title: Chinese patients with defective IL-12/23-interferon-gamma circuit in Taiwan: partial dominant interferon-gamma receptor 1 mutation presenting as cutaneous granuloma and IL-12 receptor beta1 mutation as pneumatocele.
abstract: BACKGROUND
  IL-12/23-interferon-gamma circuit enhances reactive oxygen species (ROS) synthesis in macrophage to attack intracellular pathogens such as mycobacteria and salmonella. Defective ROS in patients with chronic granulomatous disease (CGD) have increased susceptibility to these pathogens. However, patients with defective IL-12/23-interferon-gamma circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella.
  
  
  OBJECTIVE
  The purpose of this study was to identify Taiwanese patients with defective IL-12/23-IFN-gamma circuit.
  
  
  METHODS
  In a long-term molecular study of primary immunodeficiency diseases (PIDD), the tentative CGD patients presenting with Bacille Calmette-Guerin (BCG)-induced infection, refractory atypical mycobacterial cutaneous granuloma and osteomyelitis, recurrent salmonella sepsis, and pneumatocele were studied for the IL-12/23-IFN-gamma circuit. ROS was first measured to exclude CGD. Candidate genes of IL12RB1, IFNRG1, IL12p40, IFNRG2, signal transducer and activator of transcription-1, and NF-kappaB essential modulator and their encoding protein expressions were analyzed.
  
  
  RESULTS
  Of the 175 Taiwanese PIDD patients during a 28-year period, three patients from two unrelated families were identified with the hotspot INFRG1 deletion mutation (818del4) and had CGD features, presenting as cutaneous granuloma, and multiple osteomyelitis infected by non-tuberculosis mycobacteria, Mycobacteria avium complex and Mycobacterium scrofulaceum. Another with mis-sense IL12RB1 mutation (Arg211Pro) was noted as recurrent Salmonella enteritidis D sepsis and pneumatocele.
  
  
  CONCLUSIONS
  Patients with defective IL-12/23-IFN-gamma circuit may resemble or overlap CGD manifestations of refractory cutaneous atypical mycobacterial granuloma and salmonella pneumatocele.
authors.affiliation: Primary Immunodeficiency Care And Research (PICAR) Institute, Chang Gung Memory and Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. wen2707@hotmail.com
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Huang
authors.forename: Tzou-Yien
authors.initials: TY
authors.lastname: Lin
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Alex M
authors.initials: AM
authors.lastname: Wong
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Chiu
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D005799:Genes, Dominant; D006099:Granuloma / Q000175:diagnosis* / Q000382:microbiology; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006547:Hernia / Q000175:diagnosis* / Q000382:microbiology; D006801:Humans; D007223:Infant; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000235:genetics*; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D008171:Lung Diseases / Q000175:diagnosis* / Q000382:microbiology; D008297:Male; D009154:Mutation / Q000235:genetics; D009165:Mycobacterium Infections, Nontuberculous / Q000150:complications / Q000235:genetics / Q000382:microbiology; D010019:Osteomyelitis / Q000235:genetics / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics*; D012480:Salmonella Infections / Q000150:complications / Q000382:microbiology; D012871:Skin Diseases / Q000175:diagnosis* / Q000382:microbiology; D013624:Taiwan; D014057:Tomography, X-Ray Computed; D000096743:Interferon gamma Receptor
chemical_list: D053711:Interleukin-12 Receptor beta 1 Subunit; D053646:Interleukin-2 Receptor beta Subunit; D017382:Reactive Oxygen Species; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor