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

F Saettini; G Fazio; P Corti; M Quadri; C Bugarin; G Gaipa; F Penco; D Moratto; M Chiarini; M Baronio; L Gazzurelli; L Imberti; S Paghera; S Giliani; G Cazzaniga; A Plebani; R Badolato; V Lougaris; M Gattorno; A Biondi

doi:10.1016/j.clim.2020.108525

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.

Authors

F Saettini¹, G Fazio², P Corti³, M Quadri², C Bugarin², G Gaipa², F Penco⁴, D Moratto⁵, M Chiarini⁵, M Baronio⁶, L Gazzurelli⁶, L Imberti⁷, S Paghera⁷, S Giliani⁶, G Cazzaniga⁸, A Plebani⁶, R Badolato⁶, V Lougaris⁶, M Gattorno⁴, A Biondi⁹

Affiliations

¹ Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation, Monza, Italy. Electronic address: [email protected].
² Centro Ricerca Tettamanti, University of Milan Bicocca, Monza, Italy.
³ Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation, Monza, Italy.
⁴ Center for Autoinflammatory disease and Immunodeficiencies, IRCCS G. Gaslini, Genova, Italy.
⁵ Flow cytometry Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
⁶ Pediatrics Clinic and Institute of Molecular Medicine A. Novicelli, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy.
⁷ Centro di Ricerca Emato-oncologica AIL (CREA), ASST Spedali Civili, Brescia, Italy.
⁸ Centro Ricerca Tettamanti, University of Milan Bicocca, Monza, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy.
⁹ Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation, Monza, Italy; Centro Ricerca Tettamanti, University of Milan Bicocca, Monza, Italy.

PMID: 32659374
DOI: 10.1016/j.clim.2020.108525

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