Staphylococcal Pericarditis, and Liver and Paratracheal Abscesses as Presentations in Two New Cases of Interleukin-1 Receptor Associated Kinase 4 Deficiency
Bibliographic record
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)-alpha] by whole blood leukocytes and adherent monocytes after stimulation with IL-1beta 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-alpha 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".