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Asking for Help in Understanding Immune Panel (Lymphocyte) Results

Messages
86
Hi,

I posted a question about interpreting immune system panel results. Specifically, this has to do with understanding what optimal levels of cells such as CD19, CD3, CD4, CD8 and CD56 ought to be. I posted this question in one of the Treatment forums, and have not gotten any replies. Since this question is more of a diagnostic question, I thought I would include a link to it from here. (I don't know how to move a question from one forum to another, or even if that is possible.

Any help in understanding these test results would be appreciated. The answer to the above question is harder to find than I would have thought.

http://forums.phoenixrising.me/inde...et-a-lymphocyte-blood-test-cd4-cd8-etc.34522/

Thank you in advance.

Scotty81
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Dear Scotty81,
The numbers of these lymphocyte subsets in the blood are really not very important as long as they are reasonably near the standard range. Numbers of lymphocytes range hugely from person to person for reasons we do not know much about - particularly CD19 B cells and CD56 NK cells. If they are missing altogether that is another matter.

In most major immune disorders the subset numbers are normal. Lupus can have low total lymphocytes. The clinical assay systems are mostly there because of AIDS where CD4 cells are very low.

In other words, there is no such thing as 'optimal' here. These are just numbers of cells passing through the blood. They do not actually do anything in the bloodstream and some people seem to have faster throughput than others.
 

helen1

Senior Member
Messages
1,033
Location
Canada
Hi Scotty

I'm only familiar with CD4 & CD8. I didn't keep any links from my research but have these notes I can share. Apparently the CD4/CD8 ratio is what's most important for determining immune system health. Lab range is from 1 to 4 with optimal at 2 to 4. At 5 and above this would indicate either an autoimmune condition, sometimes a major infection (I know, this contradicts what I found below) or possibly leukemia.

Viral infections would cause a decreased ratio of 1 or under. Apart from viral infections, other factors affecting the ratio are seasonal variations, diurnal variations, lab analysis variations, HIV, corticosteroid use, MS, aplastic anemia, leukemia (yep another contradiction), IRIS (especially possible if low CD4 count and low ratio).

Best,
Helen
 

helen1

Senior Member
Messages
1,033
Location
Canada
I wish I'd kept links, just took notes from researching. I see you have a different understanding of the lymphocytes @Jonathan Edwards and you clearly know a lot more than I do. I'm curious though if there's anything that I wrote that you might agree with, for example causes of high or low levels?

My apologies to Scotty if I've caused confusion.
 
Messages
86
Hi Jonathan and Helen1,

Thank you both for your replies. I do realize that interpreting lymphocyte results are not as easy as I thought. I do have a couple of follow up questions to determine if the immune system is really getting affected, and also if the results warrant further testing.

Compared to a reference range of [5-30] for % CD56, my family member's result was 7. That looks like on the low side of normal. Also, for the CD4/CD8 ratio, my family member's result is 1.12. So, that is no where close to 4 or 5, so that doesn't sound like she has an autoimmune condition or one of the other conditions you mentioned. As for % CD19, compared to a reference range of [5-25], my family member's result was 13%. Additionally, my family member also has an IL-10 result of < 5 pg/mL, whereas the reference range (for normal function) is < 18 pg/mL.

Do any of these results, by themselves, suggest any immune dysfunction and/or upregulation? Also, even though these results seem normal, can the NK cell function, which I've seen many postings about, still be abnormal? In other words, I'm not sure if there is value in getting NK cell function tested with the above results. From what I've seen online the NK cell function requires 10 ml of serum, which is a lot more than the typical 1-2 ml for other tests.

Finally, as an immunologist, is there any other basic immunologic testing that you might recommend (besides results that are included in CMP)? I've seen other people get an immunoglobulin subclasses panel or immunoglobulin IgG/IgM/IgA/IgE panel. Is that warranted at this time?

Thank you in advance.

Scotty81
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Dear Scotty81,
For these lymphocyte tests anywhere in the reference range is fine. Patients may get worried if results are at the lower end of a range but I don't think there is any reason to. In relation to CD4/8 I have never heard of the idea that any particular ratio is better than another as long as it is somewhere near the reference range. The main reason for looking at the ratio is for AIDS where the ratio is way off. The changes in other conditions are very variable. In my own lab we did not find unusual ratios in people with autoimmunity - I am not sure where that comes from. So I do not think any particular ratio indicates autoimmunity but equally a normal ratio does not indicate no autoimmunity. My rheumatoid arthritis patients had normal ratios.

So I do not think any of these tests tell you one way or the other about any immune dysfunction in the sense of autoimmunity. Autoimmune disease physicians do not ask for lymphocyte subsets except under very special circumstances because they do not help.

NK cell function tests in ME remain controversial. So far no consistency has been achieved in the findings. One of the problems I suspect is that reference ranges may be set up using fresh samples and patient samples coming by mail may not be so fresh. (What is needed is fresh unclotted whole blood, not serum, and it will be no good if it spends a long time in transit at the wrong temperature.) We desperately need to get this sorted out. But until it is sorted out I do not think NK function tests are even of value as a 'biomarker'. If NK cells are absent that is a different matter but function seems to be so susceptible to other factors that I cannot see it being something to base treatment on.

I am not familiar with 'CMP'. A standard immunoglobulin assay for IgM/IgA/IgG is certainly a reasonable thing to test for, together with immunoglobulin electrophoresis, but subclasses are unlikely to be useful. Unusual levels of Igs or individual bands can be helpful in situations where autoantibody tests are unhelpful. An antinuclear antibody screen would certainly be sensible.
 

deleder2k

Senior Member
Messages
1,129
@Jonathan Edwards, thank you for your replies. Interesting to read!

You say that lymphocytes range from person to person vary. But how much do they fluctuate? Over the years I've had an steady increase in lymphocytes count. I've tried googling around everywhere to find out how much they vary, but I can't find anything useful information. If I just knew the standard deviation or had some graphs, but I can't find anything!
 

Jonathan Edwards

"Gibberish"
Messages
5,256
@Jonathan Edwards, thank you for your replies. Interesting to read!

You say that lymphocytes range from person to person vary. But how much do they fluctuate? Over the years I've had an steady increase in lymphocytes count. I've tried googling around everywhere to find out how much they vary, but I can't find anything useful information. If I just knew the standard deviation or had some graphs, but I can't find anything!

I don't know how much they fluctuate for an individual over time. Maybe nobody has done a systematic study of that. What I have seen is a paper in the early days of AIDS (around 1984) showing that CD4 counts could change quite a lot just by putting the blood in the fridge. I think it is a bit like measuring the number of people in the street - it changes with time of day and if it is raining or a football match is on. There is no good reason to think numbers of lymphocytes in blood means much, I think.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
For what it's worth, Griffith uni had a cut off time from drawing blood to lab for testing. I belive klimas also does this and makes the test more accurate.

is it an important test, well if we look at its function of fighting viral and cancer infected cells, than no function is quite important.

Griffith university ate looking at designing a test or biomarker for cfsme. Cfsme vs healthy controls show a consistent difference of low nk function amongst Cfsme people but also nk bright cells. I have heard they are looking at doing these nk function and bright cell function and comparing them to RA patients and MS patients who are also known to have low nk function. Bright cell function i think may be the differing result.

so low nk function and bright cell function look promising for a test or biomarker. The Cfsme gurus who have been in the trenches for decades find value in nk function testing and use it in helping them diagnose Cfsme.

Treating this dysfunction helpful, possibly ????
Seems to help those with chronic viral infections.
 

Sinclair

Senior Member
Messages
129
Dear Scotty81,
For these lymphocyte tests anywhere in the reference range is fine. Patients may get worried if results are at the lower end of a range but I don't think there is any reason to. In relation to CD4/8 I have never heard of the idea that any particular ratio is better than another as long as it is somewhere near the reference range. The main reason for looking at the ratio is for AIDS where the ratio is way off. The changes in other conditions are very variable. In my own lab we did not find unusual ratios in people with autoimmunity - I am not sure where that comes from. So I do not think any particular ratio indicates autoimmunity but equally a normal ratio does not indicate no autoimmunity. My rheumatoid arthritis patients had normal ratios.

So I do not think any of these tests tell you one way or the other about any immune dysfunction in the sense of autoimmunity. Autoimmune disease physicians do not ask for lymphocyte subsets except under very special circumstances because they do not help.

NK cell function tests in ME remain controversial. So far no consistency has been achieved in the findings. One of the problems I suspect is that reference ranges may be set up using fresh samples and patient samples coming by mail may not be so fresh. (What is needed is fresh unclotted whole blood, not serum, and it will be no good if it spends a long time in transit at the wrong temperature.) We desperately need to get this sorted out. But until it is sorted out I do not think NK function tests are even of value as a 'biomarker'. If NK cells are absent that is a different matter but function seems to be so susceptible to other factors that I cannot see it being something to base treatment on.

I am not familiar with 'CMP'. A standard immunoglobulin assay for IgM/IgA/IgG is certainly a reasonable thing to test for, together with immunoglobulin electrophoresis, but subclasses are unlikely to be useful. Unusual levels of Igs or individual bands can be helpful in situations where autoantibody tests are unhelpful. An antinuclear antibody screen would certainly be sensible.

@Jonathan Edwards my CD4/CD8 ratio has been for a year well below the 1 range (0.56) and my NK cell count is 25 with a normal range starting in 55. You said "If NK cells are absent that is a different matter".

Could you please try to explain me whether I should be concerned beyond ME/CFS or not? Thanks in advance.
 

helen1

Senior Member
Messages
1,033
Location
Canada
My CFS doc is the one who requested the CD4 CD8 test. I will ask him tomorrow about what he thinks the significance is.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
@Jonathan Edwards my CD4/CD8 ratio has been for a year well below the 1 range (0.56) and my NK cell count is 25 with a normal range starting in 55. You said "If NK cells are absent that is a different matter".

Could you please try to explain me whether I should be concerned beyond ME/CFS or not? Thanks in advance.

I don't want to get in to advising everyone about their lymphocyte counts! Answering Scotty81 with results in the normal range is straightforward. A low CD4/8 ratio is clearly of significance in certain specific clinical situations and without information about your clinical situation and not being a registered medical practitioner anymore all I can say is that I think it unlikely that your results would add to clinical evaluation much unless there are other specific reasons to be concerned abut a low CD4 count. I am not personally aware of any reason to think the NK cell count is important.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
The subset test is non specific, but can help with diagnosing cfsme as it's a common finding that we have a dysfunctional immune system, although not everyone will show something. Plus it can possibly help diagnose other immune abnormalities.

I have mentioned this in many posts but high cd8 is a common finding in active herpes infections. So if one wants to confirm an active ebv infection for example but no igm titres for a new infection and has high igg titres which many cfs gurus say can indicate an active infection, a high cd8 reading can help confirm an active ebv infection. So high titres, elevated cd8 lymphocytes and viral symptoms are a good guide to ebv infection.

my Dr said that generally speaking elevated markers show the immune system is fighting something. If the subset markers are low than the immune system could be tiring from a chronic infection.

to rule out the dysfunction isn't just a flu type virus, it's probably worth doing a few tests several months apart and seeing if there's a pattern of immune dysfunction.