In trying to get IVIG - got some immunological test results back

[Marky90]

So I went to one of the main hospitals in Norway with a igG2 deficiency, and in that context I did thorough immunological blood tests. There were some deficiencies, but I dont know what they mean. They said that they see it in a lot of autoimmune diseases.. (I got tested for the known ones). The main imunnological doctor were going to propose that i could have benefit from IVIG to another hospital..

They results were:

B-CD3 (t-cells) 436*10E6/L 800-2400 (under the reference area)
B-CD4 (t-cells) 286 * 10E6/L 500-1400 (under the reference area)
B-CD8 (t-cells) 152 * 10E6/L 200-1000 (under the reference area)
B-CD19 (B-cells) 60 * 10E6/L 100-150 (under the reference area)
B-CD4+ naive t-cells 99.0 % of cd4 reference area: 25.0-71.0 (over the reference area)

The lab workers wrote in this context: "Approximately 33 % of the CD4+ T-lymphocytes are CD45RA and CDRO double positive. This finding has uncertain meaning, and should be controlled with new tests at a later time. The rest of the T-cell subpopulations has normal distribution.

Also:

TSH 3.8 (0.50-3.6) (over the reference area)

And borderline:

B-plasmablasts: 0.4. Reference area: 0.3-5.1.

LD, albumin. albumin( electrophoresis) were also above the reference area.

Anyone have any insights..

Would you be so kind to share your thoughts @Jonathan Edwards?

 

[Marky90]

Found this from another thread.. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270541/

 

[Jonathan Edwards]

So I went to one of the main hospitals in Norway with a igG2 deficiency, and in that context I did thorough immunological blood tests. There were some deficiencies, but I dont know what they mean. They said that they see it in a lot of autoimmune diseases.. (I got tested for the known ones). The main imunnological doctor were going to propose that i could have benefit from IVIG to another hospital..

They results were:

B-CD3 (t-cells) 436*10E6/L 800-2400 (under the reference area)
B-CD4 (t-cells) 286 * 10E6/L 500-1400 (under the reference area)
B-CD8 (t-cells) 152 * 10E6/L 200-1000 (under the reference area)
B-CD19 (B-cells) 60 * 10E6/L 100-150 (under the reference area)
B-CD4+ naive t-cells 99.0 % of cd4 reference area: 25.0-71.0 (over the reference area)

The lab workers wrote in this context: "Approximately 33 % of the CD4+ T-lymphocytes are CD45RA and CDRO double positive. This finding has uncertain meaning, and should be controlled with new tests at a later time. The rest of the T-cell subpopulations has normal distribution.

Also:

TSH 3.8 (0.50-3.6) (over the reference area)

And borderline:

B-plasmablasts: 0.4. Reference area: 0.3-5.1.

LD, albumin. albumin( electrophoresis) were also above the reference area.

Anyone have any insights..

Would you be so kind to share your thoughts @Jonathan Edwards?

All lymphocyte subsets are a bit low on that test. I am not sure what that would mean. It is probably worth repeating the test another time to see if it is consistent. I doubt that any of these figures are low enough to cause problems in themselves. If your IgG2 is low then maybe there is some more general regulatory shift. I am afraid I cannot say anything very definite.

 

[Ema]

What was your total IgG level? Were any other subclasses low besides IgG2?

 

[Marky90]

What was your total IgG level? Were any other subclasses low besides IgG2?

total igG: 7.4

borderline IGM and IGA

 

[Ema]

total igG: 7.4

borderline IGM and IGA

Range?

 

[Marky90]

Range?

IGA was 0.71. Range: 0.70 - 3.7
IGM was 0.49. Range: 0.40 - 2.1

 

[Marky90]

All lymphocyte subsets are a bit low on that test. I am not sure what that would mean. It is probably worth repeating the test another time to see if it is consistent. I doubt that any of these figures are low enough to cause problems in themselves. If your IgG2 is low then maybe there is some more general regulatory shift. I am afraid I cannot say anything very definite.

Thanks prof. The results got me thinking.. Is there anything to do about low t-cell numbers? Or is it probably a consequence of some underlying pathological process? Genetics? Im a little worried about them declining further, as low numbers are seen in many other autoimmune diseases. Don`t need any more^^

 

[Marky90]

Found this: " We found that the CD45RA effector memory CD8+T cell phenotype formed a significantly higher percentage of total CD8+T cells in moderate CFS/ME compared with controls"

http://www.biomedcentral.com/1471-2172/16/35

But it was not in CD4 t-cells, interesting nonetheless..

 

[Marky90]

Sorry to bother you with this @Jonathan Edwards, but I dont have anyone else i know to ask..

found this: http://www.ncbi.nlm.nih.gov/pubmed/23918413
If Rtx also causes t-cell depletion, is it a problem if you`re already somewhat low?

And saw this:

"The use of rituximab to treat autoimmune diseases has provided important clues to the regulatory effects of B cells on cellular immunity. In addition to B cell depletion, rituximab modulates the numbers and functions of peripheral blood lymphocyte subsets such as T, NK, and NKT cells in several autoimmune diseases, including RA, SLE, Evans’ syndrome, and MS (57–61). Rituximab treatment leads to substantial depletion of peripheral T cells, a decrease in the proportion of CD4 cells expressing the early activation marker CD69 and, conversely, an increase of the frequency of CD4+CD25hi regulatory T cells (58, 59, 61)." (
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437032/)

Lastly:
An unexpected and intriguing finding was that CSF Tcells were reduced post-treatment in most subjects, with an overall decrease of 55%. CSF Tcells were reduced by more than 50% in 8/15 (53%) subjects, decreased by lesser degrees in four, and increased in only three subjects, yielding an overall group decrease of more than 55% after treatment. The reason for this reduction is not known. One possibility is that B cells of CNS myelin specificity “home” to the CNS and in so doing alter the blood–brain barrier or secrete chemokines that recruit T cells as well. For example, B cell receptor triggering induces human B cell production of two T cell chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta) and MIP-1 alpha (Krzysiek et al., 1999). Another possibility is that B cells entering the CNS secrete complement-binding Abs which lead to local activation of complement proteins including C5a and C3a. C5a is an especially potent chemo-attractant for monocytes, macrophages and neutrophils, and also upregulates the production of several chemokines by endothelial cells (Sellebjerg et al., 1998; Guo and Ward, 2005).

" (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769354/)

Was t-cell counts ever relevant before giving rtx for RA
If so: can giving IVIG while on rtx lessen the risk for infections?

Thanks (!)

 

[Helen]

TSH 3.8 (0.50-3.6) (over the reference area)

Hi Marky, I would try to get tested for freeT4, freeT3 and thyroid antibodies too. Your elevated TSH is a sign of hypothyroidism and should be investigated further, I think. You may also have a high cholesterol due to hypothyroidism. Old school doctors look at this too. Hypothyroidism, untreated or suboptimally treated, may cause a lot of health issues including an impaired ability to handle infections.

 

[Marky90]

Hi Marky, I would try to get tested for freeT4, freeT3 and thyroid antibodies too. Your elevated TSH is a sign of hypothyroidism and should be investigated further, I think. You may also have a high cholesterol due to hypothyroidism. Old school doctors look at this too. Hypothyroidism, untreated or suboptimally treated, may cause a lot of health issues including an impaired ability to handle infections.

Hi Helen!

Thanks for your reply

I have taken a complete thyroid test two times in one year, so this elevated TSH was the odd one out. Although its been borderline before if i remember correctly. I`ll take a new thyroid test soon to be sure

 

[Marky90]

Is this what i have?

https://en.wikipedia.org/wiki/Idiopathic_CD4+_lymphocytopenia
http://www.uptodate.com/contents/idiopathic-cd4-lymphocytopenia
http://www.bloodjournal.org/content/112/2/287.long?sso-checked=true

 

[Helen]

Hi Helen!

Thanks for your reply

I have taken a complete thyroid test two times in one year, so this elevated TSH was the odd one out. Although its been borderline before if i remember correctly. I`ll take a new thyroid test soon to be sure

I learnt from experienced doctors that even if your numbers are in reference ranges there might be a problem, so if you don´t mind you could post your lab results exactly from the lab reports. Usually we get a message from or doc that "all results were normal" but there might be more information in the numbers. I would study e.g. "stop the thyroid madness", the site or book. I was first recommended this by a doctor!

 

[Jonathan Edwards]

Sorry to bother you with this @Jonathan Edwards, but I dont have anyone else i know to ask..

found this: http://www.ncbi.nlm.nih.gov/pubmed/23918413
If Rtx also causes t-cell depletion, is it a problem if you`re already somewhat low?

And saw this:

"The use of rituximab to treat autoimmune diseases has provided important clues to the regulatory effects of B cells on cellular immunity. In addition to B cell depletion, rituximab modulates the numbers and functions of peripheral blood lymphocyte subsets such as T, NK, and NKT cells in several autoimmune diseases, including RA, SLE, Evans’ syndrome, and MS (57–61). Rituximab treatment leads to substantial depletion of peripheral T cells, a decrease in the proportion of CD4 cells expressing the early activation marker CD69 and, conversely, an increase of the frequency of CD4+CD25hi regulatory T cells (58, 59, 61)." (
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437032/)

Lastly:
An unexpected and intriguing finding was that CSF Tcells were reduced post-treatment in most subjects, with an overall decrease of 55%. CSF Tcells were reduced by more than 50% in 8/15 (53%) subjects, decreased by lesser degrees in four, and increased in only three subjects, yielding an overall group decrease of more than 55% after treatment. The reason for this reduction is not known. One possibility is that B cells of CNS myelin specificity “home” to the CNS and in so doing alter the blood–brain barrier or secrete chemokines that recruit T cells as well. For example, B cell receptor triggering induces human B cell production of two T cell chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta) and MIP-1 alpha (Krzysiek et al., 1999). Another possibility is that B cells entering the CNS secrete complement-binding Abs which lead to local activation of complement proteins including C5a and C3a. C5a is an especially potent chemo-attractant for monocytes, macrophages and neutrophils, and also upregulates the production of several chemokines by endothelial cells (Sellebjerg et al., 1998; Guo and Ward, 2005).

" (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769354/)

Was t-cell counts ever relevant before giving rtx for RA
If so: can giving IVIG while on rtx lessen the risk for infections?

Thanks (!)

I don't know what the first people did to their patients but T cells do not go down with rituximab. Maria Leandro did her PhD on cell chages with rituximab and we studied this over a period of years. Both T and B cell numbers go down temporarily with steroids - and you give steroid with rituximab usually, but the effect on T cells is very short lived.

The second quote seems to be a speculation from a review that makes pretty little sense to me. 'Regulatory B cells' have become fashionable but it is very unclear whether they really exist or if they do which ones they are and what they do.

The third one is about MS I assume and is quite interesting because it confirms our reasoning for considering rituximab for MS way back in 2002. If you remove autoimmune B cells then it seems that you not only stop B cells getting into the brain, but you also stop T cells getting into the brain because there is no longer any inflammation. That can only be a very good thing. You do not want any of either cell in your brain. That has nothing to do with T cell numbers in the places where they are supposed to be.

Almost the entire immunology community works on T cells so they want to prove that rituximab works on T cells so they can have grants on it. But over the fifteen years we have been using rituximab in autoimmunity I have seen no evidence for rituximab reducing T cell numbers or function significantly and lots of evidence that it does not.

 

[Marky90]

I don't know what the first people did to their patients but T cells do not go down with rituximab. Maria Leandro did her PhD on cell chages with rituximab and we studied this over a period of years. Both T and B cell numbers go down temporarily with steroids - and you give steroid with rituximab usually, but the effect on T cells is very short lived.

The second quote seems to be a speculation from a review that makes pretty little sense to me. 'Regulatory B cells' have become fashionable but it is very unclear whether they really exist or if they do which ones they are and what they do.

The third one is about MS I assume and is quite interesting because it confirms our reasoning for considering rituximab for MS way back in 2002. If you remove autoimmune B cells then it seems that you not only stop B cells getting into the brain, but you also stop T cells getting into the brain because there is no longer any inflammation. That can only be a very good thing. You do not want any of either cell in your brain. That has nothing to do with T cell numbers in the places where they are supposed to be.

Almost the entire immunology community works on T cells so they want to prove that rituximab works on T cells so they can have grants on it. But over the fifteen years we have been using rituximab in autoimmunity I have seen no evidence for rituximab reducing T cell numbers or function significantly and lots of evidence that it does not.

Oh my god thank you so much for the feedback prof.. I literally lost all hope today as i need to check if i have this: http://www.bloodjournal.org/content/112/2/287.long?sso-checked=true

And if I would lose t-cells from rtx-treatment, that seemed like a silly thing to do in that context..

Well again thanks a lot for the clarification, I was quite down.

 

[nandixon]

@Marky90, what was your total white blood cell (WBC) count at the time of the results you gave in your original post of Sep 16?

 

[Marky90]

@Marky90, what was your total white blood cell (WBC) count at the time of the results you gave in your original post of Sep 16?

Hi @nandixon !

It was 4.8 (3.5-10.0)

I`m tested for HIV..

So I`m suspecting idiopathic cd4+ lymphocytopenia, which really sucks to have.. But I found out it can be treated with IL-2 and IL-7 succesfully.. At least I potentially found it early, before infections occur, but that depends if its progressive or not. I will have to take another blood test.

Anyways if i I have that, it might have predisposed me for developing ME.

 

[Jonathan Edwards]

Hi @nandixon !

It was 4.8 (3.5-10.0)

I`m tested for HIV..

So I`m suspecting idiopathic cd4+ lymphocytopenia, which really sucks to have.. But I found out it can be treated with IL-2 and IL-7 succesfully.. At least I potentially found it early, before infections occur, but that depends if its progressive or not. I will have to take another blood test.

Anyways if i I have that, it might have predisposed me for developing ME.

Dear Marky90,
You need to get advice from your own immunologist but I don't think you have idiopathic CD4+ lymphocytopenia and you should stop worrying. For starters, all lymphocyte subsets are low to about the same extent. That to me suggests most likely a lab artefact - maybe there was a small clot in the blood sample. And these levels are not the sort of levels I would associate with immune deficiency. In AIDS levels go much lower. I think you should note the lab comment 'this finding has uncertain meaning' which to my mind means they are not very convinced it is significant. There may be some reason why you have lymphopenia in all subsets and there are standard things to look for but idiopathic CD+ lymphocytopenia is about the rarest of all of them. Wait until you get advice from the immunologist.

 

[Marky90]

Dear Marky90,
You need to get advice from your own immunologist but I don't think you have idiopathic CD4+ lymphocytopenia and you should stop worrying. For starters, all lymphocyte subsets are low to about the same extent. That to me suggests most likely a lab artefact - maybe there was a small clot in the blood sample. And these levels are not the sort of levels I would associate with immune deficiency. In AIDS levels go much lower. I think you should note the lab comment 'this finding has uncertain meaning' which to my mind means they are not very convinced it is significant. There may be some reason why you have lymphopenia in all subsets and there are standard things to look for but idiopathic CD+ lymphocytopenia is about the rarest of all of them. Wait until you get advice from the immunologist.

Dear professor,

Thanks again very much for your feedback
Certainly calming.
I`m feeling a bit stupid self diagnosing myself in such a complex field as immunology, being aware of that I have arranged a phone conference with a professor in immunology tomorrow!
I`ll put my loony ideas on hold as suggested.