Detection of Neutralizing Anti-Type 1 Interferon Autoantibodies.

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Autoantibodies neutralizing type 1 interferons (T1IFNs) are linked to severe COVID-19.
• These autoantibodies are prevalent in older adults and individuals with thymic defects.
• Early detection of autoantibody-positive individuals can enable targeted interventions.

Purpose of the Study:

• To establish a workflow for rapidly identifying individuals with anti-T1FN autoantibodies.
• To provide protocols for large-scale screening and functional validation of autoantibodies.

Main Methods:

• Multiplex particle-based bead assay for screening anti-T1FN autoantibody binding levels.
• Functional assay (pSTAT1) to assess the neutralizing capacity of patient plasma autoantibodies.
• Protocols for coupling type 1 interferons (IFN-α, IFN-β, IFN-ω) to magnetic beads.

Main Results:

• Developed and validated assays for high-throughput screening of autoantibodies.
• Demonstrated the ability to identify autoantibody-positive individuals within a large cohort.
• Established a functional assay to confirm the neutralizing activity of identified autoantibodies.

Conclusions:

• The presented workflow enables rapid identification of individuals with neutralizing autoantibodies against T1FNs.
• This capability is crucial for preventing critical COVID-19 outcomes in at-risk populations.
• The protocols facilitate targeted therapeutic strategies for individuals with specific autoAbs.