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Updated: Jun 10, 2026
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Published on: November 2, 2018
Inborn Errors of Immunity in the NF-κB Pathway
1Department of Pediatrics, National Defense Medical College, Saitama, Japan.
Summary
Novel mutations in the RELA gene cause immune disorders with increased type I interferon production. RelB deficiency leads to immunodeficiency and infections, linking NF-κB pathway defects to type I interferonopathies.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Inborn errors of immunity (IEIs) impacting the NF-κB pathway disrupt immune responses.
- IEIs can manifest with or without developmental abnormalities.
- Previous research linked RELA gene haploinsufficiency to specific immune issues.
Purpose of the Study:
- To investigate novel forms of IEIs.
- To explore the mechanistic link between NF-κB pathway defects and type I interferonopathies.
- To characterize RelB deficiency and its impact on immune function.
Main Methods:
- Analysis of patients with novel RELA mutations.
- Assessment of Toll-like receptor 7 (TLR7) and MYD88 mRNA expression in dendritic cells.
- Functional studies on patients with RelB deficiency and novel variants.
Main Results:
- Dominant-negative RELA mutations cause IEIs with increased TLR7-mediated type I interferon production.
- This links NF-κB pathway IEIs with type I interferonopathies.
- RelB deficiency disrupts the non-canonical NF-κB pathway, causing T- and B-cell immunodeficiency and autoantibodies against type I IFNs.
Conclusions:
- Novel RELA mutations represent a distinct class of IEIs.
- RelB deficiency causes severe immunodeficiency predisposing to infections.
- These findings bridge previously separate categories of IEIs.
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