Two siblings presenting with novel ADA2 variants, lymphoproliferation, persistence of large granular lymphocytes, and T-cell perturbations

Clin Immunol. 2020 Sep:218:108525. doi: 10.1016/j.clim.2020.108525. Epub 2020 Jul 11.

Abstract

The presence of large granular lymphocytes has been reported in patients with ADA2 deficiency and T-LGL leukemia. Here we describe two siblings with novel ADA2 variants, expanding the mutational spectrum of ADA2 deficiency. We show that lymphoproliferation, persistence of large granular lymphocytes, T-cell perturbations, and activation of PI3K pathway, measured by means of phosphorylation levels of S6, are detectable in DADA2 patients without T-LGL leukemia.

Keywords: ADA2 deficiency; DADA2; Hypogammaglobulinemia; Large granular lymphocytes; Lymphopenia; Lymphoproliferation; T-cell repertoire.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • Adenosine Deaminase / deficiency*
  • Adenosine Deaminase / genetics*
  • Child
  • Genetic Variation
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology*
  • Intercellular Signaling Peptides and Proteins / deficiency*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lymphocytes / immunology*
  • Male
  • Siblings

Substances

  • Intercellular Signaling Peptides and Proteins
  • ADA2 protein, human
  • Adenosine Deaminase