Cell Types Affected in Severe Combined Immunodeficiency (SCID)
In a child diagnosed with Severe Combined Immunodeficiency (SCID), T cells are always affected, with variable involvement of B cells and NK cells depending on the specific genetic defect. 1
Primary Cell Types Affected in SCID
T cells: Always affected in SCID, with very low or absent autologous T-cell counts and profoundly reduced proliferation to mitogens and antigens. This is the hallmark immunologic abnormality of SCID. 1
B cells: Often functionally impaired, though numbers may be normal or reduced depending on the specific genetic defect. Hypogammaglobulinemia results from both lack of T-cell help and intrinsic B-cell abnormalities. 1
NK cells: May be normal or reduced depending on the specific genetic defect. Some forms of SCID affect T, B, and NK cells (e.g., gamma chain and JAK3 deficiencies), while others primarily affect T cells or T and B cells. 1, 2
Cell Types Not Primarily Affected in SCID
Neutrophils: Not primarily affected in classic SCID. The only exception is reticular dysgenesis, an extremely rare form of SCID that also affects neutrophil development. 1
Eosinophils: Not primarily affected in SCID. 1
Diagnostic Patterns in SCID
Different genetic forms of SCID present with distinctive patterns of immune cell abnormalities:
T-B-NK- phenotype: Seen in adenosine deaminase (ADA) deficiency, which causes the most profound lymphopenia affecting all lymphocyte lineages. 1, 2
T-B+NK- phenotype: Common in X-linked SCID (gamma chain deficiency) and JAK3 deficiency, characterized by the most B cells and fewest NK cells. 1, 2
T-B-NK+ phenotype: Seen in RAG1/2 deficiencies and other defects in V(D)J recombination. 1
T-B+NK+ phenotype: Observed in IL-7 receptor deficiency and CD3 complex defects. 1
Laboratory Findings in SCID
Complete blood count typically reveals leukopenia and lymphopenia. 1
Immunoglobulin levels show low or absent IgA and IgM with variable IgG levels (IgG may be normal due to maternal transfer). 1
Flow cytometry demonstrates severely reduced or absent T cells, with variable B and NK cell numbers. 1
T-cell function tests show profoundly reduced proliferation to mitogens and antigens. 1
Newborn screening using T-cell receptor excision circles (TRECs) can identify SCID early, as infants with SCID have very low or absent TRECs. 1
Clinical Implications
The specific pattern of affected cells helps determine the underlying genetic defect and guides treatment approaches. 1, 2
All forms of SCID require urgent intervention, as they are fatal within the first year of life without treatment. 3, 4
Hematopoietic stem cell transplantation (HSCT) is the definitive treatment for most forms of SCID, with better outcomes when performed early. 1, 5
Gene therapy and enzyme replacement therapy are available for specific forms of SCID. 3, 5