A toll-like receptor 4 variant is associated with fatal outcome in children with invasive meningococcal disease

Aims: Toll-like receptor 4 (TLR4) is the major endotoxin signalling receptor of the innate immune system and is required for efficient recognition of bacterial infections. Here, we analysed a possible association between the TLR4 variant Asp299Gly and disease outcome in children with invasive meningococcal disease. Methods: In total, 197 children with invasive meningococcal disease were analysed for the TLR4 Asp299Gly variant. Genotyping results were correlated with mortality, the frequency of ventilation support, application of inotropic substances, skin grafting, and limb loss. Results: The overall Asp299Gly allele frequency was 9.4%. Detection of a heterozygous Asp299Gly TLR4 mutation was significantly associated with fatal outcome (non-survivor group: 31.6% vs. survivor group: 12.1%; p = 0.021) and was even more pronounced in patients with disease onset less than 24 months of age (non-survivor group: 42.8% vs. survivor group: 10.2%; p = 0.006). In this age group, ventilation support was also more frequent in patients with the Asp299Gly genotype (37.5% vs. 6.2%). Conclusion: Our data suggest that the heterozygous TLR4 Asp299Gly genotype is associated with an increased mortality in children with invasive meningococcal disease.