Anti-interferon-γ autoantibody-associated immunodeficiency.

Area of Science:

• Immunology
• Infectious Diseases
• Genetics

Background:

• Anticytokine autoantibodies represent an emerging disease etiology disrupting cytokine functions.
• Anti-interferon gamma autoantibodies (AIGAs) were initially linked to severe mycobacterial infections, mimicking genetic defects in the IL-12/IFN-γ pathway.
• Over 600 cases, primarily from Southeast Asia, have been reported in the last decade.

Purpose of the Study:

• To characterize the clinical and genetic features of anti-interferon gamma autoantibodies (AIGAs).
• To understand the spectrum of infections associated with AIGAs.
• To define AIGAs as a distinct form of late-onset immunodeficiency.

Main Methods:

• Clinical case review and analysis of reported AIGA cases.
• Genetic association studies identifying specific HLA class II alleles.
• Analysis of infection patterns in patients with AIGAs.

Main Results:

• AIGAs are associated with specific HLA class II molecules, indicating a genetic predisposition in certain ethnic groups.
• Salmonellosis and herpes zoster reactivation occur in over half of AIGA patients.
• AIGAs are implicated in severe Talaromyces marneffei infections in HIV-negative individuals.

Conclusions:

• AIGAs represent a significant cause of late-onset immunodeficiency.
• This condition confers susceptibility to severe mycobacterial, bacterial, and fungal infections.
• Understanding AIGAs is crucial for diagnosing and managing these complex infections.