학술논문
Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network.
Document Type
Academic Journal
Author
Cirillo E; Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, via S. Pansini, 5-80131, Naples, Italy.; Polizzi A; Department of Educational Sciences, University of Catania, Catania, Italy.; Soresina A; Department of Clinical and Experimental Sciences, University of Brescia and Department of Pediatrics, ASST-Spedali Civili Di Brescia, Brescia, Italy.; Prencipe R; Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, via S. Pansini, 5-80131, Naples, Italy.; Giardino G; Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, via S. Pansini, 5-80131, Naples, Italy.; Cancrini C; Unit of Immunology and Infectious Diseases, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.; Finocchi A; Unit of Immunology and Infectious Diseases, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.; Rivalta B; Unit of Immunology and Infectious Diseases, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.; Dellepiane RM; Departments of Pediatrics, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.; Baselli LA; Departments of Pediatrics, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.; Montin D; Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics Regina Margherita Children Hospital, University of Turin, Turin, Italy.; Trizzino A; Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina and Benfratelli Hospital, Palermo, Italy.; Consolini R; Section of Pediatrics Immunology and Rheumatology, Department of Pediatrics, University of Pisa, Pisa, Italy.; Azzari C; Division of Pediatric Immunology, Department of Health Sciences, University of Florence and Meyer Children's Hospital, Florence, Italy.; Ricci S; Division of Pediatric Immunology, Department of Health Sciences, University of Florence and Meyer Children's Hospital, Florence, Italy.; Lodi L; Division of Pediatric Immunology, Department of Health Sciences, University of Florence and Meyer Children's Hospital, Florence, Italy.; Quinti I; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.; Milito C; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.; Leonardi L; Department of Pediatrics, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.; Duse M; Department of Pediatrics, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.; Carrabba M; Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Fabio G; Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Bertolini P; Pediatric Hematology Oncology Unit, Azienda Ospedaliero Universitaria of Parma, Parma, Italy.; Coccia P; Division of Pediatric Hematology and Oncology, Ospedale G. Salesi, Ancona, Italy.; D'Alba I; Division of Pediatric Hematology and Oncology, Ospedale G. Salesi, Ancona, Italy.; Pession A; Unit of Pediatrics, IRCCS Azienda Ospedaliero-Universitaria, Bologna, Italy.; Conti F; Unit of Pediatrics, IRCCS Azienda Ospedaliero-Universitaria, Bologna, Italy.; Zecca M; Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Lunardi C; Department of Medicine, University of Verona, Verona, Italy.; Bianco ML; Department of Educational Sciences, University of Catania, Catania, Italy.; Presti S; Department of Educational Sciences, University of Catania, Catania, Italy.; Sciuto L; Department of Educational Sciences, University of Catania, Catania, Italy.; Micheli R; Department of Clinical and Experimental Sciences, University of Brescia and Department of Pediatrics, ASST-Spedali Civili Di Brescia, Brescia, Italy.; Bruzzese D; Department of Public Health, Federico II University of Naples, Naples, Italy.; Lougaris V; Department of Clinical and Experimental Sciences, University of Brescia and Department of Pediatrics, ASST-Spedali Civili Di Brescia, Brescia, Italy.; Badolato R; Department of Clinical and Experimental Sciences, University of Brescia and Department of Pediatrics, ASST-Spedali Civili Di Brescia, Brescia, Italy.; Plebani A; Department of Clinical and Experimental Sciences, University of Brescia and Department of Pediatrics, ASST-Spedali Civili Di Brescia, Brescia, Italy.; Chessa L; Sapienza University Foundation, Roma, Italy.; Pignata C; Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, via S. Pansini, 5-80131, Naples, Italy. pignata@unina.it.
Source
Publisher: Springer Country of Publication: Netherlands NLM ID: 8102137 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2592 (Electronic) Linking ISSN: 02719142 NLM ISO Abbreviation: J Clin Immunol Subsets: MEDLINE
Subject
Language
English
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.
(© 2022. The Author(s).)
(© 2022. The Author(s).)