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IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation
- Source :
- Journal of clinical immunology.
- Publication Year :
- 2022
-
Abstract
- Abstract 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.
- Subjects :
- Science & Technology
DE-NOVO-MECP2 DUPLICATION
CLINICAL-FEATURES
Immunology
FUNCTIONAL DISOMY
Xq28 Duplication syndrome
Inborn errors of immunity
INCLUDING MECP2
Methyl CpG binding protein 2 (MECP2)
MENTAL-RETARDATION SYNDROME
INHERITED DUPLICATION
GENE DUPLICATION
Methyl CpG binding protein 2 (MECP2) duplication syndrome
COPY-NUMBER
X-CHROMOSOME
Canonical NF-kappa B signaling
EPILEPTIC SPASMS
Immunology and Allergy
Interleukin-1 receptor-associated kinase 1 (IRAK1)
Life Sciences & Biomedicine
Subjects
Details
- ISSN :
- 15732592
- Database :
- OpenAIRE
- Journal :
- Journal of clinical immunology
- Accession number :
- edsair.doi.dedup.....20418c2d2fd6daf8c030b2b842624de3