Can low serum iron concentration impact immunity?

Impact of Low Serum Iron on Immunity

Yes, low serum iron concentration significantly impairs both innate and adaptive immunity, increasing susceptibility to infections and reducing vaccine efficacy. 1, 2

Effects on Innate Immunity

• Neutrophil function: Iron is essential for the antimicrobial oxidative burst inside neutrophils, which is crucial for pathogen killing 1, 2
• Macrophage function: Iron is required for proper polarization and differentiation of macrophages during infection 1
• Inflammatory response: Iron is necessary for binding activity of proinflammatory transcription factors 2

Effects on Adaptive Immunity

T Cell Immunity

• Human studies show that iron deficiency is associated with:
  • Reduced proportion of mature T cells 1
  • Impaired T cell activation and proliferation 1
  • Decreased T cell percentage (which can improve with iron supplementation) 1

B Cell Immunity and Antibody Production

• Recent evidence demonstrates that serum iron levels are critical for:
  • Primary and memory B cell responses 1
  • Vaccine efficacy 1, 3
  • In vivo studies show iron-deficient mice have impaired B cell proliferation and attenuated antibody responses 1

Clinical Evidence

• A randomized birth cohort study in Kenyan infants showed that:

  • Anemia and iron deficiency at vaccination predicted decreased responses to diphtheria, pertussis, and pneumococcal vaccines 1
  • Iron supplementation improved primary response to measles vaccines 1, 4

• Translational research indicates that iron deficiency in piglets and hepcidin-induced hypoferremia in mice and IRIDA patients:

  • Negatively influences responses to vaccines and infections 1, 3
  • Providing extra iron improved vaccination response in hypoferremic animals 3

• In mice with influenza infection, hypoferremia:

  • Blunted T cell, B cell, and neutralizing antibody responses 3
  • Allowed virus to persist longer
  • Exacerbated lung inflammation and morbidity 3, 4

Molecular Mechanisms

• Lymphocyte proliferation depends on iron acquisition through transferrin receptor 1 (TfR1) 1
• A rare mutation in TfR1 (p.Tyr20His) causes combined immunodeficiency due to compromised T and B cell proliferation 1
• The intensified metabolism of activated lymphocytes requires enhanced iron acquisition 3, 4

Clinical Implications

• For vaccination: Consider iron status before vaccination, especially in high-risk populations 1, 4
• During infections: The body activates "nutritional immunity" by sequestering iron from pathogens, which may temporarily worsen iron status but limit pathogen growth 2
• For supplementation: Complete antibiotic treatment before administering iron supplementation during active infections 2

Common Pitfalls

• Overlooking iron status: Failing to assess iron status in patients with recurrent infections or poor vaccine responses
• Inappropriate timing: Administering IV iron during active infections can increase infection risk by 16% 2
• Confounding factors: Clinical studies on iron and immunity often have methodological heterogeneity and quality issues 1

While further clinical trials are needed to establish exact protocols, the evidence clearly shows that maintaining adequate iron status is important for optimal immune function and response to vaccines.