The impact of iron deficiency on immune response in patients with inborn errors of immunity: a review of current evidence

Objective. To summarize the available data on the impact of iron deficiency on innate and adaptive immunity, focusing on the molecular mechanisms and clinical implications for patients with inborn errors of immunity. This article is a comprehensive review dedicated to describing the co-regulatory significance of iron in the formation of immune mechanisms, highlighting the role of iron deficiency as a factor in the dysregulation of various arms of the immune response.

Materials and methods. The review presents an analysis of the role of iron homeostasis in regulating the immune system. A literature search (1975-2025) was conducted in the PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and eLibrary databases. Publication selection was based on thematic relevance, belonging to peer-reviewed sources, and full-text availability. The goal of this synthesis is to provide a comprehensive picture of current knowledge.

Results. This literature review demonstrates the critical role of iron in immune system function. Iron deficiency, a global health problem, comprehensively disrupts the immune response. The impact of iron deficiency on humoral and cytokine profiles remains a subject of debate. On the part of innate immunity, IRP-dependent impairment of neutrophil differentiation and a reduced pool of dendritic cell precursors in the bone marrow are observed. This leads to defects in adaptive immunity: impaired activation of CD4+ T cells and suppression of clonal expansion of CD8+ T lymphocytes due to blockade of the tricarboxylic acid cycle and aspartate deficiency. The discovered mechanisms indicate that iron deficiency can serve as a predictor of severe infections and an ineffective vaccine response in patients with inborn errors of immunity, underscoring the need to monitor iron metabolism parameters in their management.

Conclusion. Iron deficiency in immunocompromised patients creates a vicious cycle, worsening existing immunodeficiency and increasing the risk of infections. Monitoring iron metabolism parameters and its timely correction should be considered an important component of the diagnostic algorithm in the comprehensive management of such patients.

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