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Test Code QNKS Natural Killer (NK)/Natural Killer T-Cell Subsets, Quantitative, Blood

Useful For

Quantitation of the major natural killer (NK)-cell subsets relative to total NK cells (NK cell subsets) or total lymphocytes (NK T cells)

 

Assessment in the following clinical contexts: HIV, primary immune deficiencies with NK cell defects, NK-cell lymphocytosis, solid-organ transplantation, immune reconstitution following bone marrow or hematopoietic cell transplantation

 

This test is not useful for diagnosis or classification of NK cell malignancies.

 

This test should not be used for assessing NK cell cytotoxic function.

Reporting Name

Quantitative NK/NKT Subsets

Specimen Type

WB Sodium Heparin

Specimen Minimum Volume

0.2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
WB Sodium Heparin Ambient 30 hours GREEN TOP/HEP

Reference Values

The appropriate age-related reference values will be provided on the report. Pediatric reference values are not available for patients younger than 7 years and therefore, interpretation will be based on the 7- to 17-year old ranges with appropriate cautionary statements in the interpretation.

Interpretation

Interpretive comments will be provided, where applicable, along with reference range values for adult patients and pediatric patients from age 7 to 17 years. Since a separate pediatric reference range could not be established for patients younger than 7 years at this time, interpretation of these samples will be made using the 7- to 17-year old reference range as an approximate guideline.

Clinical Reference

1. Fan YY, Yang BY, Wu CY. Phenotypically and functionally distinct subsets of natural killer cells in human PBMCs. Cell Biol Int. 2008;32(2):188-197

2. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633-640

3. Poli A, Michel T, Theresine M, Andres E, Hentges F, Zimmer J. CD56bright natural killer (NK) cells: an important NK cell subset. Immunology. 2009126(4):458-465. doi:10.1111/j.1365-2567.2008.03027.x

4. von Bubnoff D, Andres E, Hentges F, Bieber T, Michel T, Zimmer Jl. Natural killer cells in atopic and autoimmune diseases of the skin. J Allergy Clin Immunol. 2010;125(1):60-68. doi:10.1016/j.jaci.2009.11.020

5. Vossen MT, Matmati M, Hertoghs KM, et al. CD27 defines phenotypically and functionally different human NK cell subsets. J Immunol. 2008;180(6):3739-3745. doi:10.4049/jimmunol.180.6.3739

6. Suarez-Alvarez B, Lopez-Vazquez A, Baltar JM, Ortega F, Lopez-Larrea C. Potential role of NKG2D and its ligands in organ transplantation: a new target for immunointervention. Am J Transplant. 2009;9(2):251-257. doi:10.1111/j.1600-6143.2008.02526.x

7. Borrego F, Robertson MJ, Ritz J, Pena J, Solana R. CD69 is a stimulatory receptor for NK cell and its cytotoxic effect is blocked by CD94 inhibitory receptor. Immunology. 1999;97(1):159-165. doi:10.1046/j.1365-2567.1999.00738.x

8. Takahashi K, Aranami T, Endoh M, Miyake S, Yamamura T. The regulatory role of natural killer cells in multiple sclerosis. Brain. 2004;127(Pt 9):1917-1927. doi:10.1093/brain/awh219

9. Alter G, Malenfant JM, Altfeld M: CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods. 2004;294(1-2):15-22

10. Mathew PA, Chuang SS, Vaidya SV, Kumaresan PR, Boles KS, Pham HTK. The LLT1 receptor induces IFN-gamma production by human natural killer cells. Mol Immunol. 2004;40(16):1157-1163. doi:10.1016/j.molimm.2003.11.024

11. Godfrey DI, Stankovic S, Baxter AG. Raising the NKT cell family. Nat Immunol. 2010;11(3):197-206. doi:10.1038/ni.1841

12. Orange JS. Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol. 2006;6(6):399-409

13. Marsh RA, Villaneuva J, Kim MO, et al. Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations. Clin Immunol. 2009;132(1):116-123. doi:10.1016/j.clim.2009.03.517

14. Rigaud S, Fondaneche MC, Lambert N, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature. 2006;444:110-114. doi:10.1038/nature05257

15. Villanueva J, Lee S, Giannini EH, et al. Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome. Arthritis Res Ther. 2005;7:R30-R37. doi:10.1186/ar1453

16. Tarazona R, Casado JG, Delarosa O, et al. Selective depletion of CD56(dim) NK cell subsets and maintenance of CD56(bright) NK cells in treatment-naive HIV-1-seropositive individuals. J Clin Immunol. 2002;22(3):176-183. doi:10.1023/a:1015476114409

17. Mavilio D, Lombardo G, Benjamin J, et al. Characterization of CD56-/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals. Proc Natl Acad Sci USA. 2005;102(8):2886-2891. doi:10.1073/pnas.0409872102

18. Timmons BW, Cieslak T. Human natural killer subsets and acute exercise: a brief review. Exerc Immunol Rev. 2008;14:8-23

19. Muntasell A, Magri G, Pende D, Angulo A, Lopez-Botet M. Inhibition of NKG2D in NK cells by cytokines secreted in response to human cytomegalovirus infection. Blood. 2010;115(25):5170-5179. doi:10.1182/blood-2009-11-256479

20. Trempat P, Tabiasco J, Andre P, et al. Evidence for early infection on nonneoplastic natural killer cells by Epstein-Barr virus. J Virol. 2002;76(21):11139-11142. doi:10.1128/jvi.76.21.11139-11142.2002

21. Pacheco SE, Gottschalk SM, Gresik MV, Dishop MK, Okmaura T, McCormick TG. Chronic active Epstein-Barr virus infection of natural killer cells presenting as severe skin reaction to mosquito bites. J Allergy Clin Immunol. 2005 Aug;116(2):470-472. doi:10.1016/j.jaci.2005.04.044

22. Mace EM, Orange JS. Emerging insights into human health and NK cell biology from the study of NK cell deficiencies. Immunol Rev. 2019;287(1):202-225

23. Delmonte OM, Fleisher TA. Flow cytometry: Surface markers and beyond. J Allergy Clin Immunol. 2019;143(2):528-537

24. Knight V, Heimall JR, Chong H, et al. A toolkit and framework for optimal laboratory evaluation of individuals with suspected primary immunodeficiency. J Allergy Clin Immunol Pract. 2021;9(9):3293-3307.e6

Day(s) Performed

Monday through Friday

Report Available

3 to 4 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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 x3

86359

86357

LOINC Code Information

Test ID Test Order Name Order LOINC Value
QNKS Quantitative NK/NKT Subsets 98073-0

 

Result ID Test Result Name Result LOINC Value
QNKSI Quantitative NK/NKT Interpretation 69052-9
NKA45 Total Lymphs (CD45+) 27071-0
NKP3N % Total CD45+CD3- cells 89311-5
NKA3N Total CD45+CD3- cells 89313-1
NKP % Total NK Cells 8112-5
NKA Total NK Cells 9728-7
NKPCY % Cytotoxic NK (CD16++CD56+) 42189-1
NKACY Cytotoxic NK (CD16++CD56+) 42188-3
NK56P % Cytokine-Producing NK (CD56++) 8133-1
NK56A Cytokine-Producing NK (CD56++) 14113-5
NKPL3 % Total CD45+CD3+ Cells 56907-9
NKAL3 Total CD45+CD3+ Cells 89312-3
NKTP % NKT cells (CD3+CD56+) 17135-5
NKTA NKT cells (CD3+CD56+) 26858-1

Method Name

Flow Cytometry


Ordering Guidance


This assay does not measure cell-surface or intracellular proteins on natural killer or natural killer T-cell subsets.

 

A minimum CD45 lymph count (as measured by flow cytometry in the laboratory) is required to report this test. If that requirement is not met (eg, patients with severe lymphopenia), the test will be canceled and an alternate test will be suggested (TBBS / Quantitative Lymphocyte Subsets: T, B, and Natural Killer [NK] Cells, Blood).



Shipping Instructions


Send specimen Monday through Thursday only. Specimen must arrive within 24 hours of collection and by 10 a.m. Central time on Friday.

 

Collect and package specimen as close to shipping time as possible. Ship specimen overnight.



Necessary Information


The ordering healthcare professional's name and phone number are required.



Specimen Required


Container/Tube: Green top (sodium heparin)

Specimen Volume: 3 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.