Development and consequences of red blood cell autoantibodies: warm autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is a rare disorder caused by loss of tolerance to red blood cell (RBC) antigens, leading to their destruction by autoantibodies. AIHA can occur as a primary condition or secondary to infections, malignancies, or immune-modulating therapies, such as immune checkpoint inhibitors. This review focuses on the roles of B and T cells in disease initiation and progression of warm AIHA. We discuss recent studies highlighting the importance of dysregulated CD4+ T cells in driving autoreactive B cell responses and autoantibody production and highlight a new role for purinergic signaling in contributing to T cell dysfunction. This dysfunction results in an imbalance between T regulatory cells and proinflammatory Th17 cells, further exacerbating the autoimmune response. Treatment strategies have variable success, with relapse rates of up to 50% and mortality in ∼11%. As such, we also discuss emerging therapeutic strategies, which may potentially lead to more effective and targeted treatments for this serious condition.