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Open Access 08-03-2022 | Primary Immunodeficiency | Original Article

Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network

Authors: Emilia Cirillo, Agata Polizzi, Annarosa Soresina, Rosaria Prencipe, Giuliana Giardino, Caterina Cancrini, Andrea Finocchi, Beatrice Rivalta, Rosa M. Dellepiane, Lucia A. Baselli, Davide Montin, Antonino Trizzino, Rita Consolini, Chiara Azzari, Silvia Ricci, Lorenzo Lodi, Isabella Quinti, Cinzia Milito, Lucia Leonardi, Marzia Duse, Maria Carrabba, Giovanna Fabio, Patrizia Bertolini, Paola Coccia, Irene D’Alba, Andrea Pession, Francesca Conti, Marco Zecca, Claudio Lunardi, Manuela Lo Bianco, Santiago Presti, Laura Sciuto, Roberto Micheli, Dario Bruzzese, Vassilios Lougaris, Raffaele Badolato, Alessandro Plebani, Luciana Chessa, Claudio Pignata

Published in: Journal of Clinical Immunology | Issue 4/2022

Abstract

Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype–phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects.

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Title: Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network
Authors: Emilia Cirillo
Agata Polizzi
Annarosa Soresina
Rosaria Prencipe
Giuliana Giardino
Caterina Cancrini
Andrea Finocchi
Beatrice Rivalta
Rosa M. Dellepiane
Lucia A. Baselli
Davide Montin
Antonino Trizzino
Rita Consolini
Chiara Azzari
Silvia Ricci
Lorenzo Lodi
Isabella Quinti
Cinzia Milito
Lucia Leonardi
Marzia Duse
Maria Carrabba
Giovanna Fabio
Patrizia Bertolini
Paola Coccia
Irene D’Alba
Andrea Pession
Francesca Conti
Marco Zecca
Claudio Lunardi
Manuela Lo Bianco
Santiago Presti
Laura Sciuto
Roberto Micheli
Dario Bruzzese
Vassilios Lougaris
Raffaele Badolato
Alessandro Plebani
Luciana Chessa
Claudio Pignata
Publication date: 08-03-2022
Publisher: Springer US
Keywords: Primary Immunodeficiency
Ataxia Telangiectasia
Lymphopenia
Published in: Journal of Clinical Immunology / Issue 4/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-022-01234-4

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