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• W2079724632 abstract "Background: A deficiency in the interleukin-1 receptor activated kinase 4 (IRAK-4) has recently been associated with severe recurrent, predominantly Gram-positive bacterial infections. Clinical Presentation: Two unrelated Canadian children with unique presentations of IRAK-4 deficiency are described. Both children had multiple Gram-positive bacterial infections, specifically Staphylococcus aureus and Streptococcus pneumoniae. Although these microorganisms in patients with IRAK-4 deficiency commonly cause invasive infections, such as meningitis, arthritis, and sepsis, the sites of infection in our patients were unique. In the first patient, staphylococcal pericarditis and, on a separate occasion, staphylococcal liver abscesses with generalized peritonitis were presentations. In the second child, S. aureus infection caused submandibular and periauricular lymphadenitis with unsuspected paratracheal abscess as well. These severe infections were not accompanied by the expected constitutional symptoms or hematologic and acute phase responses despite findings of advanced infection on diagnostic imaging. Methods: Cytokine production [interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α] by whole blood leukocytes and adherent monocytes after stimulation with IL-1β or various Toll-like receptor agonists [lipopolysaccharide, Poly I:C, S. aureus peptidoglycan (PGN)] was analyzed. IRAK-4 genes were sequenced by standard techniques. Results: Failure by whole blood leukocytes to produce IL-6 or TNF-α in response to any of these stimuli was the most consistent finding. In striking contrast, IL-8 production in response to PGN was normal in both cases. Both patients had novel and heterozygous mutations and deletions in the IRAK-4 gene. Conclusions: Our results indicate that PGN-induced IL-6 production is via IRAK-4 dependent mechanisms, whereas IL-8 response to PGN is via IRAK-4 independent mechanisms. Patients with relatively silent but invasive bacterial infection should raise suspicion of IRAK-4 immunodeficiency." @default.
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• W2079724632 date "2008-02-01" @default.
• W2079724632 modified "2023-09-23" @default.
• W2079724632 title "Staphylococcal Pericarditis, and Liver and Paratracheal Abscesses as Presentations in Two New Cases of Interleukin-1 Receptor Associated Kinase 4 Deficiency" @default.
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• W2079724632 doi "https://doi.org/10.1097/inf.0b013e318157ad01" @default.
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