Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network
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 t...
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01908/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Emilia Cirillo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T13:15:58Z |
| format | Article |
| id | doaj.art-4a7c5098e4f1432ea68957c8c2668b7e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T13:15:58Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4a7c5098e4f1432ea68957c8c2668b7e2022-12-21T19:02:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-08-011010.3389/fimmu.2019.01908469175Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency NetworkEmilia Cirillo0Caterina Cancrini1Caterina Cancrini2Chiara Azzari3Silvana Martino4Baldassarre Martire5Andrea Pession6Alberto Tommasini7Samuele Naviglio8Andrea Finocchi9Andrea Finocchi10Rita Consolini11Paolo Pierani12Irene D'Alba13Maria Caterina Putti14Antonio Marzollo15Giuliana Giardino16Rosaria Prencipe17Federica Esposito18Fiorentino Grasso19Alessia Scarselli20Alessia Scarselli21Gigliola Di Matteo22Gigliola Di Matteo23Enrico Attardi24Silvia Ricci25Davide Montin26Fernando Specchia27Federica Barzaghi28Maria Pia Cicalese29Giuseppe Quaremba30Vassilios Lougaris31Silvia Giliani32Franco Locatelli33Paolo Rossi34Paolo Rossi35Alessandro Aiuti36Raffaele Badolato37Alessandro Plebani38Claudio Pignata39Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, ItalyDepartment of System of Medicine University of Rome Tor Vergata, Rome, ItalyUnit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, ItalyPediatric Immunology Unit, Anna Meyer Hospital, University of Florence, Florence, ItalyDepartment of Public Health and Pediatrics, Regina Margherita Children Hospital, University of Turin, Turin, ItalyPaediatric Hematology Oncology Unit, Policlinico-Giovanni XXII Hospital, University of Bari, Bari, ItalyDepartment of Pediatrics, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, ItalyPediatric Hematology Oncology, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, ItalyPediatric Hematology Oncology, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, ItalyDepartment of System of Medicine University of Rome Tor Vergata, Rome, ItalyUnit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, ItalySection of Pediatrics Immunology and Rheumatology, Department of Pediatrics, University of Pisa, Pisa, Italy0Division of Pediatric Hematology and Oncology, Ospedale G. Salesi, Ancona, Italy0Division of Pediatric Hematology and Oncology, Ospedale G. Salesi, Ancona, Italy1Department of Child's and Woman's Health, Pediatric Oncology and Hematology, University of Padova, Padova, Italy1Department of Child's and Woman's Health, Pediatric Oncology and Hematology, University of Padova, Padova, ItalyPediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, ItalyPediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, ItalyPediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, ItalyPediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, ItalyDepartment of System of Medicine University of Rome Tor Vergata, Rome, ItalyUnit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, ItalyDepartment of System of Medicine University of Rome Tor Vergata, Rome, ItalyUnit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, ItalyDepartment of System of Medicine University of Rome Tor Vergata, Rome, ItalyPediatric Immunology Unit, Anna Meyer Hospital, University of Florence, Florence, ItalyDepartment of Public Health and Pediatrics, Regina Margherita Children Hospital, University of Turin, Turin, ItalyDepartment of Pediatrics, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy2Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy2Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy3Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy4Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, University of Brescia, Brescia, Italy5A. Nocivelli Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, and ASST Spedali Civili, Brescia, Italy6Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Rome, ItalyDepartment of System of Medicine University of Rome Tor Vergata, Rome, ItalyUnit of Immune and Infectious Disease, University Department of Pediatrics DPUO, Children's Hospital Bambino Gesù, Rome, Italy2Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy4Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, University of Brescia, Brescia, Italy4Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, University of Brescia, Brescia, ItalyPediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, ItalySevere 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01908/fullprimary immunodeficienciessevere combined immunodeficienciesatypical SCIDT-cell defectslymphopeniaOmenn syndrome |
| spellingShingle | 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 Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network Frontiers in Immunology primary immunodeficiencies severe combined immunodeficiencies atypical SCID T-cell defects lymphopenia Omenn syndrome |
| title | Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network |
| title_full | Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network |
| title_fullStr | Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network |
| title_full_unstemmed | Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network |
| title_short | Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network |
| title_sort | clinical immunological and molecular features of typical and atypical severe combined immunodeficiency report of the italian primary immunodeficiency network |
| topic | primary immunodeficiencies severe combined immunodeficiencies atypical SCID T-cell defects lymphopenia Omenn syndrome |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01908/full |
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