Severe Combined Immunodeficiencies

Severe combined immune deficiencies (SCIDs) represent a heterogeneous group of inherited disorders characterized by severe impairment of T and/or B cell development. The clinical presentation can be relatively uniform, including life-threatening infections and failure to thrive, and is associated in many cases with a broad spectrum of clinical manifestations, including inflammation, autoimmunity, and lymphoproliferative diseases. Because of the severity of the clinical manifestations, SCID is a pediatric emergency which, if not recognized early, can be fatal. Genetic studies and recent advances in genome sequencing have greatly unraveled the molecular basis of SCID and in parallel have highlighted the role played by various genes in the differentiation of T and B cells. Furthermore, compelling evidence has demonstrated the complex molecular heterogeneity underlying similar immunophenotypes, and in other cases has shown that defects in the same molecule might result in different clinical manifestations. Overall, these findings highlight the relevance of genetic studies and suggest the use of molecular and immunological studies as a comprehensive approach to rapid diagnosis of immunodeficiency.In this chapter are described the clinical and immunological phenotypes and recent insights into the pathophysiology of clinical manifestations of immune dysregulation associated with immunodeficiency.