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


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.


Human immunodeficiency diseases transcription factors signal transduction nontuberculous mycobacteria MSMD STAT1 





Mycobacterial disease


Janus kinase


Signal transducer and activator of transcription-1


IFN-γ receptor


Gamma-activated factor


Gamma-activated sequences


IFN-stimulated genes factor 3


IFN-α sequence response element




Pokeweed mitogen


Human leukocyte antigen


Purified protein derivative


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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