Immune

Cell-Mediated Immunodeficiency

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Cell-Mediated Immunodeficiency, Cell Mediated Immunity Disorder, T-Cell Disorder, Severe Combined Immunodeficiency, SCID, Ataxia Telangiectasia, Wiscott-Aldrich Syndrome, DiGeorge Syndrome, Velocardiofacial Syndrome, Congenital Thymic Aplasia

  • Epidemiology
  1. T-Cell Disorders account for 9-10% of Primary Immunodeficiency in both Europe and U.S.
  • Pathophysiology
  1. Most T-Cell Disorders are mixed T-Cell and B-Cell Disorders as B-Cells rely on T-Cells
  2. Contrast with Humoral Disorders which primarily affect B-Cells and Immunoglobulin
  • Causes
  • Severe Combined Immunodeficiency (SCID)
  1. Severe T cell deficiency causes B Cell dysfunction
  2. X-Linked deficiency or Autosomal Recessive trait (1 in 100,000 live births in U.S.)
  3. Subtypes include X-Linked SCID, Autosomal Recessive SCID, Adenosine Deaminase Deficiency
  4. Onset before age 3 months
  5. Presents with Diarrhea, opportunistic infections, severe childhood infections and Failure to Thrive
  6. Specific infections include Otitis Media, Mononucleosis and Candidiasis
  7. Survival 90% with diagnosis and Stem Cell Transplant in first 3.5 months of life (contrast with 70% after that age)
    1. Added to routine Newborn Screening panels in about one third of U.S. States as of 2013-14
    2. False Positives 1.5% in term infants and 5% Preterm Infants in NICU (will requires re-testing)
  • Causes
  • Ataxia Telangiectasia
  1. Combined humoral and cell-mediated Immunity deficiency
  2. Impaired DNA repair mechanisms result in IgA deficiency (and possibly IgG2 and IgE deficiency)
  3. Onset of telangiectasia by age 3-6 years old
  4. Progressive Ataxia affecting disordered ambulation by age 10-12 years old
  5. Recurrent sinus and lung infections, autoimmune disorders and malignancy (e.g. Non-Hodgkin Lymphoma)
  • Causes
  • Wiscott-Aldrich Syndrome
  1. X-Linked disorder, typicalluy diagnosed around 21 months of age
  2. Classic triad of Thrombocytopenia, recurrent Otitis Media and Eczema (present in only 27% of cases)
  3. Thrombocytopenia with life threatening bleeding (GI Bleeding, Intracranial Bleeding) in up to 30% of children
  • Causes
  • DiGeorge Syndrome (Velocardiofacial, Congenital Thymic Aplasia)
  1. Deletion at 22q11.2 results in incomplete development from third and fourth pharyngeal pouches
    1. Thymus hypoplasia
    2. Hypoparathyroidism with Hypocalcemia
    3. Cardiac abnormalities and altered facial features
  2. T Lymphocyte deficiency (low T-Cell numbers and decreased or absent T-Cell response)
    1. Severe Viral Infections from contagious spread or from Live Vaccine
    2. Persistent fungal infections (e.g. Thrush persists >12 months)
  • Resources
  1. National Primary Immunodeficiency Resource Center
    1. http://npi.jmfworld.org
  2. Immune Deficiency Foundation
    1. http://www.primaryimmune.org