Michael John Dochniak
Neonatal sepsis remains a major global cause of infant mortality, with preterm neonates facing the greatest risk of rapid deterioration, septic shock, and poor outcomes. Current standard care, which relies mostly on broad-spectrum antibiotics and supportive interventions, does not target the core immunological dysfunctions of the preterm infant. While past immunomodulatory approaches, such as intravenous immunoglobulin, have shown little benefit, advances in immunology now highlight the promise of targeted therapies. This review summarizes the complex, multifactorial immune deficits seen in premature neonates, including profound hypogammaglobulinemia, compromised physical barriers, and adaptive T-cell immaturity. Furthermore, it discusses the innovative therapeutic potential of IgE-antigen complexes (IgE-ACs) targeting the CD23 (FcεRII) receptor. By engaging this pathway, IgE-ACs can modulate immune signaling to dampen hyper-inflammatory responses, enhance pathogen clearance without excessive inflammation, accelerate adaptive T-cell priming, and reduce the risk of post-infectious immune paralysis. These mechanisms point to IgE-AC/CD23 modulation as a novel and potentially transformative strategy to improve outcomes in neonatal intensive care.