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Test Code CMVC8 Cytomegalovirus (CMV) CD8 T-Cell Immune Competence, Quantitative Assessment by Flow Cytometry, Blood

Reporting Name

CMV CD8 T-Cell QN by Flow Cytometry

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Useful 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

Method Name

Flow Cytometry


Ordering 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 Type

WB Sodium Heparin

Specimen Minimum Volume

10 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
WB Sodium Heparin Ambient 48 hours GREEN TOP/HEP

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject

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+.

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.

Day(s) Performed

Monday through Friday

Report Available

3 to 6 days

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