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Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy

Joerg Faber1, Claudius U Meyer, Christina Gemmer

  • 1Children's Hospital, Johannes Gutenberg-University, Mainz, Germany. faber@uni-mainz.de

The Pediatric Infectious Disease Journal
|January 6, 2006
PubMed

Insights

Two Toll-like receptor 4 (TLR4) mutations are linked to meningococcal disease in infants. These specific TLR4 gene variations increase the risk for invasive meningococcal disease in children under 12 months old.

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Toll-like receptor 4 (TLR4) plays a crucial role in the innate immune system's recognition of bacterial pathogens.
  • Bacterial infections, such as those caused by Neisseria meningitidis, can lead to severe diseases.

Purpose of the Study:

  • To investigate the association between two specific Toll-like receptor 4 (TLR4) mutations (Asp(299)Gly and Thr(399)Ile) and the risk of developing meningococcal disease.
  • To determine if these TLR4 gene variants confer susceptibility to meningococcal infections in different age groups.

Main Methods:

  • Case-control study involving 197 patients with meningococcal disease and 214 healthy controls.
  • Genotyping of TLR4 mutations (Asp(299)Gly and Thr(399)Ile) using allele-specific real-time polymerase chain reaction and direct sequencing.

Main Results:

  • No significant difference in the overall frequency of the studied TLR4 mutations was found between patients and controls.
  • A statistically significant higher frequency of these TLR4 mutations was observed in patients younger than 12 months of age (P = 0.007).

Conclusions:

  • Toll-like receptor 4 (TLR4) mutations (Asp(299)Gly and Thr(399)Ile) are identified as a potential risk factor for meningococcal disease.
  • Infants under 12 months with these TLR4 mutations show increased susceptibility to meningococcal infections, highlighting a specific genetic predisposition in this vulnerable age group.

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