Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review
- 01.10.2024
- Review
Erschienen in:
- Verfasst von
- Nazanin Fathi
- Matineh Nirouei
- Zahra Salimian Rizi
- Saba Fekrvand
- Hassan Abolhassani
- Fereshte Salami
- Arsh Haj Mohamad Ebrahim Ketabforoush
- Gholamreza Azizi
- Amene Saghazadeh
- Marzie Esmaeili
- Amir Almasi-Hashiani
- Nima Rezaei
- Erschienen in
- Journal of Clinical Immunology | Ausgabe 7/2024
Abstract
Background
Inborn errors of immunity (IEIs) encompass various diseases with diverse clinical and immunological symptoms. Determining the genotype–phenotype of different variants in IEI entity precisely is challenging, as manifestations can be heterogeneous even in patients with the same mutated gene.
Objective
In the present study, we conducted a systematic review of patients recorded with NFKB1 and NFKB2 mutations, two of the most frequent monogenic IEIs.
Methods
The search for relevant literature was conducted in databases including Web of Science, PubMed, and Scopus. Information encompassing demographic, clinical, immunological, and genetic data was extracted from cases reported with mutations in NFKB1 and NFKB2. The comprehensive features of manifestations in patients were described, and a comparative analysis of primary characteristics was conducted between individuals with NFKB1 loss of function (LOF) and NFKB2 (p52-LOF/IκBδ-gain of function (GOF)) variants.
Results
A total of 397 patients were included in this study, 257 had NFKB1 mutations and 140 had NFKB2 mutations. There were 175 LOF cases in NFKB1 and 122 p52LOF/IκBδGOF cases in NFKB2 pivotal groups with confirmed functional implications. NFKB1LOF and p52LOF/IκBδGOF predominant cases (81.8% and 62.5% respectively) initially presented with a CVID-like phenotype. Patients with NFKB1LOF variants often experienced hematologic autoimmune disorders, whereas p52LOF/IκBδGOF patients were more susceptible to other autoimmune diseases. Viral infections were markedly higher in p52LOF/IκBδGOF cases compared to NFKB1LOF (P-value < 0.001). NFKB2 (p52LOF/IκBδGOF) patients exhibited a greater prevalence of ectodermal dysplasia and pituitary gland involvement than NFKB1LOF patients. Most NFKB1LOF and p52LOF/IκBδGOF cases showed low CD19 + B cells, with p52LOF/IκBδGOF having more cases of this type. Low memory B cells were more common in p52LOF/IκBδGOF patients.
Conclusions
Patients with NFKB2 mutations, particularly p52LOF/IκBδGOF, are at higher risk of viral infections, pituitary gland involvement, and ectodermal dysplasia compared to patients with NFKB1LOF mutations. Genetic testing is essential to resolve the initial complexity and confusion surrounding clinical and immunological features. Emphasizing the significance of functional assays in determining the probability of correlations between mutations and immunological and clinical characteristics of patients is crucial.
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- Titel
- Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review
- Verfasst von
-
Nazanin Fathi
Matineh Nirouei
Zahra Salimian Rizi
Saba Fekrvand
Hassan Abolhassani
Fereshte Salami
Arsh Haj Mohamad Ebrahim Ketabforoush
Gholamreza Azizi
Amene Saghazadeh
Marzie Esmaeili
Amir Almasi-Hashiani
Nima Rezaei
- Publikationsdatum
- 01.10.2024
- Verlag
- Springer US
- Erschienen in
-
Journal of Clinical Immunology / Ausgabe 7/2024
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592 - DOI
- https://doi.org/10.1007/s10875-024-01763-0
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