AUTHOR=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 TITLE=Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01908 DOI=10.3389/fimmu.2019.01908 ISSN=1664-3224 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.