Clinical, Immunological, and Molecular Findings in Four Cases of B Cell Expansion With NF-κB and T Cell Anergy Disease for the First Time From India

Front Immunol. 2018 Jun 14:9:1049. doi: 10.3389/fimmu.2018.01049. eCollection 2018.

Abstract

B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by mutations in the CARD11 gene and results in constitutive NF-κB activation in B and T cells. Affected patients present with polyclonal expansion of B cells at an early age with splenomegaly, lymphadenopathy, and mild autoimmunity. Here, we discuss four BENTA cases with unusual clinical manifestations not previously reported. All patients showed previously reported gain-of-function mutations (G123S, G123D, and C49Y) in the CARD11 gene. Severe autoimmune manifestations were noted for the first time in all our patients.

Keywords: CARD11; GOF mutation; NF-κB; autoimmune lymphoproliferative syndrome; polyclonal B cell lymphocytosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Lymphoproliferative Syndrome / diagnosis
  • Autoimmune Lymphoproliferative Syndrome / genetics*
  • B-Lymphocytes / cytology*
  • CARD Signaling Adaptor Proteins / genetics*
  • Child, Preschool
  • Clonal Anergy*
  • Female
  • Gain of Function Mutation
  • Guanylate Cyclase / genetics*
  • Humans
  • India
  • Infant
  • Male
  • NF-kappa B / metabolism*
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / pathology*
  • Whole Genome Sequencing

Substances

  • CARD Signaling Adaptor Proteins
  • NF-kappa B
  • CARD11 protein, human
  • Guanylate Cyclase