A bit of a "nerdy" question...

[debs24]

Hi all

I was looking through my blood test results recently and was dabbling in a little online research on all the various "CD" numbers shown on the flow cytometry report (OK...I know...I'm a bit of a nerd...!).

When I got round to checking out CD23, I noticed a lot of online references to "soluble CD23" (sCD23) so, I am curious to know whether CD23 is the same thing as sCD23 and, if not, can anyone please explain the difference to me (in simple terms, ideally....I never said I was a clever nerd...!)?

Thanks.

Debs.

[AussieNeil Administrator]

Debs, as you'd be aware, CD markers (Clusters of Differentiation) are just a range of different proteins on a cell membrane that can be used to tell the different types of body cells apart in a process called immunophenotyping: en.wikipedia.org/wiki/Clust...

Basically, while every cell in our body starts from identical DNA that we inherit from our parents, as the cells differentiate to perform different functions in the body (e.g the different blood cell types, liver cells, kidney cells, skin cells and so on), that differentiation is reflected in the specific CD's observed on the cell's surface membrane. Soluble CD23 just means that the CD23 cluster is also soluble in blood plasma - it doesn't necessarily stay attached to the cell's surface. So CD23 can exist in two forms membrane CD23 and soluble CD23 (mCD23 and SCD23 respectively).

This paper explains how research determined that it's the changing concentration of sCD23 derived from the mCD23 that regulates Immunoglobulin E (IgE) production by the B-cell:

ncbi.nlm.nih.gov/pubmed/223...

And here's the simpler Wikipedia article:

en.wikipedia.org/wiki/CD23

(You'll note in that article that it states that CD23 "is found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets". Incidentally, that's probably why we don't have a successful CD23 antibody like Rituximab (a CD20 clonal antibody) to use against CLL. as it would target those other body cells. (For more on this see ThreeW's reply below.)

You may have even come across the paper below, which notes that sCD23 levels are higher in CLL patients and the serum level can be used as a prognostic marker!

bloodjournal.org/content/bl...

From another nerd, who didn't know the above without reading further, so thanks for raising that interesting topic. Fascinating, isn't it!

Neil

[debs24 in reply to AussieNeil]

Thanks very much, Neil.

I'll definitely check out the links you suggest!

I, along with many more CLLers (I presume...), have CD23++ showing up on my cells and I have, indeed, seen the paper you refer to (the one that suggests high levels of sCD23 can be used as a prognostic marker). In fact, this was the prompt for my original question - I was trying to find out whether my CD23++ is a prognostic marker or does the (possible) prognostic capability only apply to sCD23?

And you are so right....although I'd rather not be researching CLL from a patient's perspective, I can't help but be fascinated by it all! (and I'm also happy to know it's not just me who finds this stuff interesting...!😉)

Thanks very much for the info. - much appreciated (as are all your contributions on this site!).☺

Debs.

[AussieNeil Administrator in reply to debs24]

Hi Debs,

Firstly, I hope you've read the extra information provided by ThreeWs - there is an (unsuccessful) CD23 monoclonal antibody!

With regard to your question about the value of CD23 expression on B-CLL cells (mCD23) as a prognostic marker, I think this paragraph in the conclusion of that interesting research paper answers your question: "Of interest, the expression of membrane CD23 on CD5+ B cells from CLL patients has been previously related to survival by Geisler et al,” who reported a favorable outcome for patients with high membrane CD23 expression compared with cases with low CD23 expression. An inverse relationship between membrane CD23 expression and disease activity was not confirmed by other recent studies. These controversial data may be explained by the difficulty in assessing quantitatively surface CD23 expression by flow cytometry due to the unstability of the CD23 molecule, which is rapidly cleaved from the cell surface into stable soluble CD23. In contrast, the measurement of soluble CD23 has been shown to be a highly reproducible and quantitative method."

Further, that paper was published in 1996, so the research is about 20 years old. I'd say that the fact that sCD23 has not been adopted as a prognostic marker and that 20 years on we are still seeing papers proposing new prognostic markers says it all.

It seems that we are still a long way from being able to predict the progression of a specific CLL patient based on recognised prognostic markers, with the possible exception of more serious markers such as TP53/del(17p). We can reasonably predict the prognosis of a group CLL patients with particular prognostic markers, but there is still a wide distribution, which I think is great, because it gives all of us hope, even if we find we have some markers that correlate with a poor outcome.

Neil

[debs24 in reply to AussieNeil]

Good morning (or whatever time of day/night it is with you)! 🌞🌛

Thanks to both you and to ThreeWs for yet more valuable information.

Very interesting to read about Lumiliximab (a new name to me!), and its disappointing results...not surprising that this hasn't progressed much looking at the reasons spelled out by ThreeWs.

Thanks for your explanation as to why sCD23/CD23 are unreliable prognostic indicators - I guess there are plenty of other indicators currently proving their worth, though.

Your wise comments about prognostic indicators simply being applicable to groups of patients (as opposed to individuals), and the very "individual" nature of our own CLL, suggests there may be some value in us knowing "enough" about our personal situation/markers, but also remaining aware that we can't assume anything for certain!

You also make a good point about keeping an eye on the date that research papers were produced. A paper doesn't need to be very old for it to be out-of-date in these times of very fast moving progress, especially in the field of CLL, etc....which has got to be a real positive!

Still, I think there are some very clever people out there spending a lot of time working to advance our understanding of this condition. The number of new developments over just the last couple of years is astonishing! And it doesn't look as though things are slowing down. ..in fact, much the opposite!😊

I think there are lots of reasons for us CLLers to feel positive and optimistic for the future.

Hang in there, everyone!

Things can only get better☺

Have a great day.

Debs.

[ThreeWs in reply to AussieNeil]

Hi Neil,

Overall a great reply to Debs24's question from which I learned new things but regarding your statement "Incidentally, that's why we don't have a CD23 antibody like Rituximab (a CD20 clonal antibody) to use against CLL as it would target those other body cells. " We actually have been playing with a CD23 mAb for quite a few years now called Lumiliximab. Lumi has not been a great hit however.

In fact the high incidence of side effects may well be because it is expressed on many of the other functioning immune cells you listed.

goo.gl/vdHnCp

I agree the complexity and interactive dynamics of our immune systems not to mention our exploration of them is fascinating. I would question the use of resources on a mAb like Lumi after so many years (since 2009) of disappointing results from multiple Clinical Trials.

WWW

[AussieNeil Administrator in reply to ThreeWs]

Thanks for the correction WWW; I've updated my reply and learnt even more!

Neil