Driving Me Crazy, Gene Questions

[craigiecarter]

Hi all,

I've tried getting this answer over at SillyYaks and by calling EnteroLab themselves. I'd really rather not pay for a $50 consultation with Scot Lewey, but it's driving me nuts.

DD had testing through EnteroLab after her Celiac panel came back with only a high IgG. PCP did not want to repeat, as she suspected the results would again be inconclusive.

Here are her results from EnteroLab: HLA-DQB1 Molecular Analysis, Allele 1 0202

HLA DQB1 Molecular Analysis, Allele 2 0301

Serologic equivalent: HLA DQ 2, 3 (Subtype 2, 7)

Interpretation was that she does not possess either of the main HLA-DQB1 genes predisposing to Celiac, but she's got 2 all over the place!? Because it is 0202 and not 0201, she does not have DQ 2? I'm so confused!?

I just read Scot Lewey's article on Celiac.com, and I'm no better off in that regard, other than being annoyed that EnteroLab doesn't test for DQA genes.

It's really not of the utmost importance, as we will treat her essentially the same. I must admit, that since she's not sensitive to traces of gluten, and she doesn't have the genes for Celiac, my husband and I are not careful about traces and I don't know if we should be, yk? I know that with celiac disease, traces can do damage even if you don't see it, but is this true for Gluten intolerance?

TIA for any information you have. Like I said, this is driving me *nuts*,

Christie

[nora-n]

It is only recently that they have re-classified that variant of DQ2 to less prone to celiac.

You can maybe find my other recent posts about DQ7, how it only differs from the official celiac gene DQ8 by one letter. There are celiac DQ7, and celiac DQ2 (the other kind) (and they now call them 2,2 or 2,5 by the way, we have to get used to the new terminology)

Yes, not having a definite diagnosis is not easy, an much more so if it is your child, let alone what to tell relatives and school etc.

I read some abstracts about the time frame of celiac disease, and they tested relatives of celiac patients. They followed them over many years. What they found is that they first got positive antigiadin tests, and then later progressed to positive antiendomysium or ttg tests. So they concluded that positive antigliadin tests mean very early celiac.

Just google Ford and gluten and you get a lot of answers regarding ttg IgG tests, that he definitely considers them to mean early celiac. Dr. Lewey will just say the same I think.

nora

[craigiecarter]

It is only recently that they have re-classified that variant of DQ2 to less prone to celiac.

You can maybe find my other recent posts about DQ7, how it only differs from the official celiac gene DQ8 by one letter. There are celiac DQ7, and celiac DQ2 (the other kind) (and they now call them 2,2 or 2,5 by the way, we have to get used to the new terminology)

Yes, not having a definite diagnosis is not easy, an much more so if it is your child, let alone what to tell relatives and school etc.

I read some abstracts about the time frame of celiac disease, and they tested relatives of celiac patients. They followed them over many years. What they found is that they first got positive antigiadin tests, and then later progressed to positive antiendomysium or ttg tests. So they concluded that positive antigliadin tests mean very early celiac.

Just google Ford and gluten and you get a lot of answers regarding ttg IgG tests, that he definitely considers them to mean early celiac. Dr. Lewey will just say the same I think.

nora

First of all, thank you, thank you, thank you. I have no idea why since I'm not totally new to the idea of Gluten intolerance/celiac disease for my family, but I still find it very overwhelming and lonely.

That said, I'm sorry, but I'm still lost. I meant to ask this before. She is 2, 3, Subtype 2, 7. So she has the no longer considered celiac gene, 0202, and 0301, where the heck does the 7 come from (I'm not clear on why there are 4 numbers)? I've tried to make heads or tales of the wikipedia pages, and boy, that's tough for my non-scientific mind. Is she DQ 2, DQ 3 or DQ 2, DQ 7, of which 7 is part of 3?

I gather that DQ 7 is a variant of DQ 3?, which is perhaps what you are referring to above when you say "celiac DQ 7"

I will attempt to read your other posts when I am more fresh. Being gluten-free has so far done nothing for my exhaustion, but as I am nursing DS2, I will remain gluten-free until he weans, which will most likely not be for quite some time.

Thank you for your empathy about the need to know. I haven't gotten to the possibility of her rebelling in my head, though I know it is more than possible, especially since she has long been a mini-teenager, lol.

As for Dr. Ford and his thoughts on IgG being an early indicator, I had printed one of his articles and used it to try to get BCBS to pay for the EnteroLab testing, which was unsuccessful. It was still worth it to me (TG we have the means), but I am not eager to pay for testing for the rest of us, though we should, I imagine. That would be almost an additional $1500 and I don't have that laying around!

I did multiple appeals with BCBS and they kept saying that Fine has not published his findings and that it is not SOP for gastroenterologists. Well, yes, the ped. gastro. was more than happy to disregard my concerns about her symptoms and write off the high IgG. I still had a child who was suffering. Grr. Sorry for the rant.

As you can see, I am trying to figure out how to proceed with the rest of the family. DS2 is most definitely gluten intolerant, but as he is nursing, EnteroLab recommends not testing him yet, but I've now heard that they also claim that the results can be less accurate if he is gluten free. So, it looks like we will be crossing a very unpleasant bridge in a couple of years when he decides to wean.

If you could, I'd love any info about my confusion regarding the 4 numbers. Every time I read something on wiki or what have you, I come away with a little more understanding (I think), and a lot more confusion!!!!

TIA,

Christie

[mftnchn]

We each have 2 genes and each has two alleles. As you said Enterolab just tests the B alleles. Hence only two numbers. So the 2,2 and 2,5 will reflect all four alleles. But your 2, 3 just reflects two of them. The DQ7 comes from the subtype designation.

The confusion comes with the change of labeling. The DQ2 with the subtype of 2 means it is less connected to celiac than is the subtype 1. The DQ7 I think comes from the 3 subtype 7. Since a lot of the information uses the DQ2 and DQ7, search on those but be aware that you don't have the usual DQ2 celiac connection. I have two of the DQ2 subtype 1 genes so have the highest possible risk for celiac.

[craigiecarter]

Oh, I forgot to mention that her TtG was elevated as well, which from my limited understanding, indicates intestinal damage, which would mean Celiac Disease.

I have been reading about this on an off for 3 years, and it still makes my head spin! Am I totally off base?

Thanks again,

Christie

[mftnchn]

Christie, the ttg is even more specific for celiac because it tests for the enzyme the body produces that causes the intestinal damage.

Your Enterolab results are very positive--I'd take that seriously, along with a positive blood test.

Traces can make a differene to anyone but seems like some people are less bothered.

My allergist told me at the outset of going gluten-free to be as absolutely strict as I can. He said that I would only know over time how sensitive I am.

Also, many have reported here that after going gluten-free they become more sensitive to small amounts of gluten. I did see one person report that after several years that tapered off again.

Bottom line, you don't know how it will be for your daughter. If she still has any symptoms, you likely need to be stricter and for a good long period of time before you will know.

[nora-n]

DQ1 has subtypes 5 and 6,

DQ2 can be made up several ways, 2,5 is the mst common and 2,7 is over two genes and 2,2 is the less prone gene as far as I remember.

On 2,7 you have to read the wiki on DR , and other things, to understand.

DQ3 has 7, 8 and 9 as subtypes. They vary just by one little letter, they are very similar and there are reported celiacs with DQ7 and 9 too, not just 8.

And, the DQ explains only roughly half of the celiac thing, there is also this MYO9B (spelling?) and the cytokine thing, I will have to lokk it up in my notes, but maybe it is easy to find in pubmed, another gene variant that makes us more prone to celiac.

Maybe she only has gluten-sensitive genes but the full load of the other things.

In my opinion, if the ttg is elevated, this points to definite villi damage visible in biopsies as this ttg test is very specific.

Added: Yes, pubmed brings up cytokines, namely TNFa as a risk factor for celiac, besides DQ genes.

Here is just one of the abstracts, look to the right there for more Open Original Shared Link

nora

[ShayFL]

And dont forget the most conclusive test of all = POSITIVE RESPONSE TO THE DIET.

[craigiecarter]

We each have 2 genes and each has two alleles. As you said Enterolab just tests the B alleles. Hence only two numbers. So the 2,2 and 2,5 will reflect all four alleles. But your 2, 3 just reflects two of them. The DQ7 comes from the subtype designation.

The confusion comes with the change of labeling. The DQ2 with the subtype of 2 means it is less connected to celiac than is the subtype 1. The DQ7 I think comes from the 3 subtype 7. Since a lot of the information uses the DQ2 and DQ7, search on those but be aware that you don't have the usual DQ2 celiac connection. I have two of the DQ2 subtype 1 genes so have the highest possible risk for celiac.

Eureka, I think I've got it!!!! So, she's DQ 2, subtype 2 (the one less associated with Celiac) and DQ 3, Subtype 7, also not directly connected to Celiac?

So although there are 4 numbers, they are still only associated with the 2 B alleles?

Thanks!!!

Christie, still surprised at how much it bothers me not to understand something!

[nora-n]

Eureka, I think I've got it!!!! So, she's DQ 2, subtype 2 (the one less associated with Celiac) and DQ 3, Subtype 7, also not directly connected to Celiac?

So although there are 4 numbers, they are still only associated with the 2 B alleles?

Thanks!!!

Christie, still surprised at how much it bothers me not to understand something!

Yes, this just means DQ2 and DQ7, the less prone DQ2 and the only gluten-sensitive DQ7. But, it is possibe to be celiac anyway, and there are officially diagnosed Dq7 in the literature, just check my postings.

According to this wiki, there are some other rare DQ2 as well beside the three main DQ2 (the DR3 one, the main celiac DQ2, nicknamed 2,5, and the less celiacm prone 2,2, and the 2,3 Open Original Shared Link

it even spells out the DQB1 being 0202 , the less celiac prone gene if without DQ7.

See also wiki on HLA-DR and DQ .

Also mistyping does occur. The wikis keep mentioning mistyping, yet doctors often misunderstand test results and say that non-DQ2 or 8 mean the person canot possibly be celiac. This is not true, but the chances are smaller......and, mistyping occurs, see the DQ2 wiki that some test kits say it is 0201 when it really is 0202.

And, there is a transhaplotype of DQ2, is it well known that in the case of 2,2 and 7,5 they form Dq2,5 across the genes, meaning that the combination your daughter has, probably makes up 2,5 anyway. There are even drawings of this trans-DQ2 on the net. http://www.tidsskriftet.no/lts-img/2003/L03-22-Med-19-01.webp

funnily enough there are even DQB1 0303 who actually are a kind of DQ2 according to the DQ2 wiki, but I think enterolab just reports them as DQ9......yes, gene tests can be more confusing than they seem to be on first glance.

LIke, the genes are only the second highest risk: "DQ2 represents the second highest risk factor for coeliac disease, the highest risk is a close family member with disease" from the wiki page on DQ2.....doctors often misunderstand what the gene tests really mean.

But, in your case it means daughter is DQ2,5 anyway because it is formed in trans with 2,2 and 7,5. The enterolab and other tests do not say that.

nora

[fedora]

hi,

this is basically a repeat of what Nora was just saying.

The two main celiac genes are DQ2.5 and DQ8. DQ2.5 can be the whole gene DQ2 subtype 1 OR it can be made up of two genes. DQ2.2(that is subtype 2) AND SOME of the DQ7 genes.

SO your daughter may have the full DQ2.5 gene. The thing is Enterolab does not explain that. Which is really irratating because then it leaves people with DQ2.2 and DQ7 thinking they don't have the gene. The only way to know if the DQ7 gene your daughter has is the correct half of the full celiac gene DQ2.5 is to have the alpha part of the gene tested also.

Also there are documented cases of people with only DQ2.2 having celiac. It has also been proven to cause a reaction to gluten in people without always passing the threshold to cause celiac disease. There have been documented cases of people with celiac with only the DQ7 half of the gene.

One study found of the celiacs studied 94% had DQ2.5 or DQ8. 4%had DQ2.2 only and 2% had DQ7(the particular one needed to complete the gene) only.

By the way, what were her results? Shame on your dr. A high ttg is something for sure.

I suspect she has the whole gene.

I have only the DQ2.2 gene and was sick on and off for years. NO one can convince me it is not enough to make someone very ill. I got lucky cause at 19 I was diagnosed with a wheat allergy which saved me some suffering for the next 12 years.

take care

[craigiecarter]

The two main celiac genes are DQ2.5 and DQ8. DQ2.5 can be the whole gene DQ2 subtype 1 OR it can be made up of two genes. DQ2.2(that is subtype 2) AND SOME of the DQ7 genes.

SO your daughter may have the full DQ2.5 gene. The thing is Enterolab does not explain that. Which is really irratating because then it leaves people with DQ2.2 and DQ7 thinking they don't have the gene. The only way to know if the DQ7 gene your daughter has is the correct half of the full celiac gene DQ2.5 is to have the alpha part of the gene tested also.

That is irritating!!! Thankfully I've been hanging around enough to know that gluten intolerance is not something to be written off. Our PCP, though supportive and very natural minded, including admitting that gluten really isn't good for anyone, suggested that we "play around" with gluten to see how much she could tolerate. I was not comfortable with that, b/c I just don't feel confident that gluten does not do damage to someone with gluten intolerance, yk? Plus, I've always had this niggling feeling that she does have Celiac.

Also there are documented cases of people with only DQ2.2 having celiac. It has also been proven to cause a reaction to gluten in people without always passing the threshold to cause celiac disease. There have been documented cases of people with celiac with only the DQ7 half of the gene.

One study found of the celiacs studied 94% had DQ2.5 or DQ8. 4%had DQ2.2 only and 2% had DQ7(the particular one needed to complete the gene) only.

By the way, what were her results? Shame on your dr. A high ttg is something for sure.

I suspect she has the whole gene.

I have only the DQ2.2 gene and was sick on and off for years. NO one can convince me it is not enough to make someone very ill. I got lucky cause at 19 I was diagnosed with a wheat allergy which saved me some suffering for the next 12 years.

Here Celiac Panel results from 3 years ago, indicated a high IgG (91, when 19 was the high end of normal). She was about 2. NP we used to see initially freaked and said that she had Celiac, then consulted a ped. gastro who told her to run a sed. rate and if that was fine, that it was a false positive. I pursued it, took her to a ped. gastro myself, who came close to laughing us out of his office. Her symptoms were infrequent enough that I hesitantly ignored them for a time, until my son was born and started exhibiting the same symptoms. Our current FP has been supportive, though, I think a bit uneducated based on her recommendation to play around with gluten amounts. Nonetheless, she jumped through some hoops to get the EnteroLab testing paid for by BCBS (unsuccessful, but....).

The high TtG was via EnteroLab which, of course, mainstream medicine disregards.

I have to read what you all wrote more thoroughly, but it sounds like she could indeed be Celiac and either way, I should be more careful about traces to allow her to heal and then she may be able to tolerate traces, but I should still avoid them.

I'm still hoping that my brain can wrap my head around the gene stuff, just b/c I'm a sleuth, but it's not promising considering that I had an awful time just finding this thread on the forum

Thank you so much!!!

[craigiecarter]

Yes, this just means DQ2 and DQ7, the less prone DQ2 and the only gluten-sensitive DQ7. But, it is possibe to be celiac anyway, and there are officially diagnosed Dq7 in the literature, just check my postings.

According to this wiki, there are some other rare DQ2 as well beside the three main DQ2 (the DR3 one, the main celiac DQ2, nicknamed 2,5, and the less celiacm prone 2,2, and the 2,3 Open Original Shared Link

it even spells out the DQB1 being 0202 , the less celiac prone gene if without DQ7.

See also wiki on HLA-DR and DQ .

Also mistyping does occur. The wikis keep mentioning mistyping, yet doctors often misunderstand test results and say that non-DQ2 or 8 mean the person canot possibly be celiac. This is not true, but the chances are smaller......and, mistyping occurs, see the DQ2 wiki that some test kits say it is 0201 when it really is 0202.

And, there is a transhaplotype of DQ2, is it well known that in the case of 2,2 and 7,5 they form Dq2,5 across the genes, meaning that the combination your daughter has, probably makes up 2,5 anyway. There are even drawings of this trans-DQ2 on the net. http://www.tidsskriftet.no/lts-img/2003/L03-22-Med-19-01.webp

funnily enough there are even DQB1 0303 who actually are a kind of DQ2 according to the DQ2 wiki, but I think enterolab just reports them as DQ9......yes, gene tests can be more confusing than they seem to be on first glance.

LIke, the genes are only the second highest risk: "DQ2 represents the second highest risk factor for coeliac disease, the highest risk is a close family member with disease" from the wiki page on DQ2.....doctors often misunderstand what the gene tests really mean.

But, in your case it means daughter is DQ2,5 anyway because it is formed in trans with 2,2 and 7,5. The enterolab and other tests do not say that.

nora

[craigiecarter]

Yes, this just means DQ2 and DQ7, the less prone DQ2 and the only gluten-sensitive DQ7. But, it is possibe to be celiac anyway, and there are officially diagnosed Dq7 in the literature, just check my postings.

According to this wiki, there are some other rare DQ2 as well beside the three main DQ2 (the DR3 one, the main celiac DQ2, nicknamed 2,5, and the less celiacm prone 2,2, and the 2,3 Open Original Shared Link

it even spells out the DQB1 being 0202 , the less celiac prone gene if without DQ7.

See also wiki on HLA-DR and DQ .

Also mistyping does occur. The wikis keep mentioning mistyping, yet doctors often misunderstand test results and say that non-DQ2 or 8 mean the person canot possibly be celiac. This is not true, but the chances are smaller......and, mistyping occurs, see the DQ2 wiki that some test kits say it is 0201 when it really is 0202.

And, there is a transhaplotype of DQ2, is it well known that in the case of 2,2 and 7,5 they form Dq2,5 across the genes, meaning that the combination your daughter has, probably makes up 2,5 anyway. There are even drawings of this trans-DQ2 on the net. http://www.tidsskriftet.no/lts-img/2003/L03-22-Med-19-01.webp

Hi all,

It's been a while since I've been here--busy cooking Gluten-free Casein-free and trying to figure out if the kids have more food intolerances. At any rate, people with potential gluten issues are popping up everywhere in my life, and today, in searching for information on which labs test for both Alpha and Beta chains of DQ2 (so an online friend doesn't have my same frustration), I came across this (link on the bottom):

In addition, the HLA-DQ2 molecule can be constructed

from the alpha and beta chain of either of the parentally inherited

genes. Thus, DQA1*0501 and DQB1*0201, encoded either

in cis or trans on the sixth chromosome, can form the DQ2

(DQA1*0501, DQB1*0201) molecule. This is an important

concept because individuals with HLA-DR5 (DQA1*0501,

DQB1*0301) on one chromosome and DR7 (DQA1*0201,

DQB1*0202) can form DQ2 (as DQA1*0501, DQB1*0202)

[nora-n]

There was a posting here not so long ago , a man phoned labcorp about the gene test, and they even told him what alpha chains he had.

Looks like they know all that, but when reporting on celiac gene tests they first just answer positive or negative for DQ2 or DQ8....

https://www.celiac.com/gluten-free/index.ph...15&start=15 check posting nr 18 :

"The lab didn't give me a DR type on the results, they gave me a negative/positive for DQ2/DQ8 only. Labcorp (where I had the test done) doesn't report the alleles on the 'doctor' form - they just said I was DQ8 positive... so I called the HLA testing lab (they provide a contact number) and the woman there said they do the full allele set and was more than happy to provide me my alpha and beta units for both alleles. She said they use very sensitive testing and are fairly accurate. The lab which does this also does HLA tests for organ transplants, DNA testing for paternity, etc. It was the Labcorp HLA lab in Burlington NC that did the testing. The DR subtype I got on the internet comparing my set of alpha/beta to those that are in the DR4 gene type. I COULD be DR8 as well if the testing incorrectly marked my 0302 alpha chains....

However, given I have a very rare cardiac defect at birth (which would be more prevalent in a DR4/DR4 homozygote) I tend to believe the numbers are accurate. My cardiologist said that with the rare cardiac defect at birth, in other patients with similar symptoms, he's been finding undiagnosed celiac after having to undergo valve replacement surgery for aortic stenosis - which is one of the problems associated with the DR4 gene set! (I have a bicuspid aortic valve - which is NOT very common to have this!)

"

Sounds like some labs do know more but do not tell you.....

If you read more postings in that thread, there is someone who was told she had half a celiac gene, and I do not recall anyone else reporting half a gene.

But if one checks out how many do have half a gene, it is 6% (in the cited European study of 1008 celiacs) so we should have 6% reporting here they are celiacs with half the gene. But, only one came and reported that. So I think that they are just told they are DQ2 and 8 negative....

Also, Dr. Scot Lewey (www.thefooddoc.com) wrote on his webpage that he had two patients with positive biopsies but negative gene tests, and he suspected those with the half genes are not reported.

And, still, there are 0202 DQ2 celiacs out there, read the wikipedia on that, the difference is that they are a bit less prone to celiac.

(unless they have the 05* from the DQ7, then they of course are trans DQ2 and that means celiac gene. 0301 reads DQ7 but not all have the 05* but it is most likely)

nora