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• 作者：Leif G. Hanitsch ; Madlen L?bel ; Holger Müller-Redetzky…
• 关键词：anticytokine antibody ; autoantibody ; interferon gamma (IFN ; γ) ; IgG1 ; non ; tuberculous mycobacterium ; MAC ; NTM ; MSMD ; toxoplasmosis ; secondary autoimmune ; mediated immunodeficiency
• 刊名：Journal of Clinical Immunology
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：35
• 期：4
• 页码：361-365
• 全文大小：589 KB
• 参考文献：1.Hoflich C, Sabat R, Rosseau S, Temmesfeld B, Slevogt H, Docke WD, et al. Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans. Blood. 2004;103:673-.View Article PubMed
  2.Doffinger R, Helbert MR, Barcenas-Morales G, Yang K, Dupuis S, Ceron-Gutierrez L, et al. Autoantibodies to interferon-gamma in a patient with selective susceptibility to mycobacterial infection and organ-specific autoimmunity. Clin Infect Dis. 2004;38:e10-.View Article PubMed
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  7.Ishii T, Tamura A, Matsui H, Nagai H, Akagawa S, Hebisawa A, et al. Disseminated Mycobacterium avium complex infection in a patient carrying autoantibody to interferon-gamma. J Infect Chemother. 2013;19:1152-.View Article PubMed
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• 作者单位：Leif G. Hanitsch (1)
  Madlen L?bel (1)
  Holger Müller-Redetzky (2)
  Mariana Schürmann (2)
  Norbert Suttorp (2)
  Nadine Unterwalder (3)
  Ulrike M?nnich (3)
  Christian Meisel (1) (3)
  Kirsten Wittke (1)
  Hans-Dieter Volk (1) (4)
  Carmen Scheibenbogen (1) (4)
  Uwe K?lsch (3)
  
  1. Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Augustenburger Platz 1/ Südstra?e 2, 13353, Berlin, Germany
  2. Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité University Medicine Berlin, Campus Virchow, Augustenburger Platz 1, 13353, Berlin, Germany
  3. Labor Berlin GmbH, Immunology Department, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany
  4. Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Berlin, Germany
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Immunology
  Infectious Diseases
  Internal Medicine
  Medical Microbiology
  
• 出版者：Springer Netherlands
• ISSN：1573-2592

文摘

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 pSTAT1Y701. 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.