title: 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.
abstract: OBJECTIVE
  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.
authors: Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Augustenburger Platz 1/ Südstraße 2, 13353, Berlin, Germany, leif-gunnar.hanitsch@charite.de.
authors: Leif G
authors: LG
authors: Hanitsch
authors: Madlen
authors: M
authors: Löbel
authors: Holger
authors: H
authors: Müller-Redetzky
authors: Mariana
authors: M
authors: Schürmann
authors: Norbert
authors: N
authors: Suttorp
authors: Nadine
authors: N
authors: Unterwalder
authors: Ulrike
authors: U
authors: Mönnich
authors: Christian
authors: C
authors: Meisel
authors: Kirsten
authors: K
authors: Wittke
authors: Hans-Dieter
authors: HD
authors: Volk
authors: Carmen
authors: C
authors: Scheibenbogen
authors: Uwe
authors: U
authors: Kölsch
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D015270:Mycobacterium avium-intracellulare Infection / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012480:Salmonella Infections / Q000209:etiology*; D018805:Sepsis / Q000209:etiology*; D014057:Tomography, X-Ray Computed; D016781:Toxoplasmosis, Cerebral / Q000175:diagnosis / Q000209:etiology*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma