Neuroimmune Regulation in Autoimmune Hemolytic Anemia: A Missing Link in Disease Persistence and Relapse

Abstract

Autoimmune Hemolytic Anemia (AIHA) is a rare but potentially life-threatening disorder characterized by the immune system's aberrant targeting and destruction of red blood cells (RBCs). Despite advances in diagnostics and immunosuppressive therapies, the disease often follows a relapsing-remitting course, the underlying mechanisms of which remain poorly understood. Emerging research points toward the neuroimmune axis as a key modulator of immune homeostasis, linking nervous system activity to immune cell behavior. The bidirectional communication between the central nervous system (CNS) and peripheral immunity, mediated by neurotransmitters, neuropeptides, and the autonomic nervous system, plays a critical role in orchestrating immune responses. Disruptions in this axis can lead to chronic inflammation, immune dysregulation, and disease relapse. In the context of AIHA, neuroimmune interactions may influence T-cell differentiation, cytokine production, and macrophage activation, all of which are central to the pathophysiology of hemolysis. This review explores the potential involvement of neuroimmune regulation in the persistence and recurrence of AIHA, highlighting mechanisms such as the hypothalamic-pituitary-adrenal (HPA) axis, vagus nerve signaling, and neuroinflammatory pathways. Understanding the neuroimmune crosstalk in AIHA may offer novel insights into disease mechanisms and therapeutic avenues.