II. Epidemiology
- T-Cell Disorders account for 9-10% of Primary Immunodeficiency in both Europe and U.S.
III. Pathophysiology
- Most T-Cell Disorders are mixed T-Cell and B-Cell Disorders as B-Cells rely on T-Cells
- Contrast with Humoral Disorders which primarily affect B-Cells and Immunoglobulin
IV. Causes: Severe Combined Immunodeficiency (SCID)
- Severe T cell deficiency causes B Cell dysfunction
- X-Linked deficiency or Autosomal Recessive trait (1 in 100,000 live births in U.S.)
- Subtypes include X-Linked SCID, Autosomal Recessive SCID, Adenosine Deaminase Deficiency
- Onset before age 3 months
- Presents with Diarrhea, opportunistic infections, severe childhood infections and Failure to Thrive
- Specific infections include Otitis Media, Mononucleosis and Candidiasis
- Survival 90% with diagnosis and Stem Cell Transplant in first 3.5 months of life (contrast with 70% after that age)
- Added to routine Newborn Screening panels in about one third of U.S. States as of 2013-14
- False Positives 1.5% in term infants and 5% Preterm Infants in NICU (will requires re-testing)
V. Causes: Ataxia Telangiectasia
- Combined humoral and cell-mediated Immunity deficiency
- Impaired DNA repair mechanisms result in IgA deficiency (and possibly IgG2 and IgE deficiency)
- Onset of Telangiectasia by age 3-6 years old
- Progressive Ataxia affecting disordered ambulation by age 10-12 years old
- Recurrent sinus and lung infections, autoimmune disorders and malignancy (e.g. Non-Hodgkin Lymphoma)
VI. Causes: Wiscott-Aldrich Syndrome
- X-Linked disorder, typicalluy diagnosed around 21 months of age
- Classic triad of Thrombocytopenia, recurrent Otitis Media and Eczema (present in only 27% of cases)
- Thrombocytopenia with life threatening bleeding (GI Bleeding, Intracranial Bleeding) in up to 30% of children
VII. Causes: DiGeorge Syndrome (Velocardiofacial, Congenital Thymic Aplasia)
- Deletion at 22q11.2 results in incomplete development from third and fourth pharyngeal pouches
- Thymus hypoplasia
- Hypoparathyroidism with Hypocalcemia
- Cardiac abnormalities and altered facial features
- T Lymphocyte deficiency (low T-Cell numbers and decreased or absent T-Cell response)
- Severe Viral Infections from contagious spread or from Live Vaccine
- Persistent fungal infections (e.g. Thrush persists >12 months)
VIII. Resources
- National Primary Immunodeficiency Resource Center
- Immune Deficiency Foundation
IX. References
- Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL
- Cooper (2003) Am Fam Physician 68:2001-11 [PubMed]
- Reust (2013) Am Fam Physician 87(11): 773-8 [PubMed]
- Rosen (1995) N Engl J Med 333(7):431-440 [PubMed]