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

. 2022 Mar 8.
 doi: 10.1007/s10875-022-01234-4. Online ahead of print.

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

Emilia Cirillo#1, Agata Polizzi#2, Annarosa Soresina3, Rosaria Prencipe1, Giuliana Giardino1, Caterina Cancrini4, Andrea Finocchi4, Beatrice Rivalta4, Rosa M Dellepiane5, Lucia A Baselli5, Davide Montin6, Antonino Trizzino7, Rita Consolini8, Chiara Azzari9, Silvia Ricci9, Lorenzo Lodi9, Isabella Quinti10, Cinzia Milito10, Lucia Leonardi11, Marzia Duse11, Maria Carrabba12, Giovanna Fabio12, Patrizia Bertolini13, Paola Coccia14, Irene D'Alba14, Andrea Pession15, Francesca Conti15, Marco Zecca16, Claudio Lunardi17, Manuela Lo Bianco2, Santiago Presti2, Laura Sciuto2, Roberto Micheli3, Dario Bruzzese18, Vassilios Lougaris3, Raffaele Badolato3, Alessandro Plebani3, Luciana Chessa#19, Claudio Pignata#pignata@unina.it.">20
Affiliations 

Affiliations

  • 1Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, via S. Pansini, 5-80131, Naples, Italy.
  • 2Department of Educational Sciences, University of Catania, Catania, Italy.
  • 3Department of Clinical and Experimental Sciences, University of Brescia and Department of Pediatrics, ASST-Spedali Civili Di Brescia, Brescia, Italy.
  • 4Unit of Immunology and Infectious Diseases, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.
  • 5Departments of Pediatrics, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.
  • 6Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics Regina Margherita Children Hospital, University of Turin, Turin, Italy.
  • 7Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina and Benfratelli Hospital, Palermo, Italy.
  • 8Section of Pediatrics Immunology and Rheumatology, Department of Pediatrics, University of Pisa, Pisa, Italy.
  • 9Division of Pediatric Immunology, Department of Health Sciences, University of Florence and Meyer Children's Hospital, Florence, Italy.
  • 10Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • 11Department of Pediatrics, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
  • 12Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  • 13Pediatric Hematology Oncology Unit, Azienda Ospedaliero Universitaria of Parma, Parma, Italy.
  • 14Division of Pediatric Hematology and Oncology, Ospedale G. Salesi, Ancona, Italy.
  • 15Unit of Pediatrics, IRCCS Azienda Ospedaliero-Universitaria, Bologna, Italy.
  • 16Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • 17Department of Medicine, University of Verona, Verona, Italy.
  • 18Department of Public Health, Federico II University of Naples, Naples, Italy.
  • 19Sapienza University Foundation, Roma, Italy.
  • 20Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, via S. Pansini, 5-80131, Naples, Italy. pignata@unina.it.
#Contributed equally.
    • PMID: 35257272
 

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.

Keywords: Ataxia telangiectasia; B lymphocytes; T lymphocytes; genotype; lymphopenia; primary immunodeficiency.