Journal of Clinical Immunology

, Volume 31, Issue 2, pp 265–271 | Cite as

Novel STAT1 Alleles in a Patient with Impaired Resistance to Mycobacteria

  • Ines Ackerl Kristensen
  • Jens Erik Veirum
  • Bjarne Kuno Møller
  • Mette Christiansen
Article

Abstract

Partial defects in interferon (IFN)-γ signaling lead to susceptibility to infections with nontuberculous mycobacteria. The receptors for IFN-α and IFN-γ activate components of the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway. Some defects in STAT1 mainly affect IFN-γ signaling, thus resulting in mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a severe disease but patients show a favorable response to anti-mycobacterial chemotherapy. Other defects in STAT1 affect both IFN-α and IFN-γ signaling resulting in mycobacterial and lethal viral disease. We report here a patient with two novel STAT1 alleles, which in combination results in a recessive trait with partial STAT1 deficiency and mycobacterial disease. Cells from the patient did respond to mycobacterial antigen, but both the expression of STAT1 and phosphorylation of STAT1 in response to IFN-γ treatment were reduced. This is the first report of a mutation in the N-terminal part of STAT1 involved in causing mycobacterial disease.

Keywords

Human immunodeficiency diseases transcription factors signal transduction nontuberculous mycobacteria MSMD STAT1 

Abbreviations

IFN-γ

Interferon-γ

MSMD

Mycobacterial disease

JAK

Janus kinase

STAT1

Signal transducer and activator of transcription-1

IFNGR

IFN-γ receptor

GAF

Gamma-activated factor

GAS

Gamma-activated sequences

ISGF3

IFN-stimulated genes factor 3

ISRE

IFN-α sequence response element

PHA

Phytohemagglutinin

PWM

Pokeweed mitogen

HLA

Human leukocyte antigen

PPD

Purified protein derivative

NK

Natural killer

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ines Ackerl Kristensen
    • 1
  • Jens Erik Veirum
    • 2
  • Bjarne Kuno Møller
    • 3
  • Mette Christiansen
    • 3
  1. 1.Department of PediatricsCopenhagen University HospitalRigshospitaletDenmark
  2. 2.Department of PediatricsAarhus University HospitalSkejbyDenmark
  3. 3.Department of Clinical ImmunologyAarhus University HospitalSkejbyDenmark

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