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

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.