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Test ID GLICP CD8 T-Cell Immune Competence Panel, Global

Reporting Name

CD8 Immune Competence Panel

Useful For

Determining over immunosuppression within the CD8 T-cell compartment, when used on transplant recipients and patients with autoimmune disorders receiving therapy with immunosuppressant agents

Profile Information

Test ID Reporting Name Available Separately Always Performed
TBBS QN Lymphocyte Subsets: T, B, and NK Yes Yes
GLIC CD8 Immune Competence, B Yes Yes

Specimen Type

WB Sodium Heparin
Whole Blood EDTA


Shipping Instructions


Specimens are required to be received in the laboratory weekdays and by 4 p.m. on Friday. It is recommended that specimens arrive within 24 hours of draw. Samples arriving on the weekend may be canceled. Draw and package specimen as close to shipping time as possible. Ship specimen overnight in an Ambient Mailer-Critical Specimens Only (T668).



Necessary Information


Date of draw is required.



Specimen Required


For serial monitoring, we recommend that specimen draws be performed at the same time of day.

 

Two separate specimens are required.

 

Specimen Type: EDTA whole blood

Container/Tube: 4 mL Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Send specimen in original tube. Do not aliquot.

2. Label specimen as blood for TBBS / Quantitative Lymphocyte Subsets: T, B, and NK.

 

Specimen Type: Sodium heparin whole blood

Container/Tube: Green top (sodium heparin)

Specimen Volume: 15 mL

Collection Instructions: Label specimen as blood for GLIC / CD8 T-Cell Immune Competence, Global, Blood.


Specimen Minimum Volume

CD8 Immune Competence: 10 mL; Quantitative Lymphocyte Subsets: 1 mL

Specimen Stability Information

Specimen Type Temperature Time
WB Sodium Heparin Ambient 48 hours
Whole Blood EDTA Ambient 52 hours

Reference Values

The appropriate age-related reference values will be provided on the report.

Day(s) and Time(s) Performed

Monday through Friday

Specimens are required to be received in the lab weekdays and by 4 p.m. on Friday. No weekend processing.

Test Classification

See Individual Test IDs

CPT Code Information

QN Lymphocyte Subsets: T, B, and NK

86355-B cells, total count

86357-Natural killer (NK) cells, total count

86359-T cells, total count

86360-Absolute CD4/CD8 count with ratio

 

CD8 T-Cell Immune Competence, Global, Blood

86356 x 2

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GLICP CD8 Immune Competence Panel In Process

 

Result ID Test Result Name Result LOINC Value
30643 IFN-g In Process
3321 CD45 Total Lymph Count 27071-0
30644 CD107a/b In Process
3316 % CD3 (T Cells) 8124-0
30645 Interpretation 69052-9
3322 CD3 (T Cells) 8122-4
3319 % CD4 (T Cells) 8123-2
3325 CD4 (T Cells) 24467-3
3320 % CD8 (T Cells) 8101-8
3326 CD8 (T Cells) 14135-8
3318 % CD19 (B Cells) 8117-4
3324 CD19 (B Cells) 8116-6
4054 % CD16+CD56 (NK cells) 8112-5
4055 CD16+CD56 (NK cells) 20402-4
3327 4/8 Ratio 54218-3
6657 Comment 48767-8

Clinical Information

CD8 T cells play an important role in the immune response to viral or intracellular infectious agents, as well as antitumor immunity and immune surveillance.

 

Upon activation, CD8 T cells mediate a variety of effector functions, including cytokine secretion and cytotoxicity. Interferon-gamma (IFN-gamma) is one of the early cytokines produced by CD8 T cells; it is released within a few hours of activation.(1) The cytotoxic function is mediated by the contents of the cytolytic granules.(1) Cell-surface mobilization of the cytolytic granule components, CD107a and CD107b, also known as lysosome-associated membrane proteins LAMP-1 and LAMP-2, occurs when CD8 T cells mediate their cytolytic function and degranulate.(2)

 

CD8 T-cell activation occurs either through the T cell receptor peptide major histocompatibility complex (MHC) or by use of a mitogen (eg, phorbol myristate acetate and the calcium ionophore ionomycin). Mitogen-mediated activation is antigen nonspecific.

 

Impairment of global CD8 T-cell activation (due to inherent cellular immunodeficiency or as a consequence of over-immunosuppression by therapeutic agents) results in reduced production of IFN-gamma and other cytokines, reduced cytotoxic function, and increased risk for developing infectious complications. Agents associated with over-immunosuppression include the calcineurin inhibitors (eg, cyclosporine A, FK506 [Prograf/tacrolimus], and rapamycin [sirolimus]), antimetabolites (eg, mycophenolate mofetil), and thymoglobulin.

 

Immunosuppression is most commonly used for allograft maintenance in solid-organ transplant recipients, to prevent graft-versus-host disease in allogeneic hematopoietic stem cell transplant patients and, to treat patients with autoimmune diseases. In these settings, reducing the risk for developing infectious complications as a result of over-immunosuppression is a clinical challenge.

 

Therapeutic drug monitoring is routinely used in the transplant practice to avoid overtreatment and to determine patient compliance. But, the levels of drugs measured in blood do not directly correlate with the administered dose due to individual pharmacokinetic differences.(3) Furthermore, drug levels may not necessarily correlate with biological activity of the drug. Consequently, it may be beneficial to consider modification of the immunosuppression regimen based on the patient's level of functional immune competence.

 

This assay provides a means to evaluate over-immunosuppression within the CD8 T-cell compartment (global CD8 T-cell function). Intracellular IFN-gamma expression is a marker for CD8 T-cell activation. Surface CD107a and CD107b are markers for cytotoxic function. This test may be most useful when ordered at the end of induction immunosuppression and 2 to 3 months after maintenance immunosuppression to ensure that global CD8 T-cell function is not compromised. The test may also provide value when immunosuppression is increased to halt or prevent graft rejection, to provide information on a balance between over-immunosuppression with subsequent infectious comorbidities and, under-immunosuppression with resultant graft rejection.

 

The absolute counts of lymphocyte subsets are known to be influenced by a variety of biological factors, including hormones, the environment and temperature. The studies on diurnal (circadian) variation in lymphocyte counts have demonstrated progressive increase in CD4 T-cell count throughout the day, while CD8 T cells and CD19+ B cells increase between 8.30 a.m. and noon with no change between noon and afternoon. Natural killer-cell counts, on the other hand, are constant throughout the day.(4) Circadian variations in circulating T-cell counts have been shown to be negatively correlated with plasma cortisol concentration.(5-7) In fact, cortisol and catecholamine concentrations control distribution and therefore, numbers of naive versus effector CD4 and CD8 T cells.(5) It is generally accepted that lower CD4 T-cell counts are seen in the morning compared to the evening(8) and during summer compared to winter.(9) These data therefore indicate that timing and consistency in timing of blood collection is critical when serially monitoring patients for lymphocyte subsets.

Interpretation

Interferon-gamma (IFN-gamma) and CD107a and CD107b expression below the defined reference range are consistent with a global impairment in CD8 T-cell function, most likely due to over immunosuppression.

 

IFN-gamma and CD107a and CD107b levels greater than the defined reference range are unlikely to have any clinical significance.

Clinical Reference

1. Betts MR, Casaza JP, Patterson BA, et al: Putative immunodominant human immunodeficiency virus-specific CD8 T-cell responses cannot be predicted by MHC class I haplotype. J Virol 2000;74:9144-9151

2. Peters PJ, Borst J, Oorschot V, et al: Cytotoxic T-lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med 1991;173:1099-1109

3. Venkataramanan R, Shaw LM, Sarkozi L, et al: Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients. J Clin Pharmacol 2001;41:542-551

4. Carmichael KF, Abayomi A: Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in HIV monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract # B11052

5. Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets. Blood 2009;113:5134-5143

6. Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating antigen presenting cells regulated by sleep. Sleep 2007;30:401-411

7. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Pyschosom Med 1997;59:42-50

8. Malone JL, Simms TE, Gray GC, et al: Sources of variability in repeated T-helper lymphocyte counts from HIV 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important. J AIDS 1990;3:144-151

9. Paglieroni TG, Holland PV: Circannual variation in lymphocyte subsets, revisited. Transfusion 1994;34:512-516

Analytic Time

3 days

Testing Algorithm

When multiple specimen types are required to perform a panel of tests, the laboratory will perform the tests for which the appropriate specimen type was received and the laboratory will cancel those for which the appropriate specimen was not received. Be advised that this may change the degree of interpretation received with the report.

Method Name

Flow Cytometry