| Autor: |
Gottschalk, Ilona, Kölsch, Uwe, Wagner, Dimitrios L., Kath, Jonas, Martini, Stefania, Krüger, Renate, Puel, Anne, Casanova, Jean-Laurent, Jezela-Stanek, Aleksandra, Rossi, Rainer, Chehadeh, Salima El, Van Esch, Hilde, von Bernuth, Horst |
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| Zdroj: |
Journal of Clinical Immunology; Feb2023, Vol. 43 Issue 2, p421-439, 19p |
| Abstrakt: |
Purpose: Besides their developmental and neurological phenotype, most patients with MECP2/IRAK1 duplication syndrome present with recurrent and severe infections, accompanied by strong inflammation. Respiratory infections are the most common cause of death. Standardized pneumological diagnostics, targeted anti-infectious treatment, and knowledge of the underlying pathomechanism that triggers strong inflammation are unmet clinical needs. We investigated the influence of IRAK1 overexpression on the canonical NF-κB signaling as a possible cause for excessive inflammation in these patients. Methods: NF-κB signaling was examined by measuring the production of proinflammatory cytokines and evaluating the IRAK1 phosphorylation and degradation as well as the IκBα degradation upon stimulation with IL-1β and TLR agonists in SV40-immortalized fibroblasts, PBMCs, and whole blood of 9 patients with MECP2/IRAK1 duplication syndrome, respectively. Results: Both, MECP2/IRAK1-duplicated patients and healthy controls, showed similar production of IL-6 and IL-8 upon activation with IL-1β and TLR2/6 agonists in immortalized fibroblasts. In PBMCs and whole blood, both patients and controls had a similar response of cytokine production after stimulation with IL-1β and TLR4/2/6 agonists. Patients and controls had equivalent patterns of IRAK1 phosphorylation and degradation as well as IκBα degradation upon stimulation with IL-1β. Conclusion: Patients with MECP2/IRAK1 duplication syndrome do not show increased canonical NF-κB signaling in immortalized fibroblasts, PBMCs, and whole blood. Therefore, we assume that these patients do not benefit from a therapeutic suppression of this pathway. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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