Fatal Mycobacterium colombiense/cytomegalovirus coinfection associated with acquired immunodeficiency due to autoantibodies against interferon gamma: a case report
1 Department of Microbiology and Infectious Diseases, Centre Hospitalier Universitaire de Sherbrooke, 3001, 12ème Avenue Nord, Sherbrooke, Quebec, J1H 5N4, Canada
2 Department of Respirology, Hôpital Charles LeMoyne, Greenfield Park, Longueuil, Quebec, Canada
3 Department of Rheumatology and Allergy, Hôpital Charles LeMoyne, Greenfield Park, Longueuil, Quebec, Canada
4 Laboratoire de santé publique du Québec (LSPQ), Sainte-Anne-de-Bellevue, Quebec, Canada
5 Department of Microbiology and Immunology, Department of Pediatrics and Centre de recherche du CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada
BMC Infectious Diseases 2013, 13:24 doi:10.1186/1471-2334-13-24Published: 22 January 2013
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.
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.
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.