title: Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans.
abstract: Recently various genetic defects in immunity mediated by interferon gamma (IFN-gamma) have been described, including mutations in the IFN-gamma receptor 1 (IFN-gammaR1) and receptor 2 (IFN-gammaR2), signal transducer and activator of transcription 1 (STAT 1), and interleukin 12 receptor beta 1 (IL-12Rbeta1), and IL-12 p40 genes. These mutations are associated with the occurrence of severe infections with intracellular pathogens especially nontuberculous mycobacteria and vaccine-associated bacilli Calmette-Guérin (BCG). Here we report data on a previously healthy adult patient primarily presenting with severe infections with Burkholderia cocovenenans and subsequently Mycobacterium cheloneae. We found a strong inhibitory anti-IFN-gamma activity in the patient's plasma and identified a high-affinity neutralizing anti-IFN-gamma autoantibody. Unfortunately, the patient died due to severe sepsis before we knew the nature of the inhibitory activity. The application of alternative therapeutic approaches such as intravenous immunoglobulin or immunoadsorption may have been beneficial in this case. Screening for neutralizing anti-IFN-gamma autoantibodies should supplement testing for IFN-gamma and IL-12 pathway defects in patients with recurrent infections with intracellular pathogens, especially with nontuberculous mycobacteria.
authors.affiliation: Institute for Medical Immunology, University Hospital Charité, Humboldt University Schumannstr 20/21, D-10098 Berlin, Germany. conny.hoeflich@charite.de
authors.forename: Conny
authors.initials: C
authors.lastname: Höflich
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Simone
authors.initials: S
authors.lastname: Rosseau
authors.forename: Bettina
authors.initials: B
authors.lastname: Temmesfeld
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Döcke
authors.forename: Gerald
authors.initials: G
authors.lastname: Grütz
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
authors.forename: Elke
authors.initials: E
authors.lastname: Halle
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D019121:Burkholderia Infections / Q000276:immunology*; D042725:Burkholderia gladioli / Q000276:immunology; D003208:Concanavalin A; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology*; D016926:Mycobacterium chelonae / Q000276:immunology; D009500:Neutralization Tests
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D003208:Concanavalin A; D007371:Interferon-gamma