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.
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.