Mutations in IRAK4 selectively impair TLRs other than TLR3 and most IL-1R responses, and confer a predisposition to pyogenic bacterial diseases, including invasive pneumococcal disease in particular.
Otherwise healthy children with recurrent IPD should be explored for underlying primary immunodeficiencies affecting the IRAK4-dependent and NEMO-dependent signalling pathways.
Our findings suggest that rare, functional variants in MYD88, IRAK4 or IKBKG do not significantly contribute to IPD susceptibility in adults at the population level.