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Review
. 2023 Mar;19(3):329-339.
doi: 10.1080/1744666X.2023.2174105. Epub 2023 Feb 9.

How do nuclear factor kappa B (NF-κB)1 and NF-κB2 defects lead to the incidence of clinical and immunological manifestations of inborn errors of immunity?

Nazanin Fathi  1   2 , Hanieh Mojtahedi  2   3 , Marzieh Nasiri  1 , Hassan Abolhassani  1   4 , Mahsa Yousefpour Marzbali  1   5 , Marzie Esmaeili  1   2 , Fereshte Salami  1   2 , Furozan Biglari  6 , Nima Rezaei  1   2   7
Affiliations
Review

How do nuclear factor kappa B (NF-κB)1 and NF-κB2 defects lead to the incidence of clinical and immunological manifestations of inborn errors of immunity?

Nazanin Fathi et al. Expert Rev Clin Immunol. 2023 Mar.

Abstract

Introduction: Genetic defects affect the manner of the immune system's development, activation, and function. Nuclear factor-kappa B subunit 1 (NF-κB1) and NF-κB2 are involved in different biological processes, and deficiency in these transcription factors may reveal clinical and immunological difficulties.

Areas covered: This review article gathers the most frequent clinical and immunological remarkable characteristics of NF-κB1 and NF-κB2 deficiencies. Afterward, an effort is made to describe the biological mechanism, which is likely to be the cause of these clinical and immunological abnormalities.

Expert opinion: The present review article has explained the mechanism of contributions of the NF-κB1 and NF-κB2 deficiency in revealing immunodeficiency symptoms, specifically immunological and clinical manifestations. These mechanisms demonstrate the importance of NF-κB1 and NF-κB2 signaling pathways for B and T cell development, activation, antibody production, and immunotolerance. The manifestation of a mutation can range from no symptoms to severe complications in a family.

Keywords: Antibody deficiency; NF-κB1; NF-κB2; common variable immunodeficiency; inborn errors of immunity; nuclear factor kappa B; primary immunodeficiency.

Plain language summary

NF-κB1 and NF-κB2 are the transcription factors that have an essential role in the development and function of the immune system. Several mutations in the NF-κBs could lead to inborn errors of immune manifestations.There are different reports of NF-κB mutations with various clinical and immunological manifestations, whereas the mechanisms behind the appearance of these have been less discussed. We collected frequent clinical and immunological manifestations from the literature and discussed the likely biological cause of their occurrence. Here we clarify the potential mechanism that defects in NF-κB1 and NF-κB2 signaling lead to inadequate B and T cells function, specifically, insufficient switched memory B cells and class-switched antibodies and autoimmunity. We also focused on the straight correlation between deficiencies in immune system responses caused by defects in NF-κB and susceptibility to recurrent infections and other clinical problems.Since our understanding of the mechanisms of signaling pathways such as NF-κB deficiencies from genetic mutations to clinical manifestations in PIDs is limited, further in vitro and animal model studies are necessary to assess these pathways’ comprehensive roles in immunodeficiency more accurately. [Figure: see text].

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