EDA-ID and IP, Two Faces of the Same Coin: How the Same IKBKG / NEMO Mutation Affecting the NF-B Pathway Can Cause Immunodeficiency and/or Inflammation

Francesca Fusco, Alessandra Pescatore, Matilde Immacolata Conte, Peppino Mirabelli, Mariateresa Paciolla, Elio Esposito, Maria Brigida Lioi, Matilde Valeria Ursini

Research output: Contribution to journalArticle

Abstract

Anhidrotic Ectodermal Dysplasia with ImmunoDeficiency (EDA-ID, OMIM 300291) and Incontinentia Pigmenti (IP, OMIM 308300) are two rare diseases, caused by mutations of the IKBKG/NEMO gene. The protein NEMO/IKKγ is essential for the NF-B activation pathway, involved in a variety of physiological and cellular processes, such as immunity, inflammation, cell proliferation, and survival.A wide spectrum of IKBKG/NEMO mutations have been identified so far, and, on the basis of their effect on NF-B activation, they are considered hypomorphic or amorphic (loss of function) mutations. IKBKG/NEMO hypomorphic mutations, reducing but not abolishing NF-B activation, have been identified in EDA-ID and IP patients. Instead, the amorphic mutations, abolishing NF-B activation by complete IKBKG/NEMO gene silencing, cause only IP.Here, we present an overview of IKBKG/NEMO mutations in EDA-ID and IP patients and describe similarities and differences between the clinical/immunophenotypic and genetic aspects, highlighting any T and B lymphocyte defect, and paying particular attention to the cellular and molecular defects that underlie the pathogenesis of both diseases.

Original languageEnglish
Pages (from-to)445-459
Number of pages15
JournalInternational Reviews of Immunology
Volume34
Issue number6
DOIs
Publication statusPublished - Nov 2 2015

    Fingerprint

Keywords

  • IKBKG/NEMO mutations
  • immunodeficiency
  • inflammation
  • mutation sequence analysis
  • NF-κB

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this