analysis showed that he had inherited both his mother’s X chromosomes.
CONCLUSIONS: This study showed that the patient had gp91-phox deficient CGD while his older brother was a CGD carrier and a Klinefelter, who had inherited both his mother’s X chromosomes. This is the first report of such a concurrence in an individual, and argues for family members to be included in PID studies.
Key words: Chronic granulomatous disease, CYBB, gp91-phox, Klinefelter’s syndrome NADPHoxidase
Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of endothelial dysfunction in hypertension. In the present study, we investigated the effects of boldine on endothelial dysfunction in hypertension using spontaneously hypertensive rats (SHR), the most studied animal model of hypertension. SHR and their age-matched normotensive Wistar-Kyoto (WKY) rats were treated with boldine (20 mg/kg per day) or its vehicle, which served as control, for seven days. Control SHR displayed higher systolic blood pressure (SBP), reduced endothelium-dependent aortic relaxation to acetylcholine (ACh), marginally attenuated endothelium-independent aortic relaxation to sodium nitroprusside (SNP), increased aortic superoxide and peroxynitrite production, and enhanced p47(phox) protein expression as compared with control WKY rats. Boldine treatment significantly lowered SBP in SHR but not in WKY. Boldine treatment enhanced the maximal relaxation to ACh in SHR, but had no effect in WKY, whereas the sensitivity to ACh was increased in both SHR and WKY aortas. Boldine treatment enhanced sensitivity, but was without effect on maximal aortic relaxation responses, to SNP in both WKY and SHR aortas. In addition, boldine treatment lowered aortic superoxide and peroxynitrite production and downregulated p47(phox) protein expression in SHR aortas, but had no effect in the WKY control. These results show that boldine treatment exerts endothelial protective effects in hypertension, achieved, at least in part, through the inhibition of NADPH-mediated superoxide production.