Simultaneous disseminated infections with intracellular pathogens: an intriguing case report of adult-onset immunodeficiency with anti-interferon-gamma autoantibodies

• Published in: BMC infectious diseases Vol. 20; no. 1; p. 828
• Main Authors: Roerden, Malte, Döffinger, Rainer, Barcenas-Morales, Gabriela, Forchhammer, Stephan, Döbele, Stefanie, Berg, Christoph P
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11-11-2020; BioMed Central; BMC
• Subjects: Abdomen; Acquired immune deficiency syndrome; Adult; AIDS; Analysis; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antiviral Agents - therapeutic use; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biopsy; Blood; Breast implants; Case Report; Case reports; Colitis; Cytomegalovirus; Cytomegalovirus - isolation & purification; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - virology; Delayed Diagnosis; Development and progression; Diagnosis; Diarrhea; Female; Follow-Up Studies; Granulomas; HIV; Human immunodeficiency virus; Humans; Immunodeficiency; Immunologic deficiency syndromes; Immunologic Deficiency Syndromes - complications; Immunologic Deficiency Syndromes - diagnosis; Immunologic Deficiency Syndromes - drug therapy; Immunologic Factors - therapeutic use; Immunotherapy; Infections; Infectious diseases; Inflammatory bowel disease; Interferon; Interferon gamma; Interferon gamma autoantibodies; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin 12; Interleukin-12 - metabolism; Interleukins; Intracellular; Laboratories; Lymph nodes; Lymphadenopathy; Lymphadenopathy - complications; Lymphadenopathy - diagnosis; Lymphadenopathy - drug therapy; Lymphadenopathy - pathology; Lymphatic system; Lymphocytes B; Microorganisms; Monoclonal antibodies; Mycobacterium avium Complex - isolation & purification; Mycobacterium avium-intracellulare Infection - complications; Mycobacterium avium-intracellulare Infection - diagnosis; Mycobacterium avium-intracellulare Infection - drug therapy; Mycobacterium avium-intracellulare Infection - microbiology; Mycobacterium infections; Neutralizing; Non-tuberculous mycobacteria; Non-typhoidal salmonella; Pain; Pathogens; Patients; Persistent infection; Rituximab; Salmonella; Salmonella Infections - complications; Salmonella Infections - diagnosis; Salmonella Infections - drug therapy; Salmonella Infections - microbiology; Salmonella typhimurium - isolation & purification; Signal transduction; Signaling; Thorax; Transplants & implants; Treatment Outcome; Tuberculosis; Weight loss; γ-Interferon; Germany; Interferon gamma autoantibodies; cytomegalovirus; Non-tuberculous mycobacteria; Rituximab; Interleukin 12; Non-typhoidal salmonella; Interferon gamma
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-020-05553-y

Severe and disseminated non-tuberculous mycobacterial (NTM) infections are frequently linked to a genetic predisposition but acquired defects of the interferon gamma (IFNγ) / interleukin 12 (IL-12) pathway need to be considered in adult patients with persistent or recurrent infections. Neutralizing anti-IFNγ autoantibodies disrupting IFNγ signalling have been identified as the cause of a severe and unique acquired immunodeficiency syndrome with increased susceptibility to NTM and other intracellular pathogens.
An adult Asian female with a previous history of recurrent NTM infections presented with persistent diarrhea, abdominal pain, night sweats and weight loss. Severe colitis due to a simultaneous infection with cytomegalovirus (CMV) and Salmonella typhimurium was diagnosed, with both pathogens also detectable in blood samples. Imaging studies further revealed thoracic as well as abdominal lymphadenopathy and a disseminated Mycobacterium intracellulare infection was diagnosed after a lymph node biopsy. Further diagnostics revealed the presence of high-titer neutralizing anti-IFNγ autoantibodies, allowing for the diagnosis of adult-onset immunodeficiency with anti-IFNγ autoantibodies (AIIA).
We here present a severe case of acquired immunodeficiency with anti-IFNγ autoantibodies with simultaneous, disseminated infections with both viral and microbial pathogens. The case illustrates how the diagnosis can cause considerable difficulties and is often delayed due to unusual presentations. Histological studies in our patient give further insight into the pathophysiological significance of impaired IFNγ signalling. B-cell-depleting therapy with rituximab offers a targeted treatment approach in AIIA.