XLA (CD40, B cells) and XLA vs. CVID

[Guest guest]

Kim (Chris's mom) -- I got your email about the CD40 info, but I don't

know the answer... I will see what I can find out about the CD40 test.

I tend to associate that more with Hyper IgM, but it doesn't sound like

that's what they're looking for in so I'm not sure. I'll let you

know if I find anything. But to answer a different question from one of

your group emails, about B cells --

You wrote:

> " The latest blood work came back saying that he had B-Cells (they tell me the

> reference range is 200-2000 and his were 341) and that although he had no

> antibodies to his immunizations, his t-cells still reacted to tetanus when

> exposed??? He has two Drs. that disagree. The original Dr. still stands by

> the XLA but the Dr. working with him (who is an immunology fellow) says she

> thinks it sounds more like CVID. The question I have is can you have

> B-Cells and still have XLA. "

From what I've read and been taught, the hallmark of XLA is that you do

NOT have B cells (or if you do, it's a VERY low number.... maybe 5-10%

of normal, but certainly not a number that falls in the range of the

normal values). The gene they test for is called " btk " - it stands for

" Bruton's Tyrosine Kinase " - and that gene controls whether a baby B

cell ever develops into a B cell that has surface markers found in

mature B cells (the marker is the CD19 cell surface receptor). That

CD19 marker is what they look for to identify B cells on the test that

he had run (the one in which he had 341 cells, in the normal range), so

if he has a normal number of cells with CD19 on them, I think the

chances of him having XLA are remote. It doesn't mean he doesn't have

agammaglobulinemia (because " agammaglobulinemia " is a descriptive term,

rather than a true diagnosis, and it simply means the absence of Ig's),

but he wouldn't have the X-linked version (Bruton's). It's relatively

uncommon to have a complete absence of ALL Ig's with CVID, but not

unheard of, and it may be that he actually has the capacity to make

*some* Ig's, but he's been chronically infected for so long that the

infections have depleted his reserve, and when he gets on IVIG and stays

healthier, you may see the other Ig levels climb a bit. It's hard to

say... The genetic test is the key, though, to firmly diagnosing

Bruton's, and it makes sense not to worry much about which it is at this

point, just because there's nothing you'd do differently right now,

anyway. The reason to find out if it's Bruton's for the longer term

picture would be:

- if you have sisters that have male children, or will have them, they

will know whether to keep the diagnosis in mind and have them tested

(and treated, if they also are affected) before they get unnecessarily

ill.

- if you plan to have future children, the same thing would apply

- there may be gene therapy and other treatments developed in the next

decade or so, to treat XLA more permanently (and restore capacity to

produce IgA and IgM, whereas now, only the IgG gets replaced by the

IVIG), and I doubt the prospect is as good for CVID to have that type of

treatment within the same period of time.... not that it's impossible

for a genetic-level therapy for CVID to be developed, but just that the

one for XLA will almost certainly come first, because they already know

the gene and what it does (and there's only one gene, whereas CVID is

probably caused by at *least* half a dozen, depending on the clinical picture).

- And finally, in some respects, XLA has a better clinical response to

IVIG than CVID does (if IVIG is started before significant damage is

done by chronic or severe infections). I say that because (with the

exception of a few specific illnesses) XLA patients have problems with

only the humoral (B cell) part of the immune system, and the T cells

tend to work fine, whereas it is believed that in many (most?) cases of

CVID, some sort of T-cell issue underlies the low Ig's. Some of these T

cell problems show up on the standard lymphocyte profiles, and some

don't (but have been described in research settings where scientists do

very specific tests), and still others haven't been shown at all (but

the top CVID experts are coming to believe that there is some cellular

(T-cell) defect underlying the CVID diagnosis, because many CVID

patients have an " incomplete " response to IVIG). BUT, none of that is

set in stone, because some CVID patients do GREAT with IVIG, and some

XLA patients have nagging problems, despite ostensibly having good

cellular (T-cell-based) immunity. One of those rare, nagging problems

is that some XLA patients have trouble containing and completely

eradicating enteroviruses, so they can get a chronic enteroviral

infection that just won't go away, even with high dose IVIG. So, the

comparison I made is not really a completely valid one (that is, you

can't really say that one is better than the other), but I do think that

they have a more complete understanding of XLA, and I think that the

treatments to really achieve long-term, stable health are going to come

about sooner for XLA than for CVID. But that's just a projection, not a

fact.

I hope that helps (and doesn't just confuse the issue more!)... let us

know what you find out about the CD40 test, because now I'm curious!

And of course, let us know about the genetic tests when you have them

done. Welcome to the group!

Take care,