T-Cell Deficiency Disorders, Inherited

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Recurrent infections, particularly with opportunistic organisms

Laboratory Testing

  • Initial testing
    • HIV testing
      • Infants ≤15 months – PCR qualitative or quantitative
      • Adults – screen for antibodies; confirm positive results with Western blot
    • CBC with differential – profound thrombocytopenia with small, nonfunctioning platelets suggests Wiskott-Aldrich syndrome
    • Immunoglobulin (quantitative) – if low, proceed with B-cell immunodeficiency testing
    • Sweat chloride – if positive, proceed with cystic fibrosis  genetic testing
    • T-cell immunodeficiency profile testing
      • T-cell testing at minimum should include CD4, CD45RA, CD45RO, CD8, CD4:8 ratio, CD3, CD19, and NK-cell
      • If abnormal, proceed with lymphocyte antigen and mitogen test
  • Cell-mediated immune screen – lymphocyte mitogen stimulated ATP production (LMPS); rapid overnight test
    • Lymphocyte antigen and mitogen proliferation test
      • Measures tritiated thymidine (3H-TdR) uptake by lymphocytes in response to stimulus (requires 5-7 days)
      • Low with low T-cells confirms T-cell disorder
    • Lymphocyte antigen and mitogen stimulation with cytokines
  • Further specific genetic testing based on the results of the above testing

Differential Diagnosis

Cell-mediated immunity is accomplished by T-lymphocytes (T-cells) and their effector response and interactions with other immune cells.

  • T-cell immunodeficiency diseases include
    • Severe combined immunodeficiencies (SCID)
    • Wiskott-Aldrich syndrome (WAS)
    • Ataxia telangiectasia
    • DiGeorge syndrome
    • Immuno-osseous dysplasias
    • Dyskeratosis congenta
    • Chronic mucocutaneous candidiasis


  • Incidence – rare (<1/1,000,000)
  • Age – most commonly discovered during neonatal period and infancy
    •  Adult onset rare
  • Sex – M:F, equal, except for X-linked diseases
    • M>F for X-linked SCID and WAS


  • Autosomal recessive for all diseases except X-linked SCID and WAS


  • Defective lymphocyte responses to stimulants may occur
    • Nonspecific mitogens (phytohemagglutinin, concanavalin A and pokeweed mitogen)
    • Specific antigens, such as Candida or tetanus
  • Characterized by increased susceptibility to infections from opportunistic organisms

Clinical Presentation

  • Ataxia telangiectasia
    • Recurrent infections – sinopulmonary are most common
    • Progressive cerebellar dysfunction
    • Oculocutaneous telangiectasia
    • Cancer risk 35-40% in affected individuals
      • Increased risk of solid tumors in older population
      • Leukemia and lymphoma in children
      • Risk ~4 times greater than general population, especially for breast cancer
  • Chronic mucocutaneous candidiasis
    • Persistent or recurrent Candida infections of the skin, nails and mucous membranes
    • Often have an associated autoimmune disease
    • May be associated with multiple endocrinopathies
  • DiGeorge syndrome
    • Recurrent infections – fungal, viral, bacterial, Pneumocystis
    • Congenital heart disease
    • Hypocalcemic tetany (due to hypoparathyroidism)
    • Abnormal facies
    • Palatal abnormalities
    • Thymic hypoplasia
  • SCID
    • Early onset of severe infections (intracellular bacterial, viral, fungal, Pneumocystis)
    • Growth failure
    • Persistent diarrhea
    • Graft-versus-host disease upon exposure to maternal lymphocytes or blood transfusions
    • Earliest onset in X-linked SCID, adenosine deaminase (ADA) deficiency, purine nucleoside phosphorylase deficiency (PNP), ZAP70 defects, and T- and B-cell variants
    • Refer to T- and B-cell Variants of SCID table in the SCID ARUP Consult topic
  • WAS
    • Recurrent infections – viral, pneumococcal
    • Eczema
    • Associated autoimmune disease common
    • Increased risk for malignancy
    • IgA nephropathy
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Human Immunodeficiency Virus 1 (HIV-1) by Qualitative PCR 0093061
Method: Qualitative Polymerase Chain Reaction

Human Immunodeficiency Virus 1 by Quantitative PCR 0055598
Method: Quantitative Polymerase Chain Reaction

Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies by CIA with Reflex to HIV-1 Antibody Confirmation by Western Blot 2005377
Method: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Immunoglobulins (IgA, IgG, IgM), Quantitative 0050630
Method: Quantitative Nephelometry


If results low, proceed to B-cell immunodeficiency testing

CD4+ T-Cell Recent Thymic Emigrants (RTEs) 2010179
Method: Quantitative Flow Cytometry

Lymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA and CD45RO 0095862
Method: Quantitative Flow Cytometry

Lymphocyte Subset Panel 7 - Congenital Immunodeficiencies 0095899
Method: Quantitative Flow Cytometry


Severe deficiencies in T cells should initiate differential workup based on deficiency

Lymphocyte Antigen and Mitogen Proliferation Panel 0096056
Method: Cell Culture


Bacterial or endotoxin contamination of sample profoundly affects test results


T-cell immunodeficiency profile (short and extended)

In addition, evaluate chronic infection based on clinical history and in conjunction with other tests

Natural Killer Cell and Natural Killer T-Cell Panel 2013805
Method: Semi-Quantitative Flow Cytometry

Natural Killer Cells Enumeration 0092404
Method: Quantitative Flow Cytometry

Chromosome Analysis - Breakage, Ataxia Telangiectasia, Whole Blood 2005749
Method: Giemsa Band


Carriers are not detected by this test


Al-Herz W, Bousfiha A, Casanova J, Chapel H, Conley ME, Cunningham-Rundles C, Etzioni A, Fischer A, Franco JL, Geha RS, Hammarström L, Nonoyama S, Notarangelo LD, Ochs HD, Puck JM, Roifman CM, Seger R, Tang ML. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2011; 2: 54. PubMed

General References

Filipovich A, Johnson J, Zhang K. WAS-Related Disorders. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews. University of Washington, 1993-2015. Seattle, WA [Last updated Mar 2014; Accessed: Nov 2015]

Gatti R. Ataxia-Telangiectasia. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Mar 2010; Accessed: Nov 2015]

Hershfield M. Adenosine Deaminase Deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Jun 2014; Accessed: Nov 2015]

Immune Deficiency Foundation. Towson, MD [Accessed: Feb 2017]

Kirkpatrick CH. Chronic mucocutaneous candidiasis. Pediatr Infect Dis J. 2001; 20(2): 197-206. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Augustine NH, Pasi BM, Hill HR. Comparison of ATP production in whole blood and lymphocyte proliferation in response to phytohemagglutinin. J Clin Lab Anal. 2007; 21(5): 265-70. PubMed

Efimova OV, Kelley TW. Induction of granzyme B expression in T-cell receptor/CD28-stimulated human regulatory T cells is suppressed by inhibitors of the PI3K-mTOR pathway. BMC Immunol. 2009; 10: 59. PubMed

Shyur SD, Hill HR. Immunodeficiency in the 1990s. Pediatr Infect Dis J. 1991; 10(8): 595-611. PubMed

Shyur SD, Hill HR. Recent advances in the genetics of primary immunodeficiency syndromes. J Pediatr. 1996; 129(1): 8-24. PubMed

Wang S, Delgado JC, Ravkov E, Eckels DD, Georgelas A, Pavlov IY, Cusick M, Sebastian K, Gleich GJ, Wagner LA. Penaeus monodon tropomyosin induces CD4 T-cell proliferation in shrimp-allergic patients. Hum Immunol. 2012; 73(4): 426-31. PubMed

Medical Reviewers

Last Update: July 2017