Frontiers in Immunology (Aug 2019)
Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network
- Emilia Cirillo,
- Caterina Cancrini,
- Caterina Cancrini,
- Chiara Azzari,
- Silvana Martino,
- Baldassarre Martire,
- Andrea Pession,
- Alberto Tommasini,
- Samuele Naviglio,
- Andrea Finocchi,
- Andrea Finocchi,
- Rita Consolini,
- Paolo Pierani,
- Irene D'Alba,
- Maria Caterina Putti,
- Antonio Marzollo,
- Giuliana Giardino,
- Rosaria Prencipe,
- Federica Esposito,
- Fiorentino Grasso,
- Alessia Scarselli,
- Alessia Scarselli,
- Gigliola Di Matteo,
- Gigliola Di Matteo,
- Enrico Attardi,
- Silvia Ricci,
- Davide Montin,
- Fernando Specchia,
- Federica Barzaghi,
- Maria Pia Cicalese,
- Giuseppe Quaremba,
- Vassilios Lougaris,
- Silvia Giliani,
- Franco Locatelli,
- Paolo Rossi,
- Paolo Rossi,
- Alessandro Aiuti,
- Raffaele Badolato,
- Alessandro Plebani,
- Claudio Pignata
Affiliations
- Emilia Cirillo
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
- Caterina Cancrini
- Department of System of Medicine University of Rome Tor Vergata, Rome, Italy
- Caterina Cancrini
- Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, Italy
- Chiara Azzari
- Pediatric Immunology Unit, Anna Meyer Hospital, University of Florence, Florence, Italy
- Silvana Martino
- Department of Public Health and Pediatrics, Regina Margherita Children Hospital, University of Turin, Turin, Italy
- Baldassarre Martire
- Paediatric Hematology Oncology Unit, Policlinico-Giovanni XXII Hospital, University of Bari, Bari, Italy
- Andrea Pession
- Department of Pediatrics, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
- Alberto Tommasini
- Pediatric Hematology Oncology, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, Italy
- Samuele Naviglio
- Pediatric Hematology Oncology, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, Italy
- Andrea Finocchi
- Department of System of Medicine University of Rome Tor Vergata, Rome, Italy
- Andrea Finocchi
- Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, Italy
- Rita Consolini
- Section of Pediatrics Immunology and Rheumatology, Department of Pediatrics, University of Pisa, Pisa, Italy
- Paolo Pierani
- 0Division of Pediatric Hematology and Oncology, Ospedale G. Salesi, Ancona, Italy
- Irene D'Alba
- 0Division of Pediatric Hematology and Oncology, Ospedale G. Salesi, Ancona, Italy
- Maria Caterina Putti
- 1Department of Child's and Woman's Health, Pediatric Oncology and Hematology, University of Padova, Padova, Italy
- Antonio Marzollo
- 1Department of Child's and Woman's Health, Pediatric Oncology and Hematology, University of Padova, Padova, Italy
- Giuliana Giardino
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
- Rosaria Prencipe
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
- Federica Esposito
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
- Fiorentino Grasso
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
- Alessia Scarselli
- Department of System of Medicine University of Rome Tor Vergata, Rome, Italy
- Alessia Scarselli
- Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, Italy
- Gigliola Di Matteo
- Department of System of Medicine University of Rome Tor Vergata, Rome, Italy
- Gigliola Di Matteo
- Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, Italy
- Enrico Attardi
- Department of System of Medicine University of Rome Tor Vergata, Rome, Italy
- Silvia Ricci
- Pediatric Immunology Unit, Anna Meyer Hospital, University of Florence, Florence, Italy
- Davide Montin
- Department of Public Health and Pediatrics, Regina Margherita Children Hospital, University of Turin, Turin, Italy
- Fernando Specchia
- Department of Pediatrics, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
- Federica Barzaghi
- 2Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy
- Maria Pia Cicalese
- 2Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy
- Giuseppe Quaremba
- 3Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
- Vassilios Lougaris
- 4Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, University of Brescia, Brescia, Italy
- Silvia Giliani
- 5A. Nocivelli Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, and ASST Spedali Civili, Brescia, Italy
- Franco Locatelli
- 6Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Rome, Italy
- Paolo Rossi
- Department of System of Medicine University of Rome Tor Vergata, Rome, Italy
- Paolo Rossi
- Unit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, Italy
- Alessandro Aiuti
- 2Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy
- Raffaele Badolato
- 4Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, University of Brescia, Brescia, Italy
- Alessandro Plebani
- 4Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, University of Brescia, Brescia, Italy
- Claudio Pignata
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
- DOI
- https://doi.org/10.3389/fimmu.2019.01908
- Journal volume & issue
-
Vol. 10
Abstract
Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies. To this purpose, we conducted a 30-year retro-prospective multicenter study within the Italian Primary Immunodeficiency Network. One hundred eleven patients, diagnosed as typical or atypical SCID according to the European Society for Immune Deficiencies criteria, were included. Patients were subsequently classified based on the genetic alteration, pathogenic mechanism and immunological classification. A positive relationship between the age at onset and the DD was found. SCID patients with later onset were identified only in the last decade of observation. Syndromic SCIDs represented 28% of the cohort. Eight percent of the subjects were diagnosed in Intensive Care Units. Fifty-three percent had an atypical phenotype and most of them exhibited a discordant genotype-immunophenotype. Pre-treatment mortality was higher in atypical and syndromic patients. Our study broadens the knowledge of clinical and laboratory manifestations and genotype/phenotype correlation in patients with SCID and may facilitate the diagnosis of both typical and atypical forms of the disease in countries where newborn screening programs have not yet been implemented.
Keywords
- primary immunodeficiencies
- severe combined immunodeficiencies
- atypical SCID
- T-cell defects
- lymphopenia
- Omenn syndrome
