title: Monocyte/macrophage-specific NADPH oxidase contributes to antimicrobial host defense in X-CGD.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that is characterized by susceptibility to bacterial and fungal infections. Various mutations in CYBB encoding the gp91(phox) subunit of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase impair the respiratory burst of all types of phagocytic cells and result in X-linked CGD (X-CGD).
  
  
  OBJECTIVE
  We here sought to evaluate the underlying cause in an attenuated phenotype in an X-CGD patient. The patient is a 31-year-old male who had been diagnosed as having X-CGD based on the absence of nitroblue tetrazolium reduction and the presence of a CYBB mutation at the age of 1 year. He has been in good health after overcoming recurrent bacterial infections in infancy.
  
  
  METHODS
  We investigated genomic DNA analysis of CYBB gene, residual activity of NADPH oxidase, and expression of gp91(phox) in both polymorphonuclear leukocytes (PMNs) and monocytes/macrophages in the present patient.
  
  
  RESULTS
  Although his underlying germline mutation, c.1016C>A (p.P339H) in the CYBB gene, was identified in both PMNs and monocytes, the expression and functional activity of gp91(phox) retained in monocytes/macrophages, in stark contrast to markedly reduced PMNs.
  
  
  CONCLUSIONS
  Our results indicate that residual reactive oxygen intermediates (ROI) production in PMNs plays an important role in infantile stage in X-CGD, but thereafter retained function of monocytes/macrophages might compensate for the function of NADPH oxidase deficient PMNs and might be an important parameter for predicting the prognosis of X-CGD patients.
authors: Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan, okura@med.hokudai.ac.jp.
authors: Yuka
authors: Y
authors: Okura
authors: Masafumi
authors: M
authors: Yamada
authors: Futoshi
authors: F
authors: Kuribayashi
authors: Ichiro
authors: I
authors: Kobayashi
authors: Tadashi
authors: T
authors: Ariga
mesh_terms: D000328:Adult; D002461:Cell Line, Transformed; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation; D015870:Gene Expression; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007239:Infections / Q000209:etiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D020871:RNA Stability; D016897:Respiratory Burst / Q000235:genetics
chemical_list: D003573:Cytochrome b Group; D008562:Membrane Glycoproteins; C036888:cytochrome b558; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases