title: Enhanced generation of reactive oxygen species by interferon-γ may have contributed to successful treatment of invasive pulmonary aspergillosis in a patient with chronic granulomatous disease.
abstract: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication of chronic granulomatous disease (CGD), a rare inherited disorder of phagocytes that is characterized by a defect in the production of reactive oxygen species (ROS) caused by mutations in NADPH oxidase 2. Here, we report a case of successful treatment of IPA complicated with CGD by the administration of interferon-γ (IFN-γ) in combination with voriconazole. The patient carried a splice site mutation in the CYBB gene, and the neutrophils could produce a certain amount of ROS. In this case, augmentation of ROS generation in the patient's neutrophils was observed after in vivo IFN-γ treatment, which may be attributable to the induction of a normal CYBB gene in the myeloid progenitor cells. This treatment, in combination with voriconazole, may have contributed to the reversal of IPA in this patient. These results suggest that the in vivo use of IFN-γ may augment ROS generation in CGD neutrophils, thus leading to the successful treatment of severe IPA.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan. kouhei@kuhp.kyoto-u.ac.jp
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamashita
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arai
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Mizugishi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ueyama
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002460:Cell Line; D005091:Exons; D023061:Gene Order; D006105:Granulomatous Disease, Chronic / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology / Q000627:therapeutic use; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D000935:Antifungal Agents; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D007371:Interferon-gamma; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases