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B cells and autoimmunity: Is measuring antibody titers reliable when B cells are low?

Inara

Senior Member
Messages
455
Hi everybody,

somewhere in a post (I think by @Pyrrhus) I read that measuring virus titers is unreliable if IgM/IgG/IgA are low.

I wonder if the same applies to low B cells, specifically CD19+ and CD20+ B cells (CD20+ are depleted during Rituximab treatment if I understood correctly, and that suppresses autoimmune activity) with respect to autoimmunity markers. I don't know which antobodies CD19/CD20 produce, but I wondered if

1) there can be autoimmunity but it won't show in lab tests if CD19/CD20 are low,
or
2) having low CD19/CD20 "protects" against (at least certain forms of) autoimmunity, so having low CD19/CD20 can't lead to at least these forms of autoimmunity.

I have low/lowish CD19 and CD20 B cells, but I have Hashimoto's. In the Celltrend panel, two antibodies were positive, so there is some form of autoimmunity, but - as far as I can see it - not really severe. I wondered if autoimmunity lab tests are reliable if B cells are low. Does anybody know?

Thank you!
 

Pyrrhus

Senior Member
Messages
4,172
Location
U.S., Earth
somewhere in a post (I think by @Pyrrhus) I read that measuring virus titers is unreliable if IgM/IgG/IgA are low.

I wonder if the same applies to low B cells

I don't know of research that looks specifically at your question, but I would guess that if your B cells are abnormally low, then your antibody titers may also be abnormally low. In this situation, applying the normal reference range in a specific antibody test may be unreliable for diagnosing any pathology from that specific antibody.

I hope this helps.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
From what I understand, Hashimoto's is T cell driven immunity. Most of the other autoimmunity is driven by B cells, which make antibodies. It makes sense that if your B cells aren't very good at making antibodies, a case of autoimmunity or antibody defense can be missed.

I had 12 doctors miss EBV because I wasn't properly making antibodies. PCR tests, which look for DNA of the viruses are better. As for autoimmune antibodies, if they're low, you might have fewer symptoms.
 

Inara

Senior Member
Messages
455
That's definitely interesting. 🤔 And quite helpful. How can you spot B-cell autoimmunity then? And, if antibodies can't be really produced... how can you have B-cell autoimmunity at all? Or is it just like this:

As for autoimmune antibodies, if they're low, you might have fewer symptoms.

I will read both your posts tomorrow again. I seem to have a low concentration this evening.
 

Gingergrrl

Senior Member
Messages
16,171
@Inara

Did you mean antibody testing for viruses or autoimmune testing for autoantibodies (or both)? Also, did you mean that your B-cells are low (or non existent) from Rituximab, or another B-cell depleting drug, or did you mean that you are testing low for B-cells for some other unknown reason? I wasn't sure if I quite understood what you were asking.
 

Inara

Senior Member
Messages
455
Hi @Gingergrrl

Thank you for asking. You make good points.

I guess every substance that B cells produce and can be measured by a lab could be affected. But in my original post I only meant autoimmune testing for autoantibodies (because I didn't think of the rest).

My B cells are low/lowish due some unknown reason (I think this will get clearer in some weeks). They were not depleted by some drug, like Rituximab.

I just recalled that Rituximab aims at lowering B cells and thus improving symptoms from B cell autoimmunity, and so I wondered if low B cells (e.g. due to some immune deficiency) might lead to mild(er) autoimmunity, or if it might even protect from developping autoimmunity (because there aren't enough B cells that could produce autoantibodies). At least, that's how I understand the replies so far, it can make detecting autoimmunity (or virus antobodies like in @Learner1's case) pretty difficult.
 

Gingergrrl

Senior Member
Messages
16,171
I guess every substance that B cells produce and can be measured by a lab could be affected. But in my original post I only meant autoimmune testing for autoantibodies (because I didn't think of the rest).

@Inara I am sorry for the slow reply and your question makes sense. I would assume (but do not know for sure) that anything produced by B-cells could be affected (both antibodies & autoantibodies) in the scenario that you described.

My B cells are low/lowish due some unknown reason (I think this will get clearer in some weeks). They were not depleted by some drug, like Rituximab.

How did you discover that your B-cells were low? Did you do a test called "Lymphocyte Subset Panel"? This panel might have another name in Germany vs. the US. It measures both the Absolute Number and the Percentages of the different immune cells (CD3, CD4, CD8, NK Cells, and CD19 which are the B-cells). It would tell you what specifically was low although it would NOT tell you why it was low.

I just recalled that Rituximab aims at lowering B cells and thus improving symptoms from B cell autoimmunity, and so I wondered if low B cells (e.g. due to some immune deficiency) might lead to mild(er) autoimmunity, or if it might even protect from developping autoimmunity (because there aren't enough B cells that could produce autoantibodies).

Rituximab kills all of the B-cells so they would not only be low but they would actually be at zero (until they grow back). In my case it took around 8-9 months after my final infusion for them to fully grown back (which we measured using the Lymphocyte Subset Panel and a few other blood tests).

Your second question is interesting and I actually do not know the answer! If I understand right, you are asking if low B-cells (due to an immune deficiency and NOT from a treatment) could lead to milder autoimmunity or even be protective against developing autoimmunity and I don't know the answer. I am hoping that someone else chimes in who does know and I am curious, too.
 

Inara

Senior Member
Messages
455
Thank you @Gingergrrl for your reply! :hug:

How did you discover that your B-cells were low?
Via a lab test (blood sample). Yes, it's a lymphocyte subset panel. The standard panels here don't include CD19/CD20 though, that had to be included manually.
CD19/CD20 wasn't very low or zero, it was at the lower limit and slightly decreased.
 

Shanti1

Administrator
Messages
3,139
there can be autoimmunity but it won't show in lab tests if CD19/CD20 are low
Hi Inara, Have you had or considered having total IgA, IgG and IgG subtypes tested? That might be a more accurate indicator as to if your low B count is actually influencing the accuracy of antibody tests.
 

Shanti1

Administrator
Messages
3,139
Can you explain?
Hi Inara,
Since the main purpose of B-Cells is to produce antibodies, a B-Cell deficiency or poor B-Cell function can result in low levels of total IgA and IgG and/or IgG subtypes.

As an example, a low total IgA can impact the efficacy of antibody testing for celiac disease. In the example below, if the IgA, Quantitative was below the reference, it could call in to question if the negative results for the celiac specific antibodies was accurate.
1661459118718.png


The same can be true for some tests that depend on IgG titers:

https://www.racgp.org.au/afp/2013/april/quantitative-serum-immunoglobulin-tests
Patients with immunoglobulin deficiencies may have false negative results from laboratory tests that measure antibodies in the blood....The impaired antibody responses to pathogens in hypogammaglobulinaemic states may make the serological diagnosis of certain infections, such as HIV and Epstein-Barr virus, difficult. In these patients, nucleic acid detection methods or culture should be performed.

I hope that answers your question!
 

Inara

Senior Member
Messages
455
Hi @Shanti1, thank you very much! I find this very interesting and helpful - so if you have more to read, I'll be interested. :D

In my case CD19/CD20 cells are lowish (low-normal to slightly low), Igg3 subclasses are transiently low,
slightly lowered:
IgA CD27+ memory B cells

low:
IgA CD27- atypical IgA+ memory B cells
IgA CD27- atypical IgG+ memory B cells
IgM+/- CD38++ Plasmablasts... B cells

But total IgA or IgG are normal. sIgA is low in me. (Btw, celiac markers were normal in me when tested - a gut biopsy showed a certain lymphocyte infiltration, that's why I was tested. That's long ago though. And this could make MCAS, too, right?)

So now I would like to understand in detail what the consequences of all of this could be. Like: Ok, this is lowish, this means [this antibody titer] is not reliable and so forth. Like in your example with celiac disease and low IgA.
I will read.

Also, would such B cell "counts" already have consequences symptom-wise?