title: Fatal Mycobacterium colombiense/cytomegalovirus coinfection associated with acquired immunodeficiency due to autoantibodies against interferon gamma: a case report.
abstract: BACKGROUND
  Reports of acquired immunodeficiency due to autoantibodies against interferon gamma in the adult population are increasing. The interleukin-12-dependent interferon-gamma axis is a major regulatory pathway of cell-mediated immunity and is critical for protection against a few intracellular organisms, including non-tuberculous mycobacteria and Salmonella spp. We report the first case of a fatal disseminated Mycobacterium colombiense/cytomegalovirus coinfection in an adult woman associated with the acquisition of autoantibodies against interferon-gamma.
  
  
  METHODS
  A 49-year-old woman, born to nonconsanguineous parents in Laos, but who had lived in Canada for the past 30 years, presented with a 1-month history of weight loss, fatigue, cough, and intermittent low-grade fever. A thoracic computed tomography scan revealed an 8 × 7 cm irregular mass impacting the right superior lobar bronchus along with multiple mediastinal and hilar adenopathies. On the fourth day of admission, the patient developed fever with purulent expectorations. Treatment for a post-obstructive bacterial pneumonia was initiated while other investigations were being pursued. Almost every culture performed during the patient's hospitalization was positive for M. colombiense. Given the late presentation of symptoms - at the age of 49 years - and the absence of significant family or personal medical history, we suspected an acquired immunodeficiency due to the presence of anti-interferon-gamma autoantibodies. This was confirmed by their detection at high levels in the plasma and a STAT1 phosphorylation assay on human monocytes. The final diagnosis was immunodeficiency secondary to the production of autoantibodies against interferon-gamma, which resulted in a post-obstructive pneumonia and disseminated infection of M. colombiense. The clinical course was complicated by the presence of a multiresistant Pseudomonas aeruginosa post-endobronchial ultrasound mediastinitis, cytomegalovirus pneumonitis with dissemination, and finally, susceptible P. aeruginosa ventilator-associated pneumonia with septic shock and multiple organ failure, leading to death despite appropriate antibacterial and anti-mycobacterial treatment.
  
  
  CONCLUSIONS
  Although rare, acquired immunodeficiency syndromes should be considered in the differential diagnosis of patients with severe, persistent, or recurrent infections. Specifically, severe non-tuberculous mycobacteria or Salmonella infections in adults without any other known risk factors may warrant examination of autoantibodies against interferon-gamma because of their increasing recognition in the literature.
authors: Department of Microbiology and Infectious Diseases, Centre Hospitalier Universitaire de Sherbrooke, 3001, 12ème Avenue Nord, Sherbrooke, Quebec J1H 5N4, Canada. sebastien.poulin@usherbrooke.ca
authors: Sébastien
authors: S
authors: Poulin
authors: Claude
authors: C
authors: Corbeil
authors: Mélanie
authors: M
authors: Nguyen
authors: Anik
authors: A
authors: St-Denis
authors: Lise
authors: L
authors: Côté
authors: Françoise
authors: F
authors: Le Deist
authors: Alex
authors: A
authors: Carignan
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D060085:Coinfection; D003586:Cytomegalovirus Infections / Q000209:etiology*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D008875:Middle Aged; D009164:Mycobacterium Infections / Q000209:etiology*
chemical_list: D001323:Autoantibodies; D007371:Interferon-gamma