Chinese patients with defective IL-12/23-interferon-γ circuit in Taiwan: Partial dominant interferon-γ receptor 1 mutation presenting as cutaneous granuloma and IL-12 receptor β1 mutation as pneumatocele

Wen I. Lee, Jing Long Huang, Tzou Yien Lin, Chuen Hsueh, Alex M. Wong, Meng Ying Hsieh, Cheng Hsun Chiu, Tang Her Jaing

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: IL-12/23-interferon-γ 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-γ circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella. Aim: The purpose of this study was to identify Taiwanese patients with defective IL-12/23-IFN-γ circuit. Patients and 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-γ circuit. ROS was first measured to exclude CGD. Candidate genes of IL12RB1, IFNRG1, IL12p40, IFNRG2, signal transducer and activator of transcription-1, and NF-κB 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. Conclusion: Patients with defective IL-12/23-IFN-γ circuit may resemble or overlap CGD manifestations of refractory cutaneous atypical mycobacterial granuloma and salmonella pneumatocele.

Original languageEnglish
Pages (from-to)238-245
Number of pages8
JournalJournal of Clinical Immunology
Volume29
Issue number2
DOIs
Publication statusPublished - Mar 2009
Externally publishedYes

Fingerprint

Interleukin-12 Receptors
Interferon Receptors
Interleukin-23
Interleukin-12
Granuloma
Taiwan
Chronic Granulomatous Disease
Interferons
Skin
Mutation
Salmonella
Reactive Oxygen Species
Osteomyelitis
Mycobacterium
Mycobacterium scrofulaceum
Sepsis
STAT1 Transcription Factor
Mycobacterium avium Complex
Salmonella enteritidis
Sequence Deletion

Keywords

  • Bacille Calmette-Guerin infection (BCGitis)
  • Cutaneous granuloma
  • IL-12 receptor β1 (IL12RB1)
  • IL-12/23-IFN-γ circuit
  • Interferon-γ receptor 1 (IFNGR1)
  • Mendelian susceptibility to mycobacterial disease (MSMD)
  • Pneumatocele

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chinese patients with defective IL-12/23-interferon-γ circuit in Taiwan : Partial dominant interferon-γ receptor 1 mutation presenting as cutaneous granuloma and IL-12 receptor β1 mutation as pneumatocele. / Lee, Wen I.; Huang, Jing Long; Lin, Tzou Yien; Hsueh, Chuen; Wong, Alex M.; Hsieh, Meng Ying; Chiu, Cheng Hsun; Jaing, Tang Her.

In: Journal of Clinical Immunology, Vol. 29, No. 2, 03.2009, p. 238-245.

Research output: Contribution to journalArticle

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title = "Chinese patients with defective IL-12/23-interferon-γ circuit in Taiwan: Partial dominant interferon-γ receptor 1 mutation presenting as cutaneous granuloma and IL-12 receptor β1 mutation as pneumatocele",
abstract = "Background: IL-12/23-interferon-γ 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-γ circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella. Aim: The purpose of this study was to identify Taiwanese patients with defective IL-12/23-IFN-γ circuit. Patients and 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-γ circuit. ROS was first measured to exclude CGD. Candidate genes of IL12RB1, IFNRG1, IL12p40, IFNRG2, signal transducer and activator of transcription-1, and NF-κB 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. Conclusion: Patients with defective IL-12/23-IFN-γ circuit may resemble or overlap CGD manifestations of refractory cutaneous atypical mycobacterial granuloma and salmonella pneumatocele.",
keywords = "Bacille Calmette-Guerin infection (BCGitis), Cutaneous granuloma, IL-12 receptor β1 (IL12RB1), IL-12/23-IFN-γ circuit, Interferon-γ receptor 1 (IFNGR1), Mendelian susceptibility to mycobacterial disease (MSMD), Pneumatocele",
author = "Lee, {Wen I.} and Huang, {Jing Long} and Lin, {Tzou Yien} and Chuen Hsueh and Wong, {Alex M.} and Hsieh, {Meng Ying} and Chiu, {Cheng Hsun} and Jaing, {Tang Her}",
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T2 - Partial dominant interferon-γ receptor 1 mutation presenting as cutaneous granuloma and IL-12 receptor β1 mutation as pneumatocele

AU - Lee, Wen I.

AU - Huang, Jing Long

AU - Lin, Tzou Yien

AU - Hsueh, Chuen

AU - Wong, Alex M.

AU - Hsieh, Meng Ying

AU - Chiu, Cheng Hsun

AU - Jaing, Tang Her

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N2 - Background: IL-12/23-interferon-γ 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-γ circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella. Aim: The purpose of this study was to identify Taiwanese patients with defective IL-12/23-IFN-γ circuit. Patients and 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-γ circuit. ROS was first measured to exclude CGD. Candidate genes of IL12RB1, IFNRG1, IL12p40, IFNRG2, signal transducer and activator of transcription-1, and NF-κB 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. Conclusion: Patients with defective IL-12/23-IFN-γ circuit may resemble or overlap CGD manifestations of refractory cutaneous atypical mycobacterial granuloma and salmonella pneumatocele.

AB - Background: IL-12/23-interferon-γ 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-γ circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella. Aim: The purpose of this study was to identify Taiwanese patients with defective IL-12/23-IFN-γ circuit. Patients and 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-γ circuit. ROS was first measured to exclude CGD. Candidate genes of IL12RB1, IFNRG1, IL12p40, IFNRG2, signal transducer and activator of transcription-1, and NF-κB 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. Conclusion: Patients with defective IL-12/23-IFN-γ circuit may resemble or overlap CGD manifestations of refractory cutaneous atypical mycobacterial granuloma and salmonella pneumatocele.

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KW - IL-12/23-IFN-γ circuit

KW - Interferon-γ receptor 1 (IFNGR1)

KW - Mendelian susceptibility to mycobacterial disease (MSMD)

KW - Pneumatocele

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