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Severe combined immunodeficiencies and related disorders

Nature Reviews Disease Primers volume 1, Article number: 15061 (2015) Cite this article

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Abstract

Severe combined immunodeficiencies (SCIDs) comprise a group of rare, monogenic diseases that are characterized by an early onset and a profound block in the development of T lymphocytes. Given that adaptive immunity is abrogated, patients with SCID are prone to recurrent infections caused by both non-opportunistic and opportunistic pathogens, leading to early death unless immunity can be restored. Several molecular defects causing SCIDs have been identified, along with many other defects causing profound, albeit incomplete, T cell immunodeficiencies; the latter are referred to as atypical SCIDs or combined immunodeficiencies. The pathophysiology of many of these conditions has now been characterized. Early, accurate and precise diagnosis combined with the ongoing implementation of newborn screening have enabled major advances in the care of infants with SCID, including better outcomes of allogeneic haematopoietic stem cell transplantation. Gene therapy is also becoming an effective option. Further advances and a progressive extension of the indications for gene therapy can be expected in the future. The assessment of long-term outcomes of patients with SCID is now a major challenge, with a view to evaluating the quality and sustainability of immune restoration, the risks of sequelae and the ability to relieve the non-haematopoietic syndromic manifestations that accompany some of these conditions.

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Figure 1: Lymphocyte differentiation and primary immunodeficiencies.
Figure 2: Proportions of SCID genotypes diagnosed with or without newborn screening.
Figure 3: A schematic view of blocks in lymphocyte differentiation causing SCIDs.
Figure 4: V(D)J rearrangements.
Figure 5: Defects of T cell signalling associated with primary immunodeficiency.
Figure 6: Overview of gene therapy for SCIDs.

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Authors and Affiliations

  1. Paris Descartes — Sorbonne Paris Cité University, Imagine Institute, Paris, 75015, France

    Alain Fischer, Bénédicte Neven & Marina Cavazzana

  2. Immunology and Pediatric Hematology Department, Assistance Publique-Hôpitaux de Paris, Paris, France

    Alain Fischer & Bénédicte Neven

  3. INSERM UMR, Paris, 1163, France

    Alain Fischer, Bénédicte Neven & Marina Cavazzana

  4. Collège de France, Paris, France

    Alain Fischer

  5. Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Luigi D. Notarangelo

  6. Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

    Marina Cavazzana

  7. Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France

    Marina Cavazzana

  8. Division of Allergy, Department of Pediatrics, Immunology and Blood and Marrow Transplantation, University of California at San Francisco, San Francisco, California, USA

    Jennifer M. Puck

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  1. Alain Fischer
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  2. Luigi D. Notarangelo
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  3. Bénédicte Neven
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  4. Marina Cavazzana
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Contributions

Introduction (A.F.); Epidemiology (J.M.P.); Mechanisms/pathophysiology (A.F. and L.D.N.); Diagnosis, screening and prevention (J.M.P.); Management (M.C.); Quality of life (B.N.); Outlook (A.F.); Overview of Primer (A.F.).

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Correspondence to Alain Fischer.

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Fischer, A., Notarangelo, L., Neven, B. et al. Severe combined immunodeficiencies and related disorders. Nat Rev Dis Primers 1, 15061 (2015). https://doi.org/10.1038/nrdp.2015.61

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