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©2013 UpToDate ® Print Email Approach to the diagnosis of NK cell deficiency Evaluation Test Technique Abnormal result• Notes Identification Lymphocyte subset analysis Fluorescence activated cell sorting (FACS) Absent or decreased Separate CD56 and CD16 evaluations◊ Ex Vivo function NK cytotoxicity ADCC Cytotoxicity assay Absent or decreasedΔ Always ship samples with an unrelated control§ In Vitro responsiveness Cytokine induced cytotoxicity and cytokine production Cytotoxicity assay Absent or decreased Stimulants include IL-2, IL-12, and IFN-α Intracellular FACS* Phenotype NK cell subset analysis FACS Missing/ decreased activation receptor or increased inhibitory receptor Specific receptor function Redirected lysis and other antibody or ligand directed assays Cytotoxicity assay, granule release, Ca++ flux and others Decreased activity after specific receptor ligation. * A major cytokine produced by NK cells that is presumably of biologic relevance is IFN-Γ. This factor can be measured intracellularly in NK cells most easily after short-term exposure to mitogen. • Although it is difficult to interpret a decreased result, values that are persistently lower than the reference range for the laboratory experienced in the investigation may be of significance and worthy of further study. Δ Decreased ex vivo NK cell function in total PBMC preparations may be due to decreased NK cell numbers and thus may be a defect of NK cell production or survival and not that particular function. If the patient possesses a small population of NK cells this issue can be addressed using purified or enriched NK cells. ◊ Many clinical laboratories use a reagent to identify NK cells that contains anti-CD3-FITC as well as both anti-CD56-PE and anti-CD16-PE. Although this reagent will identify NK cells it will overlook all patients with an alteration of CD16. In suspected cases both CD16 and CD56 should be evaluated separately. Anti-CD16 clone 3G8 will recognize variant receptors while clone B73.1 will not. Both reagents are commercially available. § Extreme conditions during shipping can affect biological activity and thus a shipping control is necessary. It is important that the control be unrelated, as some NK deficiencies are present in families.