Severe combined immunodeficiency

Severe combined immunodeficiency 

Updated: 08/07/2024

© Jun Wang, MD, PhD

General features
  • Heterogeneous group
  • Variable genetic abnormalities
  • T-cell defects with associated B-cell dysfunction
  • May develop non-Hodgkin lymphoma
  • Death may occur within first year of life unless stem cell transplantation
Clinical presentations
  • Usually have positive family history
  • Presentation shortly after birth
  • Severe and often life threatening infections
  • Opportunistic infections
  • Failure to thrive
  • Mucocutaneous candidiasis resistant to treatment
  • Autoimmune disorders
Genetic abnormalities and associated pathogenesis
  • X-linked: most common type, mutations of common gamma-chain of interleukin receptors, causing defective lymphocytic proliferative (IL-2), B-cell class switch (IL-4), T-cell selection in thymus (IL-7), and NK-cell development (IL-15)
  • Autosomal recessive: mutation of adenosine deaminase, etc, causing accumulation of cytotoxic DNA byproducts (Deoxy-ATP, etc) and subsequent inhibition of lymphocytic proliferation and increased apoptosis
  • Recombinase-activating genes: defects of T-cell receptor rearrangement and immunoglobulin formation
  • JAK3: common gamma-chain of interleukin receptor
  • ZAP70: T cell selection in thymus
Key Laboratory findings
  • Lymphocytopenia, especially T cells
  • Absence of both mature T and B cells 20% of patients
  • B-cell population may be normal or increased in X-linked SCID
  • Low immunoglobulin levels, especially IgM
  • Low T cell receptor excision circles (TREC)
Key morphological features
  • Small or absent thymus
  • Underdeveloped lymphoid tissue
  • Markedly depleted T-cell and/or underdeveloped B-cell areas
Newborn Screening
  • Universal in the States since 2010
  • Detect T cell receptor excision circles (TRECs)
  • SCID patients have low or no TRECs
Managements
  • Stem cell transplantation
  • Gene therapy


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