Upregulation of interferon-γ activation in patients with anti-interferon-γ autoantibodies immunodeficiency syndrome: insights from single-cell analysis

Key Points

Autoantibody generation is driven by the upregulation of interferon-γ, highlighting its role in immunodeficiency.
The analysis shows CD4+ T cells and monocyte interactions are pivotal in sustaining this immune response.
Detailed single-cell mapping reveals unique T- and B-cell trajectories underpinning the disorder.
Identifying specific gene expressions may guide effective therapeutic interventions for patients.

Abstract

In summary, this first single-cell atlas maps AIGAs immunodeficiency syndrome as a Th1-skewed, IFN-γ-driven disorder sustained by CD4+ Tem-CD14+ monocyte crosstalk. It combines T-cell activation, expanded Th1 and ISG+ B cells, and loss of memory/plasma B cells to drive autoantibody generation. Skewed T- and B-cell trajectories and polygenic up-regulation of interferon/HLA genes provide a clear mechanistic rationale for targeted therapy.

Upregulation of interferon-γ activation in patients with anti-interferon-γ autoantibodies immunodeficiency syndrome: insights from single-cell analysis

Key Points

Abstract

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