Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network

Emilia Cirillo, Caterina Cancrini, Chiara Azzari, Silvana Martino, Baldassarre Martire, Andrea Pession, Alberto Tommasini, Samuele Naviglio, Andrea Finocchi, Rita Consolini, Paolo Pierani, Irene D'Alba, Maria Caterina Putti, Antonio Marzollo, Giuliana Giardino, Rosaria Prencipe, Federica Esposito, Fiorentino Grasso, Alessia Scarselli, Gigliola Di MatteoEnrico Attardi, Silvia Ricci, Davide Montin, Fernando Specchia, Federica Barzaghi, Maria Pia Cicalese, Giuseppe Quaremba, Vassilios Lougaris, Silvia Giliani, Franco Locatelli, Paolo Rossi, Alessandro Aiuti, Raffaele Badolato, Alessandro Plebani, Claudio Pignata

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1908
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 2019

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Severe Combined Immunodeficiency
Phenotype
Genetic Heterogeneity
Genetic Association Studies
Cell- and Tissue-Based Therapy
Hematopoietic Stem Cells
Age of Onset
Genetic Therapy
Multicenter Studies
Intensive Care Units
Atypical Severe combined immunodeficiency
Immune System
Genotype
Observation
Newborn Infant
Prospective Studies
Mortality
Infection

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Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency : Report of the Italian Primary Immunodeficiency Network. / Cirillo, Emilia; Cancrini, Caterina; Azzari, Chiara; Martino, Silvana; Martire, Baldassarre; Pession, Andrea; Tommasini, Alberto; Naviglio, Samuele; Finocchi, Andrea; Consolini, Rita; Pierani, Paolo; D'Alba, Irene; Putti, Maria Caterina; Marzollo, Antonio; Giardino, Giuliana; Prencipe, Rosaria; Esposito, Federica; Grasso, Fiorentino; Scarselli, Alessia; Di Matteo, Gigliola; Attardi, Enrico; Ricci, Silvia; Montin, Davide; Specchia, Fernando; Barzaghi, Federica; Cicalese, Maria Pia; Quaremba, Giuseppe; Lougaris, Vassilios; Giliani, Silvia; Locatelli, Franco; Rossi, Paolo; Aiuti, Alessandro; Badolato, Raffaele; Plebani, Alessandro; Pignata, Claudio.

In: Frontiers in Immunology, Vol. 10, 2019, p. 1908.

Research output: Contribution to journalArticle

Cirillo, E, Cancrini, C, Azzari, C, Martino, S, Martire, B, Pession, A, Tommasini, A, Naviglio, S, Finocchi, A, Consolini, R, Pierani, P, D'Alba, I, Putti, MC, Marzollo, A, Giardino, G, Prencipe, R, Esposito, F, Grasso, F, Scarselli, A, Di Matteo, G, Attardi, E, Ricci, S, Montin, D, Specchia, F, Barzaghi, F, Cicalese, MP, Quaremba, G, Lougaris, V, Giliani, S, Locatelli, F, Rossi, P, Aiuti, A, Badolato, R, Plebani, A & Pignata, C 2019, 'Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network', Frontiers in Immunology, vol. 10, pp. 1908. https://doi.org/10.3389/fimmu.2019.01908
Cirillo, Emilia ; Cancrini, Caterina ; Azzari, Chiara ; Martino, Silvana ; Martire, Baldassarre ; Pession, Andrea ; Tommasini, Alberto ; Naviglio, Samuele ; Finocchi, Andrea ; Consolini, Rita ; Pierani, Paolo ; D'Alba, Irene ; Putti, Maria Caterina ; Marzollo, Antonio ; Giardino, Giuliana ; Prencipe, Rosaria ; Esposito, Federica ; Grasso, Fiorentino ; Scarselli, Alessia ; Di Matteo, Gigliola ; Attardi, Enrico ; Ricci, Silvia ; Montin, Davide ; Specchia, Fernando ; Barzaghi, Federica ; Cicalese, Maria Pia ; Quaremba, Giuseppe ; Lougaris, Vassilios ; Giliani, Silvia ; Locatelli, Franco ; Rossi, Paolo ; Aiuti, Alessandro ; Badolato, Raffaele ; Plebani, Alessandro ; Pignata, Claudio. / Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency : Report of the Italian Primary Immunodeficiency Network. In: Frontiers in Immunology. 2019 ; Vol. 10. pp. 1908.
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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.",
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TY - JOUR

T1 - Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency

T2 - Report of the Italian Primary Immunodeficiency Network

AU - Cirillo, Emilia

AU - Cancrini, Caterina

AU - Azzari, Chiara

AU - Martino, Silvana

AU - Martire, Baldassarre

AU - Pession, Andrea

AU - Tommasini, Alberto

AU - Naviglio, Samuele

AU - Finocchi, Andrea

AU - Consolini, Rita

AU - Pierani, Paolo

AU - D'Alba, Irene

AU - Putti, Maria Caterina

AU - Marzollo, Antonio

AU - Giardino, Giuliana

AU - Prencipe, Rosaria

AU - Esposito, Federica

AU - Grasso, Fiorentino

AU - Scarselli, Alessia

AU - Di Matteo, Gigliola

AU - Attardi, Enrico

AU - Ricci, Silvia

AU - Montin, Davide

AU - Specchia, Fernando

AU - Barzaghi, Federica

AU - Cicalese, Maria Pia

AU - Quaremba, Giuseppe

AU - Lougaris, Vassilios

AU - Giliani, Silvia

AU - Locatelli, Franco

AU - Rossi, Paolo

AU - Aiuti, Alessandro

AU - Badolato, Raffaele

AU - Plebani, Alessandro

AU - Pignata, Claudio

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.3389/fimmu.2019.01908

DO - 10.3389/fimmu.2019.01908

M3 - Article

C2 - 31456805

VL - 10

SP - 1908

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -