Home
HelpTest Code CMVC8 Cytomegalovirus (CMV) CD8 T-Cell Immune Competence, Quantitative Assessment by Flow Cytometry, Blood
Test Down Notes
This test is temporarily unavailable due to reagent issues. For additional details, see test update here.
Reporting Name
CMV CD8 T-Cell QN by Flow CytometryUseful For
Assessing cytomegalovirus (CMV)-specific immune competence in allo-hematopoietic stem cell transplantation patients who are at risk for developing late CMV disease (beyond day 100 after transplant)
Assessing CMV-specific immune competence in solid organ transplant patients who are at high risk for CMV reactivation posttransplant
Monitoring immune competence in patients post-primary CMV infection after transplant who are at risk for CMV reactivation after the cessation of antiviral prophylaxis
Identifying individuals who are likely to be protected from posttransplant CMV infection and those who are at higher risk of CMV reactivation
The global CD8 T cell immune competence assay is 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
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
WB Sodium HeparinOrdering Guidance
Patient must be cytomegalovirus seropositive and have 1 or more of the 5 major histocompatibility complex alleles: HLA A1, A2, B7, B8, or B35 to utilize this assay.
Additional Testing Requirements
It is important to ascertain the patient's and the donor's cytomegalovirus serostatus, as well as the patient's major histocompatibility complex class I HLA haplotype, before ordering this assay; see 1DIS / Human Leukocyte Antigens (HLA) A-B-C Disease Association Typing Low Resolution, Blood.
Shipping Instructions
Testing performed Monday through Friday. Specimens not received by 4pm (CST) on Friday may be cancelled.
Collect and package specimen as close to shipping time as possible. Ship specimen overnight in an Ambient Shipping Box-Critical Specimens Only (T668) following the instructions in the box. It is recommended that specimens arrive within 24 hours of collection.
Samples arriving on the weekend and observed holidays may be canceled.
Necessary Information
Ordering healthcare professional name and phone number are required.
Specimen Required
Supplies: Ambient Shipping Box-Critical Specimens Only (T668)
Container/Tube: Green top (sodium heparin)
Specimen Volume: 20 mL
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.
Additional Information: For serial monitoring, it is recommended that specimens are collected at the same time of day.
Specimen Minimum Volume
10 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| WB Sodium Heparin | Ambient | 48 hours | GREEN TOP/HEP |
Special Instructions
Reference Values
Total CD3 T cells: 884-5830 x 10(3)/mL
Total CD8 T cells: 168-1847 x 10(3)/mL
Total CMV CD8 T cells: 0-115 x 10(3)/mL
The adult reference values were determined for healthy adult controls ages 20 to 80 years (n=94), for HLA A1, A2, B7, B8, and B35 alleles.
Reference values for cytomegalovirus (CMV) specific T cells that are functional (interferon-gamma+, IFN-g+) and have cytotoxic activity (CD107a and CD107b expression, CD107 a/b+):
Total CMV CD8 T-cells IFN-g: 0.028-52.200 x 10(3)/mL
Total CMV CD8 T-cells CD107a/b: 0.252-50.760 x 10(3)/mL
The 95% confidence interval reference values were determined from 102 healthy adult donors:
Interferon-gamma (IFN-gamma) expression (as % CD8 T cells): 10.3-56.0%
CD107a/b expression (as % CD8 T cells): 8.5-49.1%
The reference values were developed for each of the following 4 major histocompatibility complex class I alleles: A1, A2, B7, and B8 (n=45). We were unable to develop ranges for the B35 allele due to a lack of matching donors. The data is expressed as the absolute number of CMV-specific CD8 T cells that are IFN-gamma+ or CD107a/b+.
Day(s) Performed
Monday through Friday
Test Classification
This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
86356 x 6
86359
86352
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CMVC8 | CMV CD8 T-Cell QN by Flow Cytometry | 95184-8 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 28143 | Total CD3 T cells | 8122-4 |
| 28144 | Total CD8 T cells | 14135-8 |
| 28145 | CMV CD8 T cells A1 | 95185-5 |
| 28146 | CMV CD8 T cells A2 | 95202-8 |
| 28147 | CMV CD8 T cells B7 | 95201-0 |
| 28148 | CMV CD8 T cells B8 | 95200-2 |
| 28149 | CMV CD8 T cells B35 | 95199-6 |
| 28150 | Total CMV CD8 T cells | 95198-8 |
| 28151 | CMV CD8 T cells IFN-g A1 | 95197-0 |
| 28152 | CMV CD8 T cells IFN-g A2 | 95196-2 |
| 28153 | CMV CD8 T cells IFN-g B7 | 95195-4 |
| 28154 | CMV CD8 T cells IFN-g B8 | 95194-7 |
| 28155 | CMV CD8 T cells IFN-g B35 | 95193-9 |
| 28156 | Total CMV CD8 T cells IFN-g | 95192-1 |
| 28157 | CMV CD8 T cells CD107 A1 | 95191-3 |
| 28158 | CMV CD8 T cells CD107 A2 | 95190-5 |
| 28159 | CMV CD8 T cells CD107 B7 | 95189-7 |
| 28160 | CMV CD8 T cells CD107 B8 | 95188-9 |
| 28161 | CMV CD8 T cells CD107 B35 | 95187-1 |
| 28162 | Total CMV CD8 T cells CD107a/b | 95186-3 |
| 30693 | IFN-gamma expression | 95204-4 |
| 30694 | CD107a/b expression | 95203-6 |
| 28163 | Interpretation | 69052-9 |
Interpretation
For allogeneic hematopoietic stem cell transplantation (HSCT) and solid organ transplant patients who are cytomegalovirus (CMV)-seropositive and at risk for CMV reactivation, posttransplant results should be compared to pretransplant (preconditioning/baseline) results.
The report includes absolute CD3 and CD8 T-cell counts as well as a derived CMV-specific CD8 T-cell count (derived from CD3 and CD8 T-cell counts). The absolute count of CMV-CD8 T cells that are activated and have cytotoxic function in response to specific CMV peptide is also provided. The data from the 3 components of this assay should be interpreted together and not individually.
In the setting of CMV viremia, frequent monitoring of CMV-immune competence helps define the evolution of the CMV-immune response. In this clinical context, CMV-immune competence should be measured as frequently as viral load to determine correlation between the 2 parameters. CMV-specific CD8 T-cell counts may show a decline in numbers over time in the absence of active infection or antigenemia.
The absence of CMV-specific CD8 T cells may be a risk factor in the immune-compromised or immune-incompetent transplant patient, who is at risk for CMV reactivation. The presence of CMV-specific CD8 T cells may not be protective in itself. If the CMV-specific CD8 T cells do not show appropriate cytotoxic function (due to the fact that they recognize CMV epitopes that do not effectively induce a cytotoxic response), these patients may be at higher risk of an inadequate immune response to CMV infection.
While the reference values provide a guideline of CMV-specific CD8 T-cell numbers and function in a cohort of healthy individuals, baseline (pretransplant/preconditioning) assessments should be taken into consideration when determining CMV-specific immune competence posttransplant. Correlation between data from multiple post-transplant specimens (if available) and the presence or absence of viremia (or active CMV disease) also are useful in the interpretation of results.
CD8 T cell counts are elevated when the immune system is initially reconstituted post-HSCT, and the CD4 to CD8 ratio can be inverted for about 12 months post-HSCT.
Interferon-gamma (IFN-gamma) and CD107a/b 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/b levels greater than the defined reference range are unlikely to have any clinical significance.
Clinical Reference
1. Melnick JL, Adam E, Debakey ME. Cytomegalovirus and atherosclerosis. Eur Heart J. 1993;14 Suppl K:30-38
2. von Willebrand E, Petterson E, Ahnonen J, Hayry P. CMV infection, class II antigen expression, and human kidney allograft rejection. Transplantation. 1986;42(4):364-367
3. Hakki M, Riddell SR, Storek J, et al. Immune reconstitution to CMV after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood. 2003;102(8):3060-3067
4. Baden LR. Pharmacokinetics of valganciclovir in HSCT patients with gastrointestinal GVHD. Biol Blood Marrow Transplant. 2005;15(2):5-7
5. Bachier C, Shaughnessy P, Wall D, et al. Valganciclovir for the prophylaxis of early cytomegalovirus (CMV) infection after allogeneic stem cell transplantation,. Biol Blood Marrow Transplant. 2005;11(2):90-91
6. Annaloro C, Serpenti F, Saporiti G, et al. Viral infections in HSCT: Detection, monitoring, clinical management, and immunologic implications. Front Immunol. 2021;11:569381. doi:10.3389/fimmu.2020.569381
7. Boeckh M. Prevention of late CMV infection in HSCT. Biol Blood Marrow Transplant. 2005;15(2):9-11
8. Li CR, Greenberg PD, Gilbert MJ, et al. Recovery of HLA-restricted CMV-specific T cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood. 1994;83(7):1971-1979
9. Meesing A, Abraham RS, Razonable RR. Clinical correlation of cytomegalovirus infection with CMV-specific CD8+ T-cell Immune competence score and lymphocyte subsets in solid organ transplant recipients. transplantation. 2019;103(4):832-838. doi:10.1097/TP.0000000000002396
10. Carmichael KF, Abayomi A. Analysis of diurnal variation of lymphocyte subsets in healthy subjects in the Caribbean, and its implication in HIV monitoring and treatment. Afr J Med Med Sci. 2006;35(1):53-57
11. Dimitrov S, Benedict C, Heutling D, et al. Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets. Blood. 2009;113(21):5134-5143
12. Dimitrov S, Lange T, Nohroudi K, Born J. Number and function of circulating antigen presenting cells regulated by sleep. Sleep. 2007;30(4):401-411
13. 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(1):42-50
14. Paglieroni TG, Holland PV. Circannual variation in lymphocyte subsets, revisited. Transfusion. 1994;34(6):512-516
15. 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 Acquir Immune Defic Syndr (1988). 1990;3(2):144-151
Report Available
3 to 6 daysMethod Name
Flow Cytometry