Clinical and Laboratory ObservationsInterleukin receptor–associated kinase (IRAK-4) deficiency associated with bacterial infections and failure to sustain antibody responses
Section snippets
Case report
This now 8-year-old girl, a product of father/daughter conception, was hospitalized repeatedly starting at 5 weeks of age for buccal cellulitis associated with severe thrush and Staphylococcus aureus bacteremia. She continues to have severe infections such as pneumonia, septicemia, bacterial arthritis, lymphadenitis, and pyelonephritis, requiring multiple hospitalizations for intravenous antimicrobial treatment (Table I). Organisms isolated included Gram-positive and Gram-negative bacteria,
Methods
The responses of patients' peripheral blood mononuclear cells to Toll-like receptor (TLR) ligands for the production of interleukin (IL)-6 was performed according to previously described methods.1., 2. IL-6 was determined by using the human IL-6 Quantikine ELISA Kit (R & D Systems, Minneapolis, Minn). Western blotting was carried out with the use of goat anti-MyD88 (myeloid differentiation factor 88) antibody, goat anti-IRAK-1 antibody, or goat anti–TRAF-6 (TNF receptor-associated factor 6)
Results
The patient's peripheral blood mononuclear cells, similar to the two other IRAK-4–deficient patients described previously,2 failed to produce IL-6 to all TLR ligands tested (heat-killed S aureus, triacylated lipopeptide, zymosan, peptideglycan, small antiviral peptide R848, CpG oligonucleotide). The patient's cells, however, were able to produce IL-6 after stimulation with pokeweed mitogen PMA plus ionomycin. Furthermore, the patient's fibroblasts exhibited impaired responses to IL-1β but not
Discussion
The three recently described patients with IRAK-4 deficiency2 had in common a history of frequent bacterial infections. Two of the patients gradually improved, and both have been well recently. The third, the young girl who is the subject of this report, has had recurring bacterial and fungal infections, eventually requiring IVIG therapy. Recently, a 23-year-old patient with a history of recurrent infections until 15 years of age and IRAK-4 deficiency was reported.6 Booster immunizations with
Acknowledgements
This article is dedicated to Robert A. Good, PhD, MD, who passed away June 13, 2003, and cared for the patient for 7 years.
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2022, Clinical Microbiology and InfectionCitation Excerpt :A 2010 study of >80 patients with IRAK-4 and MyD88 autosomal recessive deficiency presented a similar course, characterized by infectious susceptibility that was mainly limited to pyogenic bacteria in the form of sepsis, abscesses, cellulitis, arthritis, osteomyelitis, and meningitis, with generally no other severe infections [5,37,39,42–45]. These patients are characterized by the absence of fever or elevation of inflammatory markers despite severe infection and an unremarkable immunological characterization, except for reduced IgM memory B cells and unsustained vaccinal response [37,46,47]. Susceptibility to pyogenic infections has an early onset, usually by 2 years of life, gradually resolving during puberty, because no deaths and invasive infections have been recorded after the age of 8 and 14 years, respectively, even in the absence of therapeutic interventions [39,42].
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