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Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.
Fathi, Nazanin; Nirouei, Matineh; Salimian Rizi, Zahra; Fekrvand, Saba; Abolhassani, Hassan; Salami, Fereshte; Ketabforoush, Arsh Haj Mohamad Ebrahim; Azizi, Gholamreza; Saghazadeh, Amene; Esmaeili, Marzie; Almasi-Hashiani, Amir; Rezaei, Nima.
Afiliación
  • Fathi N; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Nirouei M; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
  • Salimian Rizi Z; Alborz University of Medical Sciences, Karaj, Iran.
  • Fekrvand S; Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • Abolhassani H; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Salami F; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
  • Ketabforoush AHME; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Azizi G; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  • Saghazadeh A; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Esmaeili M; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
  • Almasi-Hashiani A; Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
  • Rezaei N; Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
J Clin Immunol ; 44(7): 160, 2024 Jul 11.
Article en En | MEDLINE | ID: mdl-38990428
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Subunidad p50 de NF-kappa B / Subunidad p52 de NF-kappa B / Mutación Límite: Humans Idioma: En Revista: J Clin Immunol Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Subunidad p50 de NF-kappa B / Subunidad p52 de NF-kappa B / Mutación Límite: Humans Idioma: En Revista: J Clin Immunol Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Países Bajos