Help NK cells test results interpretation

[serg1942]

Hi all,

I just posted this message in other thread and thought this would be the proper section to be posted:

I just received my NKs cells meassurement:

% CD8-/CD57+ Lymphs: 1 (2-17) %
Abs. CD8-CD57+ Lymphs: 9 (60-360) /uL

(How can I be living with so few NKs!!!! ;-)

I'm trying hard to figure out the exact interpretation of these results. I was tested for them as a possible marker for the degree of Lyme disease, but my Igenex test showed a "clear" (all the clear this can be) negative for Borrelia. So, I wonder if XMRV can be lowering my NKs so much, as HIV has shown to do.

Any way, I'd very much like to understand these results. Could you help me with this? This are my questions:

- Which is the difference between CD56 and CD57 when it comes to the assessment of NK cells status?

- What the value given in % means?--I read some studies referring to activity of NKs, using percentages as units, but I cannot understand this...Which are the usual units to measure the activity of NK cells?

- The second measurement seems to be the absolute count of NKs (at least the ones expressing the CD57 membrane protein ...), but again, the units confuse me, as they wrote "/uL)". I assume "uL" stands for microlitres, but then, it should be "something/microlitres"...

Any thoughts will be very appreciatted,

Thanks, and please pardon my english,
Sergio

 

[Wasbeer]

Hi Sergio,

where and how did you get these measurements done? Didi you have to pay for it? I hope someone can help you with the interpretation. Good luck!

Eelco

 

[Dr. Yes]

Hi Sergio,

CD56 is a more common marker on NK cells than CD57. Therefore CD56 NK counts will give you a larger census of your total NK population. CD57 NK counts, as you probably know, have been suspected of being reduced in Lyme patients. A negative Igenex test does not mean you cannot still have Lyme, though you could say it is less likely. Bear in mind that some Lyme doctors no longer consider the CD57 count to be an index for Lyme infection.

The % figure is the percentage of your total lymphocytes that express CD57 (and don't express CD8, thereby restricting this group to a subset of NK cells). This is not a measure of NK cell activity (also called function). NK function is measured in lytic units (LU) or occasionally a percentage is given - but your results are not of NK activity/function, but of count. There's more on the function topic in this thread:

http://www.forums.aboutmecfs.org/showthread.php?4899-What-is-considered-low-NK-cell-function

The second result they gave you is an absolute CD57 NK cell count, measured in cells per microliter of blood.

Your count is very low indeed, if the result is accurate. I don't know enough to tell you what else besides Lyme might lower CD57 NK counts, apart from Mycoplasma (according to Garth Nicolson). I don't think anyone knows yet whether XMRV can lower them, but it sounds possible to me. If you wanted a wider angle view of your NK status, you would need a CD56+ NK cell count and an NK function test.

 

[serg1942]

Hi Wasbeer and Dr. Yes,

Wasbeer,

this test was run at LabCorp. I am residing in the states, but am Spanish, so have no insurance that pays for this...Not sure whether insurances for American people pay for this test, though…

Dr. Yes,

Thanks so much for your detailed post. I’ve read the thread you recommended and also have dusted off my immunology book! ;-)

It’s a pity that my results do not reflect the activity of my NK, but I assume that by having so low count of NKs, their global activity must be very reduced (unless they are superNKs, and I doubt it! ;-).

Let me ask you a few questions:

According to my immunology book, NK cells cannot be considered either linf B or T. They do not express CD3 protein membrane (so they are not linf C.) and the don’t express B Cell Receptor nor T Cell Receptor either (so they are not T or B cells).

However, (according to my book), some of them express CD8, and all of them express CD16, CD56 and CD57.

The book concludes that, unlike for other cells, NKs don’t have a specific marker, so their definition is more functional (another reason for the preference of measuring their activity).

I have had a look to a few papers, and some of them use CD8-CD16+, others CD8-CD56+ and others CD8-CD57+. Another one was measuring both CD8-CD16+CD56+…

If this is correct, we are always missing some NKs, as some of them express CD8. But my doubt is why do you say the CD56 is a better marker for them? Could you give me some reference of this?

Thanks and pardon my English!!
Sergio

P.S. I forgot a question: If the results given in percentages don't mean activity, then what do they mean? You wrote that they mean the % of the lymphocytes not expressing CD8. Well, all lymphocytes T express CD8, and the linf B (not expressing CD8) don't express CD57...So, then, to which cells does this % pertain? Are you sure this doesn't reflect activity?

 

[mhj]

Hi serg1942

You said:

I just received my NKs cells meassurement:

% CD8-/CD57+ Lymphs: 1 (2-17) %
Abs. CD8-CD57+ Lymphs: 9 (60-360) /uL

I am not sure that these result directly reflect yours NK cells. I have all my test taken by Redlabs, so i can only tell about that.

From Redlabs: http://www.redlabs.be/

CD57+/CD3- ABSOLUTE CELL COUNT: CD57+/CD3- cells are a subset of NK cells. Their exact function, and what differentiates

them from CD56+ NK cells, is not well understood. The absolute number of CD57+/CD3- cells is low in patients suffering from chronic

Lyme disease (a disease that follows an infection by a bacteria called Borrelia). Patients with very low CD57 have significantly more

co-infections and persistent immunologic defects than patients with higher counts. In patients that respond to antibiotic therapy, the

number of cells come back to normal, hence this is a useful marker to follow the effect of a therapy.

The result gives the absolute number of CD57 positive, CD3 negative cells per l of whole blood. The normal range is 60-360 cells/l.

Pasients with low CD57 count and high serum C4a might have/suspect problems with mold. If Borrelia is negativ, they perform a Zoonosis.

Back to the NK-cells test:

1. NK cell activity - perforin expression:

PERFORIN EXPRESSION ASSAY

Background

Natural Killer cells (NK) cells are cytotoxic cells that mediate the immune response against certain cancer and virus-infected cells. NK

cells are normally found in the peripheral blood, and are classified by their cell surface markers as CD3-/CD56+cells. NK cells activity

is altered in several disorders such as multiple sclerosis, lupus, and CFS, and is very sensitive to various environmental pollutants.

Since NK cells play a central role in the defense against viruses, decreased NK activity can lead to the development of opportunistic

viral infections. NK cells exert their cytotoxic effect by releasing perforin, a protein that will destroy the cytoplasmic membrane of target

cells and finally kill them.

Reference range: 250,00 - 750,00

2. Lymphocyte subsets, Immunophenotyping: A better meassurement for NK-cells!

NK-cells: CD16CD56+ (1,90 - 19,60%)

Often comes with T-cells subsets
T-cells CD3+ (62,00 - 84,40 %)
T-helper: CD3+CD4+ (29,00 - 67,10 %)
T-cytotoksisk/T-suppressor: CD3+CD8+ (10,50 - 44,30%)
Ratio CD4 og CD8: CD4/CD8 (0,72 - 2,89)

About NK-cells Wiki: http://en.wikipedia.org/wiki/Natural_killer_cell

In this article is there som interesting issues and results about NK-cells as well: Immune and hemorheological changes in Chronic

Fatigue Syndrome. http://www.translational-medicine.com/content/8/1/1.

--------------------------------------------------------------
Well your CD57 is very low, and you probably need some more test for hoepfully find the reason for your low counts.

See also this thread http://www.forums.aboutmecfs.org/showthread.php?4899-What-is-considered-low-NK-cell-function.

OK

My NK-cells results: :tear:
CD57: 49,1 (60 - 360)
NK-cell activity, perforin: 60,1 (250 - 750)
CD16CD56+: 5 (1,9 19,60 %)

 

[Dr. Yes]

However, (according to my book), some of them express CD8, and all of them express CD16, CD56 and CD57.

Almost all of them express CD56, but they don't all express CD57.

NK cells are practically defined in most texts by CD56 positivity (as well as CD3 negativity), and they can be further classified as either "dim" or "bright" in their level of CD56 expression. About 50% of CD56 'dim' are also CD57+, while less than 10% of CD56 'bright' are. (Also, both major subsets are 30-40% CD8+).

[source: Lotzova, Herberman, ed. NK Cell Mediated Cytotoxicity: Receptors, Signaling, and Mechanisms; CRC press 1992, p.188: Table 1: Characteristics of Human NK Cell Subsets]

http://books.google.com/books?id=u0...um=8&ved=0CEkQ6AEwBw#v=snippet&q=CD57&f=false

However, CD56 dim cells are far more abundant in the blood than CD56 bright (the latter are much more abundant in the lymph nodes and tonsils):
http://bloodjournal.hematologylibrary.org/cgi/content/full/112/3/461

So, in a healthy person's blood, almost all NK cells should be CD56+ and up to 50% would be CD57+ .

If this is correct, we are always missing some NKs, as some of them express CD8. But my doubt is why do you say the CD56 is a better marker for them? Could you give me some reference of this?

See above; greater than 90% of NK cells are CD56+, so they aren't missing many... the only reference I have at hand right now is Meier et al (2005) which states "Most NK cells (90%) are CD56dim." [They are referring to the blood.]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1211534/

P.S. I forgot a question: If the results given in percentages don't mean activity, then what do they mean?

They mean counts, as in the number of lymphocytes expressing certain markers specific to NK cells. A low count means the presence of that NK cell subtype has been reduced, in this case for some unknown reason.

You wrote that they mean the % of the lymphocytes not expressing CD8. Well, all lymphocytes T express CD8, and the linf B (not expressing CD8) don't express CD57...So, then, to which cells does this % pertain? Are you sure this doesn't reflect activity?

While NK cells are not as well understood as other lymphocytes, and while there isn't one marker they all share, they are considered a distinct lineage of immune cells. Your lab result is a count of lymphocytes that are CD8-, CD57+, which essentially means a subset of NK cells.

Counts are not a measure of activity; NK 'activity' is generally considered to be the same as "function", or "cytotoxicity" to be more exact, so perhaps those are a better terms to use. In laboratory assays, an NK cell's function is determined by how effective, on average, any single NK cell is likely to be at killing a target cell. So even if your number of cells is very low, you don't necessarily know how "healthy" those few cells are. They may be perfectly functional, just few in number.

Hope that helps. Your lab result is certainly unusual and it would be useful to know how the total NK population has been effected (i.e. look at CD56+/CD3- cell count), and to see if the ratios of any immunophenotypes are different (you would need a more thorough flow cytometric assay of NK cells to determine this). A functional assay is a separate test, but would also be useful to run. Of course, that all depends on how much you can afford to spend on testing...You don't want to wind up running out of money for any hypothetical treatment (whatever that may be) for whatever is going on!

 

[serg1942]

To mhj and Dr. Yes, NK cells

Hi mhj and Dr. Yes,

Thank you so much guys for your so detailed response! It is really very apprecitted!

I have read all the links you’ve given to me, and yes, it seems clear than the best marker for NK cells count, is CD3-CD56+, although, of course, the function should be the desirable thing to know...

I misunderstood my book. It has a table showing “-“, “+” or ”some” for the differents CD proteins expressed by NK cells, and it says: “some CD8”, “-CD3”, “+CD56” and “+CD57”. It seems then, than the symbol “+” means “many of them”, and not “all”!!

Anyway, it’s good to fully understand finally my results, although I still have a remaining question:

DR YES,

My results are: %CD8-/CD57+: 1 (2-17) %

Are you saying that this percentage pertains to the whole estimated group of NK cells??? In other words, what cells do you thing complete the rest 83%?

Thanks again for your help!
Sergio

 

[WillowJ]

is this an actual NKCC test?

http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=34184X&labCode=QDV

Test Code
34184X
CPT Code(s)
88184, 88185 (x2)