T-Cell Deficiency Disorders, Inherited

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, non-functioning platelets suggests Wiskott-Aldrich syndrome
- Total absolute lymphocyte count
- Immunoglobulin quantitative – if low, proceed with B-cell immunodeficiency testing
- Sweat chloride – if positive, proceed with cystic fibrosis genetic testing
Cell-mediated immune screen – lymphocyte mitogen stimulated ATP production (LMPS); rapid overnight test
- Lymphocyte subset – if low, proceed with lymphocyte antigen and mitogen 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 the following

Adenosine deaminase deficiency
Ataxia telangiectasia
Chronic mucocutaneous candidiasis
DiGeorge syndrome
Purine nucleoside phosphorylase deficiency
Severe combined immunodeficiencies (SCID)
Wiskott-Aldrich syndrome (WAS)

Epidemiology

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

Inheritance

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

Pathophysiology

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 four 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
- 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

Treatment

Patients with severe T-cell defects, such as SCID, may be appropriate candidates for bone marrow or stem cell transplants and possibly gene therapy
Evaluation in the first 2-3 months of life treatment may decrease morbidity and mortality

Tests generally appear in the order most useful for common clinical situations

Test name: Human Immunodeficiency Virus 1, PCR, Qualitative

ARUP #: 0093061

Methodology: Qualitative Polymerase Chain Reaction

Use:

Initial testing for infants less than or equal to 15 months

Qualitative screen for presence of HIV-1 infection

Test name: Human Immunodeficiency Virus 1 RNA Quantitative Real-Time PCR

ARUP #: 0055598

Methodology: Quantitative Real-Time Polymerase Chain Reaction

Use:

Initial testing for infants less than or equal to 15 months

Quantitative screen for presence of HIV-1 infection

Test name: Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies with Reflex to Human Immunodeficiency Virus Type 1 (HIV-1) Antibody Confirmation by Western Blot

ARUP #: 2005377

Methodology: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

Use:

Initial testing for adults

Screen for antibodies against HIV-1 and HIV-2

If test is repeatedly reactive, confirmation will be made by Western Blot

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Initial testing

Assess for thrombocytopenia

Test name: Immunoglobulins (IgA, IgG, IgM), Quantitative

ARUP #: 0050630

Methodology: Quantitative Nephelometry

Use: Initial testing

Follow-up:

If results low, proceed to B-cell immunodeficiency testing

Test name: Lymphocyte Subset Panel 7 - Congenital Immunodeficiencies

ARUP #: 0095899

Methodology: Quantitative Flow Cytometry

Use:

Initial testing

Aid in diagnosis of T-cell deficiency

Limitations:

Time sensitive

Follow-up:

If results low, proceed to lymphocyte antigen & mitogen proliferation testing

Test name: Lymphocyte Antigen & Mitogen Proliferation Panel

ARUP #: 0096056

Methodology: Cell Culture

Use:

Test for lymphocyte proliferation in response to the following

Phytohemagglutinin
Concanavalin A
Pokeweed mitogen
Candida antigen
Tetanus antigens

Use to evaluate T-cell mediated immune deficiency

Limitations:

Bacterial or endotoxin contamination of sample profoundly affects test results

Follow-up:

T-cell immunodeficiency profile (short and extended)

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

Test name: Cell-Mediated Immune Function Screen

ARUP #: 0051273

Methodology: Cell Culture/Quantitative Chemiluminescence

Use:

Rapid screen for suspected cell-mediated immune dysfunction

Limitations:

Assay does not directly quantify level of immunosuppression

Test name: Chromosome Analysis - Breakage, Ataxia Telangiectasia, Whole Blood

ARUP #: 2005749

Methodology: Giemsa-Band and Special Stain Analysis

Use:

Detect ataxia telangiectasia

Limitations:

Carriers are not detected by this test

Additional Tests Available

Test name: Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response to Mitogens, 12 Cytokines

ARUP #: 0051584

Methodology: Cell Culture/Multi-Analyte Fluorescence Detection

Comments:

Test for lymphocyte cytokine responses to:

Phytohemagglutinin
Concanavalin A
Pokeweed mitogen
Candida antigen
Tetanus antigens

Use to evaluate chronic infections

Test name: Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response to Mitogens, Monokines

ARUP #: 0051587

Methodology: Cell Culture/Multi-Analyte Fluorescence Detection

Comments:

Test name: Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response to Mitogens, TH2 Cytokines

ARUP #: 0051586

Methodology: Cell Culture/Multi-Analyte Fluorescence Detection

Comments:

Test name: Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response to Mitogens, TH1 Cytokines

ARUP #: 0051585

Methodology: Cell Culture/Multi-Analyte Fluorescence Detection

Comments:

Test name: Lymphocyte Antigen Proliferation

ARUP #: 0096055

Methodology: Cell Culture

Comments:

Rapid test for Candida and tetanus antigens

Use to evaluate chronic infections

General

ARUP Institute for Clinical and Experimental Pathology®

Comprehensive Review: December 2011
Last Update: December 2011

Bruton Agammaglobulinemia

Chronic Granulomatous Disease

Common Variable Immune Deficiency

Complement Deficiency

Human Immunodeficiency Virus

Immunodeficiency, Innate System

Immunoglobulin Disorders

Leukocyte Adhesion Deficiency

Neutrophil Disorders

Severe Combined Immunodeficiencies