NK VUE Information for Medical Professionals

 

Natural Killer Cells

NK cells are large granular lymphocytes with a characteristic morphology which play a role in innate immunity. NK cells are classified as group 1 innate lymphoid cells (ILCs), are involved in the early defense against infection and tumors and may be involved in autoimmunity and hypersensitivity reactions. Recruitment of NK cells to the site of inflammation, infection or transformation is a first step in the response to infection and tumors, and occurs prior to the initiation of an adaptive immune response against infection or tumors.

The mechanisms by which NK cells defend the body are via immunosurveillance - targeted cell death and release of chemokines and cytokines (innate immune system), as well as via immunoregulation - helping other immune cells in their targeted cell elimination via the action of the NK-released cytokines (adaptive immune system), thus linking innate and cellular immunity.


Mechanisms
Activation
Response
NK cell
• Granzyme B
• Perforin
• Cytokines
Apoptosis      Necrosis
Cytotoxic response to tumor formation and viral-infected cells causing lysis or apoptosis
Controls adaptive immune response by releasing cytokines

 

The two main functions of NK cells, cytokine production and cytolytic activity, have been assigned to distinct NK cell population subsets, the NK CD56bright and NK CD56dim subsets (the bright subset being a developmental precursor to the dim subset). In vivo, it is the CD56dim subset that is responsible for cytoxocity whereas the CD56bright subset is not cytotoxic. CD56bright cells can be induced to become cytotoxic in response to cytokine stimulation. Both subsets release IFN-γ in response to cytokine stimulation.

 

Studies With NK VUE

NK VUE has been and is being studied in clinical trials in Korea, Canada, USA and Denmark.

NK CELL ACTIVITY AND COLORECTAL CANCER

The correlation between low NK cell activity (as measured by NK VUE) and the presence of colorectal cancer has been demonstrated in a published clinical trial. In a study of 41 patients with newly diagnosed colorectal cancer, researchers at Yonsei University College of Medicine in Korea discovered that the NK cell activity of patients in their study group was significantly lower than it was in the 41 healthy patients in the control group.1

In Canada a large clinical study is underway, examining 1000 patients undergoing a colonoscopy. The study will examine NK cell activity in patients whose colonoscopy does not show anything abnormal and compare the results to those of patients who have a biopsy-confirmed cancer.

 

1 Lee, S.-B. et al. A high-throughput assay of NK cell activity in whole blood and its clinical application. Biochem. Biophys. Res. Commun. 2014 Mar 14;445(3):584–590.

 

NK CELL ACTIVITY AND PROSTATE CANCER

The correlation between low NK cell activity (as measured by NK VUE) and the presence of prostate cancer has also been demonstrated in a published clinical trial. In a study of 54 newly diagnosed, biopsy-confirmed prostate cancer patients, researchers at Yonsei University College of Medicine in Korea found that NK cell activity in these patients was significantly lower than it was in the 54 healthy individuals in the control group.2

 

2 Koo, K. C. et al. Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer. PLoS ONE. 2013 Nov 4;8(11):e78049.

 

Please view our NK VUE PDF presentation for more information about our clinical trials, which can be also be downloaded in our resources section. For the latest information please visit our NEWS section.

Testing Recommendations

Based on the current experience with NK VUE in Korea, we can provide the following preliminary recommendations. This recommendation is provided as a tool to help in the interpretation of results; it is not a guideline. This recommendation may be changed at any time without notice when new clinical data becomes available.

Testing
Normal value
(≥500 pg/mL)
Alert value
(200-499 pg/mL)
Abnormal value
(<200 pg/mL)
Retest in
3-6 Months
2 Months
Normal
value
Alert
value
Abnormal
value
Healthy NK Cells
Annual Monitoring
Temp Low NK Cells
Annual Monitoring
Close Monitoring
Physician Orders
Additional Testing

 *Disclaimer: Reference ranges may vary based on performing laboratory's clinical validation studies.

 

Causes for temporarily low NK cell activity: acute stress, severe fatigue, sleep disorders, viral or bacteria infection, steroid based drugs, immunosuppressant drugs, lifestyle (diet, smoking, exercise, etc.)

Causes for consistently low NK cell activity: cancer or family history of cancer, autoimmune disorders, coronary heart disease, diabetes, chronic stress, chronic fatigue, pregnancy

 

If a patient’s NK cell activity is low, a doctor may want to further investigate the reasons for this. Lifestyle changes such as diet, exercise, or smoking cessation can help improve the immune system and may be recommended. For patients above the age of 50, a medical professional will assess the possible reasons for low NK cell activity and review risk factors. Other screening tests may be required.

 

MenWomenPossible Additional TestingNotes
  PSA Test To check for prostate cancer
  Rectal Exam
  Mammogram To check for breast cancer
  Ultrasound
Stool Test To check for colon cancer
Colonoscopy

 

Testing for NK Cell Activity

The activity of NK cells can be measured using the classical cytotoxicity assays (51Chromium assay) or newer non-radioactive fluorescent dye cytotoxicity assays. These tests measure only the cytotoxic potential of NK cells and do not measure their ability to engage other cell types involved in the adaptive immune response.

NK cell activity in vitro cannot be measured without stimulating NK cells since NK cells do not secrete effector cytokines ex vivo in the absence of appropriate activating stimuli. Using a stimulatory cytokine, one can analyse NK cell activity in whole blood (see figure below), which would include measurement of both the cytotoxic potential of the whole NK cell population (both CD56bright and CD56dimsubsets) as well as the ability of these cells to amplify the immune response to tumors. Both of these NK cells subsets release IFN-γ following cytokine stimulation. The amount of IFN-γ released is indicative of both the cytotoxic ability of the CD56dim subset and the immunomodulation by this cytokine, released from both subsets (CD56dim and CD56bright), to stimulate dendritic cells, and aid in the T-cell mediated antitumor response.

Principle of NK VUE

NK Vue employs a proprietary stabilized immunomodulatory cytokine (Promoca) to stimulate NK cells in whole blood. After their activation, a quantitative sandwich enzyme immunoassay (ELISA) is used to determine the levels of IFN-γ secreted. To this end, an anti-IFN-γ monoclonal antibody has been pre-adsorbed on a microwell plate. Samples are pipetted into the wells and IFN-γ allowed to bind to the immobilized antibody. After washing away all unbound material, a second anti-IFN-γ monoclonal antibody complexed to an enzyme (HRP) is added to the wells. Following a final wash to remove any unbound antibody-HRP complex, the substrate solution is added to the wells and color is allowed to develop. Absorbance at 450 nm is measured, and the amount of IFN-γ released by the NK cells is finally quantitated by comparison to an IFN-γ standard curve.

 

 
 
 
 
 
1
NK VUE TUBE
BLOOD 1 mL
2
PROMOCA
3
IFN-γ
RELEASE
4
PLASMA
HARVEST
5
SANDWICH
ELISA
6
RESULTS
NK CELL
37℃, 24 HRS
INCUBATION
ACTIVATED
NK CELL

 

Each NK Vue ELISA Kit contains enough reagents and materials to process 96 wells.

 

 

 

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