Comment on “Impaired Priming and Activation of the Neutrophil NADPH Oxidase in Patients with IRAK4 or NEMO Deficiency”

We have read with interest the article published by Singh et al. in the May 4, 2009 issue of The Journal of Immunology (1). NF-κB is an essential transcription factor for multiple genes related to the immune response and development (2, 3). Previous studies by our group and others also support the concept that NF-κB activation is essential for NOX2 activity, both in vitro and in vivo. Anrather et al., using a murine model, observed a lack of NADPH oxidase activity in leukocytes, fibroblasts, and neural cells after overexpression of IκBα and in a p65/RelA knockout (4). Our previous studies with dexamethasone, a steroid that inhibits NF-κB function, demonstrated inhibition of the phagocyte NADPH oxidase system at the transcriptional level (CYBB and NCF1 genes) in THP-1 myelomonocytic cells (5). Using U937 cells with a stable transfected repressor of NF-κB (IκBα-S32A/s36a) and EBV-transformed B cells from two patients with ectodermal dysplasia and immunodeficiency (EDA-ID), we found that proper binding of NF-κB is necessary for human CYBB and NCF1 gene expression and normal NADPH oxidase activity (6). Recently, our group observed that mononuclear cells from patients with EDA-ID produce less superoxide than normal control cells (Fig. 1). Taken together, our current and previous observations (5, 6), and those of Singh et al. (1) all corroborate the essential role of NF-κB for proper function of the human phagocyte NADPH oxidase system.