Journal of Clinical Medicine (Oct 2020)
Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients
- Giulio Tessarin,
- Stefano Rossi,
- Manuela Baronio,
- Luisa Gazzurelli,
- Michael Colpani,
- Alessio Benvenuto,
- Fiammetta Zunica,
- Fabio Cardinale,
- Baldassarre Martire,
- Letizia Brescia,
- Giorgio Costagliola,
- Laura Luti,
- Gabriella Casazza,
- Maria Cristina Menconi,
- Francesco Saettini,
- Laura Palumbo,
- Maria Federica Girelli,
- Raffaele Badolato,
- Gaetana Lanzi,
- Marco Chiarini,
- Daniele Moratto,
- Antonella Meini,
- Silvia Giliani,
- Maria Pia Bondioni,
- Alessandro Plebani,
- Vassilios Lougaris
Affiliations
- Giulio Tessarin
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Stefano Rossi
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Manuela Baronio
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Luisa Gazzurelli
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Michael Colpani
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Alessio Benvenuto
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Fiammetta Zunica
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Fabio Cardinale
- Allergy, Immunology and Pediatric Pulmonology Unit, “Policlinico-Giovanni XXII” Hospital, University of Bari, 70126 Bari, Italy
- Baldassarre Martire
- Pediatrics Unit, Monsignor Dimiccoli Hospital, 70051 Barletta, Italy
- Letizia Brescia
- Pediatric Oncohematology Unit, Ospedale Santissima Annunziata, 74121 Taranto, Italy
- Giorgio Costagliola
- Division of Pediatrics, University of Pisa, 56126 Pisa, Italy
- Laura Luti
- Pediatric Oncology and Hematology, University of Pisa, 56126 Pisa, Italy
- Gabriella Casazza
- Pediatric Oncology and Hematology, University of Pisa, 56126 Pisa, Italy
- Maria Cristina Menconi
- Pediatric Oncology and Hematology, University of Pisa, 56126 Pisa, Italy
- Francesco Saettini
- Pediatric Hematology Oncology Unit, Department of Pediatrics, University of Milano Bicocca, MBBM Foundation, 20900 Monza, Italy
- Laura Palumbo
- Pediatrics Clinic, ASST-Spedali Civili of Brescia, 25123 Brescia, Italy
- Maria Federica Girelli
- Pediatrics Clinic, ASST-Spedali Civili of Brescia, 25123 Brescia, Italy
- Raffaele Badolato
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Gaetana Lanzi
- “Angelo Nocivelli” Institute for Molecular Medicine, ASST Spedali Civili, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
- Marco Chiarini
- Clinical Chemical Analysis Central Laboratory, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Daniele Moratto
- Clinical Chemical Analysis Central Laboratory, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Antonella Meini
- Pediatrics Clinic, ASST-Spedali Civili of Brescia, 25123 Brescia, Italy
- Silvia Giliani
- Cytogenetic and Medical Genetics Unit and “A. Nocivelli” Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Maria Pia Bondioni
- Pediatric Radiology, University of Brescia, ASST Spedali Civili di Brescia, 25123 Brescia, Italy
- Alessandro Plebani
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- Vassilios Lougaris
- Pediatrics Clinic and “A. Nocivelli” Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
- DOI
- https://doi.org/10.3390/jcm9103335
- Journal volume & issue
-
Vol. 9,
no. 10
p. 3335
Abstract
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.
Keywords
- activated phosphoinositide 3-kinase delta syndrome 1
- lymphoproliferation
- primary combined immune deficiency
- p110δ
- <i>PIK3CD</i>
- PI3K