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

Abstract

BACKGROUND:

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.

CASE PRESENTATION:

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).

CONCLUSIONS:

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.

• Authors: Malte Roerden, Rainer Döffinger, Gabriela Barcenas-Morales, Stephan Forchhammer, Stefanie Döbele, Christoph P Berg
• Journal: BMC infectious diseases (BMC Infect Dis) Vol. 20 Issue 1 Pg. 828 (Nov 11 2020) ISSN: 1471-2334 [Electronic] England
• PMID: 33176707 (Publication Type: Case Reports, Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antiviral Agents
• Autoantibodies
• IFNG protein, human
• Immunologic Factors
• Interleukin-12
• Interferon-gamma

Topics

• Adult
• Anti-Bacterial Agents (therapeutic use)
• Antiviral Agents (therapeutic use)
• Autoantibodies (blood, immunology)
• Biopsy
• Cytomegalovirus (isolation & purification)
• Cytomegalovirus Infections (complications, diagnosis, drug therapy, virology)
• Delayed Diagnosis
• Female
• Follow-Up Studies
• Humans
• Immunologic Deficiency Syndromes (complications, diagnosis, drug therapy)
• Immunologic Factors (therapeutic use)
• Interferon-gamma (immunology, metabolism)
• Interleukin-12 (metabolism)
• Lymphadenopathy (complications, diagnosis, drug therapy, pathology)
• Mycobacterium avium Complex (isolation & purification)
• Mycobacterium avium-intracellulare Infection (complications, diagnosis, drug therapy, microbiology)
• Salmonella Infections (complications, diagnosis, drug therapy, microbiology)
• Salmonella typhimurium (isolation & purification)
• Treatment Outcome