Cargando…

Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients

Activated phosphoinositide 3-kinase delta syndrome 1 (APDS-1) is a recently described inborn error of immunity caused by monoallelic gain-of-function mutations in the PIK3CD gene. We reviewed for the first time medical records and laboratory data of eight Italian APDS-1 patients. Recurrent sinopulmo...

Descripción completa

Detalles Bibliográficos
Autores principales: Tessarin, Giulio, Rossi, Stefano, Baronio, Manuela, Gazzurelli, Luisa, Colpani, Michael, Benvenuto, Alessio, Zunica, Fiammetta, Cardinale, Fabio, Martire, Baldassarre, Brescia, Letizia, Costagliola, Giorgio, Luti, Laura, Casazza, Gabriella, Menconi, Maria Cristina, Saettini, Francesco, Palumbo, Laura, Girelli, Maria Federica, Badolato, Raffaele, Lanzi, Gaetana, Chiarini, Marco, Moratto, Daniele, Meini, Antonella, Giliani, Silvia, Bondioni, Maria Pia, Plebani, Alessandro, Lougaris, Vassilios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603210/
https://www.ncbi.nlm.nih.gov/pubmed/33080915
http://dx.doi.org/10.3390/jcm9103335
_version_ 1783603870812864512
author Tessarin, Giulio
Rossi, Stefano
Baronio, Manuela
Gazzurelli, Luisa
Colpani, Michael
Benvenuto, Alessio
Zunica, Fiammetta
Cardinale, Fabio
Martire, Baldassarre
Brescia, Letizia
Costagliola, Giorgio
Luti, Laura
Casazza, Gabriella
Menconi, Maria Cristina
Saettini, Francesco
Palumbo, Laura
Girelli, Maria Federica
Badolato, Raffaele
Lanzi, Gaetana
Chiarini, Marco
Moratto, Daniele
Meini, Antonella
Giliani, Silvia
Bondioni, Maria Pia
Plebani, Alessandro
Lougaris, Vassilios
author_facet Tessarin, Giulio
Rossi, Stefano
Baronio, Manuela
Gazzurelli, Luisa
Colpani, Michael
Benvenuto, Alessio
Zunica, Fiammetta
Cardinale, Fabio
Martire, Baldassarre
Brescia, Letizia
Costagliola, Giorgio
Luti, Laura
Casazza, Gabriella
Menconi, Maria Cristina
Saettini, Francesco
Palumbo, Laura
Girelli, Maria Federica
Badolato, Raffaele
Lanzi, Gaetana
Chiarini, Marco
Moratto, Daniele
Meini, Antonella
Giliani, Silvia
Bondioni, Maria Pia
Plebani, Alessandro
Lougaris, Vassilios
author_sort Tessarin, Giulio
collection PubMed
description Activated phosphoinositide 3-kinase delta syndrome 1 (APDS-1) is a recently described inborn error of immunity caused by monoallelic gain-of-function mutations in the PIK3CD gene. We reviewed for the first time medical records and laboratory data of eight Italian APDS-1 patients. Recurrent sinopulmonary infections were the most common clinical feature at onset of disease. Seven patients presented lymphoproliferative disease, at onset or during follow-up, one of which resembled hemophagocytic lymphohistiocytosis (HLH). Genetic analysis of the PIK3CD gene revealed three novel mutations: functional testing confirmed their activating nature. In the remaining patients, the previously reported variants p.E1021K (n = 4) and p.E525A (n = 1) were identified. Six patients were started on immunoglobulin replacement treatment (IgRT). One patient successfully underwent hematopoietic stem cell transplantation (HSCT), with good chimerism and no GVHD at 21 months post-HSCT. APDS-1 is a combined immune deficiency with a wide variety of clinical manifestations and a complex immunological presentation. Besides IgRT, specific therapies targeting the PI3Kδ pathway will most likely become a valid aid for the amelioration of patients’ clinical management and their quality of life.
format Online
Article
Text
id pubmed-7603210
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76032102020-11-01 Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients Tessarin, Giulio Rossi, Stefano Baronio, Manuela Gazzurelli, Luisa Colpani, Michael Benvenuto, Alessio Zunica, Fiammetta Cardinale, Fabio Martire, Baldassarre Brescia, Letizia Costagliola, Giorgio Luti, Laura Casazza, Gabriella Menconi, Maria Cristina Saettini, Francesco Palumbo, Laura Girelli, Maria Federica Badolato, Raffaele Lanzi, Gaetana Chiarini, Marco Moratto, Daniele Meini, Antonella Giliani, Silvia Bondioni, Maria Pia Plebani, Alessandro Lougaris, Vassilios J Clin Med Article Activated phosphoinositide 3-kinase delta syndrome 1 (APDS-1) is a recently described inborn error of immunity caused by monoallelic gain-of-function mutations in the PIK3CD gene. We reviewed for the first time medical records and laboratory data of eight Italian APDS-1 patients. Recurrent sinopulmonary infections were the most common clinical feature at onset of disease. Seven patients presented lymphoproliferative disease, at onset or during follow-up, one of which resembled hemophagocytic lymphohistiocytosis (HLH). Genetic analysis of the PIK3CD gene revealed three novel mutations: functional testing confirmed their activating nature. In the remaining patients, the previously reported variants p.E1021K (n = 4) and p.E525A (n = 1) were identified. Six patients were started on immunoglobulin replacement treatment (IgRT). One patient successfully underwent hematopoietic stem cell transplantation (HSCT), with good chimerism and no GVHD at 21 months post-HSCT. APDS-1 is a combined immune deficiency with a wide variety of clinical manifestations and a complex immunological presentation. Besides IgRT, specific therapies targeting the PI3Kδ pathway will most likely become a valid aid for the amelioration of patients’ clinical management and their quality of life. MDPI 2020-10-17 /pmc/articles/PMC7603210/ /pubmed/33080915 http://dx.doi.org/10.3390/jcm9103335 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tessarin, Giulio
Rossi, Stefano
Baronio, Manuela
Gazzurelli, Luisa
Colpani, Michael
Benvenuto, Alessio
Zunica, Fiammetta
Cardinale, Fabio
Martire, Baldassarre
Brescia, Letizia
Costagliola, Giorgio
Luti, Laura
Casazza, Gabriella
Menconi, Maria Cristina
Saettini, Francesco
Palumbo, Laura
Girelli, Maria Federica
Badolato, Raffaele
Lanzi, Gaetana
Chiarini, Marco
Moratto, Daniele
Meini, Antonella
Giliani, Silvia
Bondioni, Maria Pia
Plebani, Alessandro
Lougaris, Vassilios
Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients
title Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients
title_full Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients
title_fullStr Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients
title_full_unstemmed Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients
title_short Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients
title_sort activated phosphoinositide 3-kinase delta syndrome 1: clinical and immunological data from an italian cohort of patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603210/
https://www.ncbi.nlm.nih.gov/pubmed/33080915
http://dx.doi.org/10.3390/jcm9103335
work_keys_str_mv AT tessaringiulio activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT rossistefano activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT baroniomanuela activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT gazzurelliluisa activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT colpanimichael activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT benvenutoalessio activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT zunicafiammetta activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT cardinalefabio activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT martirebaldassarre activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT brescialetizia activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT costagliolagiorgio activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT lutilaura activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT casazzagabriella activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT menconimariacristina activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT saettinifrancesco activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT palumbolaura activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT girellimariafederica activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT badolatoraffaele activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT lanzigaetana activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT chiarinimarco activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT morattodaniele activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT meiniantonella activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT gilianisilvia activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT bondionimariapia activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT plebanialessandro activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients
AT lougarisvassilios activatedphosphoinositide3kinasedeltasyndrome1clinicalandimmunologicaldatafromanitaliancohortofpatients