Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency

Abstract

Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background, clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities.

Fig. 1

Chest radiograph from a 5-month-old infant with severe combined immunodeficiency showing bilateral patchy shadowing secondary to interstitial pnuemonitis due to infection with respiratory syncytial virus and Pneumocystis jiroveci. There is hyperinflation of the lungs, and the midline pleural borders of the upper lobes are visible because the thymic shadow is absent (courtesy of The Paediatric Immunology Unit, Great North Children’s Hospital, Newcastle upon Tyne)

Fig. 2

A newborn infant with Omenn’s syndrome due to a mutation in the RAG 1 gene. Note the confluent erythematous exfoliating, thickened rash with a “leathery” consistency and loss of hair and eyebrows (courtesy of The Paediatric Immunology Unit, Great North Children’s Hospital, Newcastle upon Tyne)

Fig. 3

Flow cytometric analysis of peripheral blood and bone marrow of SCID patients. a Flow cytometric analysis of lymphocyte subsets in peripheral blood of SCID patients can be used for definition of the type of SCID and guides molecular diagnostics. b For B− SCID patients, flow cytometric analysis of the bone marrow precursor B cell compartment delineates the precursor B cell differentiation block, which can be helpful in candidate gene selection

Fig. 4

a γc/JAK3 signalling pathway (adapted from Gaspar et al. [23]). b T cell receptor with CD3 signalling complex

Fig. 5

A schematic representation of the three steps of the V(D)J recombination process and the involved molecules

Fig. 6

Distribution of B+ SCID (n = 159 patients) and B− SCID (n = 136 patients) in Europe according to the ESID patient registry 2010 (http://www.esid.org/statistics.php?sub=2). ESID, European Society for Immunodeficiencies