Background: About 2% of childhood episodes of invasive pneumococcal disease (IPD) are recurrent, and most remain unexplained.
Objective: To report two cases of otherwise healthy, unrelated children with recurrent IPD as the only clinical infectious manifestation of an inherited disorder in nuclear factor-κB(NF-κB)-dependent immunity.
Results: One child carried two germline mutations in IRAK4, and had impaired cellular responses to interleukin (IL)1 receptor and toll-like receptor (TLR) stimulation. The other child carried a hemizygous mutation in NEMO, associated with a broader impairment of NF-κB activation, with an impaired cellular response to IL-1R, TLR and tumour necrosis factor receptor stimulation. The two patients shared a narrow clinical phenotype, associated with two related but different genotypes.
Conclusions: Otherwise healthy children with recurrent IPD should be explored for underlying primary immunodeficiencies affecting the IRAK4-dependent and NEMO-dependent signalling pathways.
- CRP, C reactive protein
- EDA, ectodermal dysplasia
- IPD, invasive pneumococcal disese
- PCR, polymerase chain reaction
- PID, primary immunodeficiency
- PMN, polymorphonuclear neutrophil
- RT-PCR, reverse transcription PCR
- TLR, toll like receptor
- TNF, tumour necrosis factor
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
Published Online First 1 September 2006
↵* Current address: Laboratory of Dendritic Cells Immunobiology, Institut Pasteur, Paris, France.
↵† These authors contributed equally to this study.
Funding: The Laboratory of Human Genetics of Infectious Diseases is supported in part by grants from the Schlumberger and BNP Paribas Foundations, the Deutsche Forschungsgemeinschaft (VO 995-1/1) and EU grant QLK2-CT-2002-00846. Grants from the Hungarian Research Fund (OTKA T 038095 and OTKA T 049017) and the European Commission (EURO-PID-NAS QLQ1-CT-2001-01395) to LM supported this work.
Competing interests: XB is a senior clinical investigator of the Fund for Scientific Research—Flanders. J-LC is an International Scholar of the Howard Hughes Medical Institute.