SCIDS (Severe Combined Immunodeficient Syndrome)

The World Health Organization recognizes approximately 70 primary immune deficiencies including X-Linked Agammaglobulinemia, Common Variable Immune Deficiency (Hypogammaglobulinemia), Selective IgA Deficiency and Severe Combined Immune deficiency. SCID leads to severe Tand B-cell dysfunction. It is generally considered to be the most serious of the primary immunodeficiency diseases. Without intervention, death in children occurs by age 2 years.

• SCIDS X-Linked form:

  • -SCIDX

  Autosomal Recessive SCID (Swiss type Agammaglobulinemia):

  • -Janus Associated Kinase 3 Deficiency (JAK 3 Deficiency)

    Adenosine Deaminase Deficiency (ADA Deficiency)

    Purine Nucleoside Phosphorylase Deficiency (PNP Deficiency)

  Bare Lymphocyte Syndrome

  IL-2 Deficiency

  ZAP-70 Protein Tyrosine Kinase Deficiency (ZAP-70 PTK Deficiency)

  Reticular Dysgenesia

  Omenn Syndrome

1:100,000 live births. Higher incidence recently reported (1:50,000 to 1:75,000 live births), probably because of better identification of affected subjects.

Of all SCID cases, 50% are X-linked (gene mapped to Xq13) and 50% are various forms of autosomal recessive. Approximately 25% of the patients with an autosomal recessive SCID are Janus-associated kinase 3 (JAK3) deficient and 40% are adenosine deaminase (ADA) deficient. Gene mapped to 8q11, 5p13.

The pathophysiology and molecular biology vary according to the type of immunodeficiency. However, the lack of Tand B-cell function is the common endpoint in all forms of SCIDS.

X-Linked form: Mutation of the common gamma chain of the interleukin (IL-2R, IL-4R, IL-7R, IL-9R, IL-15R) resulting in loss of cytokine function. Loss of IL-2R function leads to the loss of a lymphocyte proliferation signal. Loss of IL-4R function leads to the inability of B cells to class switch. Loss of IL-7R function leads to the loss of an antiapoptotic signal, resulting in a loss of T-cell selection in the thymus. Loss of IL-7R function is also associated with the loss of a T-cell receptor (TCR) rearrangement. Loss of IL-15R function leads to the ablation of NK cell development. Lymphopenia occurs primarily from the absence of CD3+ and NK cells. Variable levels of B cells occur, which do not make functional antibodies.

Autosomal recessive SCID includes different types.

• Janus-Associated Kinase 3 (JAK3) Deficiency: JAK3 is a protein tyrosine kinase (PTK) that associates with the common gamma chain of the IL receptors. Lymphopenia occurs primarily from the absence of T cells (CD3+) and NK cells. Normal or high levels of B cells occur, which do not make functional antibodies.
• Adenosine Deaminase (ADA) Deficiency: Lymphopenia occurs from the death of T and B cells secondary to the accumulation of toxic metabolites in the purine salvage pathway. Functional antibodies are decreased or absent.
• Purine Nucleoside Phosphorylase (PNP) Deficiency: Same as ADA deficiency with circulating B cells normal in number. B-cell function is poor, as evidenced by the lack of antibody formation.
• Bare Lymphocyte Syndrome: This is a deficiency of major histocompatibility complex (MHC). The lymphocyte count is normal or mildly reduced, the CD4+ are decreased, and the CD8+ are normal or mildly increased. The B-cell ...