The findings suggest that MBL2 supports innate immune defence against meningococcal disease in the early months of life, before acquired immunity is sufficiently robust for effective natural protection.
Genetic variants associated with severity of meningococcal disease, including the IgG Fc receptor (FCγRII)-A484T, interleukin-10 (IL-10)-A1082G, -C819T, and -C627A, IL-4-C589T, mannose binding lectin-2 (MBL2)-A/O, -H/L, -P/Q, and -X/Y, toll-like receptor 2 (TLR2)-G2408A, TLR4-A12874G and -C13174T, and TLR9-T1237C and -T1486C were determined by real-time PCR (RT-PCR) for 271 HIV-infected subjects (median, 17 years).
Our data suggest that MBL exon 1 structural variants are significantly associated with susceptibility to childhood meningococcal disease in an age-dependent manner.
These results suggest that MBLnot only is involved in complement activation but also is a potent regulator of inflammatory pathways and, as such, may affect the severity of meningococcal disease.
For example, tumour necrosis factor polymorphisms have been associated with susceptibility to malaria and other infections; chemokine receptor polymorphisms with susceptibility to HIV; natural resistance-associated macrophage protein 1 with tuberculosis; and mannose binding lectin polymorphisms with meningococcal disease.
The MBL pathway is a critical determinant of meningococcal-disease susceptibility, and genetic variants of MBL might account for a third of all disease cases.