Late-Onset Disseminated Mycobacterium avium intracellulare Complex Infection (MAC), Cerebral Toxoplasmosis and Salmonella Sepsis in a German Caucasian Patient with Unusual Anti-Interferon-Gamma IgG1 Autoantibodies

J Clin Immunol. 2015 May;35(4):361-5. doi: 10.1007/s10875-015-0161-5. Epub 2015 Apr 15.


Purpose: Since we described for the first time a patient with IgG4 autoantibodies to IFN-γ more than 10 years ago, many patients with IFN-γ IgG4 autoantibodies have been described, mostly in Mongolian/ Asian patients with a particular HLA background and in association with disseminated nontuberculous mycobacterial infections. Very recently, the first Caucasian US patient was reported and we now present the case of a 65-year old Caucasian woman with severe disseminated Mycobacterium avium infection, cerebral toxoplasmosis and salmonella sepsis who was tested positive for IFN-γ deficiency due to unusual anti-IFN-γ IgG1 autoantibodies.

Methods: IFN-γ production after ex vivo ConA stimulation of the patient's whole blood and isolated peripheral blood mononuclear cells was assessed. Anti-human IFN-γ antibodies were measured by Ig/Ig-subclass-specific ELISA. In vitro physiologic relevance and blocking capacity of IFN-γ-stimulation by patient's serum was analysed by flow cytometric assessment of cytokine-induced phosphorylation of pSTAT1(Y701).

Results: Severely impaired IFN-γ production in the patient's whole blood but normal production in peripheral blood mononuclear cells in the absence of autologous serum was observed. High titre anti-IFN-γ antibodies of the IgG1 subclass could be demonstrated in the patient's serum by ELISA. Further, the addition of patient's serum to IFN-γ-stimulated immune cells showed inhibition of STAT1 phosphorylation.

Conclusions: IFN-γ autoantibodies of any IgG-isotype should be considered in patients with severe opportunistic infections independent of age at onset and ethnicity.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Autoantibodies / immunology*
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / immunology
  • Cytokines / biosynthesis
  • Female
  • Humans
  • Immunoglobulin G / immunology*
  • Immunophenotyping
  • Interferon-gamma / immunology*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Mycobacterium avium-intracellulare Infection / diagnosis
  • Mycobacterium avium-intracellulare Infection / drug therapy
  • Mycobacterium avium-intracellulare Infection / etiology*
  • Phosphorylation
  • STAT1 Transcription Factor / metabolism
  • Salmonella Infections / etiology*
  • Sepsis / etiology*
  • Tomography, X-Ray Computed
  • Toxoplasmosis, Cerebral / diagnosis
  • Toxoplasmosis, Cerebral / etiology*


  • Autoantibodies
  • Cytokines
  • Immunoglobulin G
  • STAT1 Transcription Factor
  • Interferon-gamma