Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs)

Wen I. Lee, Jing Long Huang, Kuo Wei Yeh, Tang Her Jaing, Tzou Yien Lin, Yhu Chering Huang, Cheng Hsun Chiu

Research output: Contribution to journalReview article

47 Citations (Scopus)

Abstract

Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG) or nontuberculous mycobacteria (NTM), and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell) connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs) have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID) including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM) (CD40L mutation), CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations), chronic granulomatous disease (CGD) and hyper IgE recurrent infection syndromes (HIES). The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD) phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8) for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one), presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ), which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively persistent MSMD phenotype lacking BCG-induced diseases.

Original languageEnglish
Pages (from-to)750-758
Number of pages9
JournalJournal of the Formosan Medical Association
Volume110
Issue number12
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Keywords

  • Bacille Calmette-Guerin (BCG) infection (BCGitis or BCGosis)
  • IL-12 receptor β1 (IL12RB1)
  • IL-12/23-IFN-γ circuit
  • Interferon-γ receptor 1 (IFNGR1)
  • Mendelian susceptibility to mycobacterial disease (MSMD)
  • Primary immunodeficiency diseases (PIDs)

ASJC Scopus subject areas

  • Medicine(all)

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