Could Someone Please Help With My Genetic Tests, Too?

[Gardening]

Could someone please help with the significance of these results?

Mine:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0603

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

Older daughter:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0202

Serologic equivalent: HLA-DQ 2,2 (Subtype 2,2)

Younger daughter:

HLA-DQB1 Molecular analysis, Allele 1 0202

HLA-DQB1 Molecular analysis, Allele 2 0603

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

I tried looking at other posts and the Wiki entry for HLA-DQ, and I still can't translate. I don't even see a subtype 2.6 in wikipedia.

Enterolab said I have a celiac gene and a "gluten sensitive gene" and my younger daughter just has two "gluten sensitive genes" and yet we have the same serologic equivalent? I am totally confused.

Thank you in advance for your help!

[Skylark]

Enterolab took me a while to figure out too. The serologic equivalent Enterolab is talking about is from old blood tests, not genetic tests. It used to be that we couldn't tell that there was more than one gene for DQ1 tissue typing. Once the HLA-DQ gene testing was invented, all the various genes that give a DQ1 reaction in organ transplant tests were divided up into DQ5 and DQ6. The "subtype" on the Enterolab listing refers to the beta-chain on Wikipedia, and the last bit, the 0201, 0202 is the most modern designation for the specific beta chain allele. That bit carries the most detail. Sadly, Enterolab does not test the alpha chains.

So, you are DQ2 and DQ6, with the 0201 and 0603 alleles. Your older daughter is double DQ2, with the 0201 from you and 0202 from your husband. Your younger daughter is also DQ2 and DQ6, with the 0202 from your husband and 0603 from you. Your husband must have at least one copy of 0202, and we can't say anything about his other allele.

The 0201 allele is often inherited along with 0501 alpha, and makes DQ2.5, a protein that is well studied and perhaps the highest risk for celiac. You can't be 100% sure you're DQ2.5 as the alpha chain wasn't tested. The 0202 that your husband and younger daughter have is also associated with celiac, although less strongly. Enterolab is probably calling 0202 "gluten sensitive" and 0201 "celiac".

[Gardening]

Skylark, yes, that is helpful, thank you. You are right, Enterolab is calling 0201 the celiac gene and 0202 the sensitive one.

Does the fact that my older daughter is a double DQ2 have any significance? Or not, because it wouldn't be double DQ2.5? I am so annoyed with myself that she was gluten-lite for three weeks and then gluten free for 10 days before the test.

It was my younger daughter who did not have the 0201 who had the pos TTG on the Enterolab test - obviously, genetics aren't everything.

I do have diagnosed celiac in my family (great-aunt), with quite a lot of "celiac-associated" issues in that same strand of the family (mental illness, including bipolar, osteoporosis (every.single.woman.), arthritis, migraines). I want to be able to go to my mom with as complete a picture as possible, kwim?

[Skylark]

As you note, the genes and TTG are not tracking in your family. HLA-DQ simply isn't the whole story with celiac.

The way HLA-DQ works, you make all your alpha and beta chains in all combinations. Only 1/4 of your own HLA-DQ molecules might be DQ2.5. We don't know what your alpha chains actually are but you're reasonably likely to be DQ6.3 and DQ2.5. If so, you would make a mix of DQ2.5, DQ6.3, DQ2.3, and DQ6.5.

Your older daughter has two DQ2 alleles so she only makes DQ2.2 and DQ2.5. Half her HLA-DQ molecules are DQ2.5. That means based on current research/thinking her immune system is a little more likely to identify gliadin as an antigen than yours or your younger daughter. Someone with double DQ2.5 makes no other HLA-DQ molecules and they seem to have a very high chance of eventually identifying gliadin as an antigen and developing celiac.

Again, there are serious holes in the HLA-DQ genetic model, so take everything I say with a grain of salt. It is based on current peer-reviewed literature and scientists are well aware that the genetics are woefully incomplete. Your younger daughter obviously has something going on, even though her risk for celiac would be lower by the HLA-DQ model.

By the way, when I saw Markku Maki talk, he said that an awful lot of people with DQ2.5 feel healthier off gluten even if they are not celiac.

[Gardening]

Ugh. Well, I just read the celiac panel results myself - which my nutritionist (who is hereby fired) had told me was all normal. My older daughter tested out normal on everything, except that her total IGA was only 21. The ref range was 27-195.

Which, 1. makes me wonder what her 22 AGA IGA on Enterolab could have been with normal total IGA and 2. what all is going on with her (she scored very low on a vitamin/mineral panel).

On a positive note, the pediatric GI who works with Dr Fasano is going to see my little one in two weeks!

Thank you again for your expertise!

[ravenwoodglass]

Ugh. Well, I just read the celiac panel results myself - which my nutritionist (who is hereby fired) had told me was all normal. My older daughter tested out normal on everything, except that her total IGA was only 21. The ref range was 27-195.

Which, 1. makes me wonder what her 22 AGA IGA on Enterolab could have been with normal total IGA and 2. what all is going on with her (she scored very low on a vitamin/mineral panel).

On a positive note, the pediatric GI who works with Dr Fasano is going to see my little one in two weeks!

Thank you again for your expertise!

I am glad she is being seen soon. Make sure you keep her on gluten until all testing is done. After the tests do give the diet a good strict try for everyone.

[Skylark]

Ugh. Well, I just read the celiac panel results myself - which my nutritionist (who is hereby fired) had told me was all normal. My older daughter tested out normal on everything, except that her total IGA was only 21. The ref range was 27-195.

Which, 1. makes me wonder what her 22 AGA IGA on Enterolab could have been with normal total IGA and 2. what all is going on with her (she scored very low on a vitamin/mineral panel).

On a positive note, the pediatric GI who works with Dr Fasano is going to see my little one in two weeks!

Thank you again for your expertise!

You're welcome for the help.

That was flat-out malpractice from the nutritionist. If someone referred you to that nutritionist, they should be made aware of it.

Of course her tests are normal if she's IgA deficient. And no, she won't show much fecal IgA either so I agree the 22 on Enterolab is interesting. IgA deficiency is another risk factor for celiac so she's got two now with the DQ2.5. To get a diagnosis, you'd have to gluten her up along with the little one and test her anti-gliadin and anti-TTG IgG and probably get a biopsy.

[Gardening]

The GI is now going to see my older daughter, too.

I really, really hate to re-gluten her, though.

1. Many of her symptoms are psychological and impact her ability to "succeed" in preschool (playing with other children, etc). Her preschool teachers have voiced concerns each year. it also makes for an incredibly stressful home life.

2. She understands that she is "allergic" to wheat and cannot have gluten in any form. This was based on an off-the-charts IGG to wheat and a high IGG to gluten back in May. She is very careful and compliant. I have a hard time explaining to her that it is very, very bad for her to eat gluten, ever, no exceptions, and simultaneously make her eat it daily for two months. I'm afraid that disconnect would come back to bite me when she is a rebellious teen.

3. Knowing how deficient her vitamins were, I hate to prolong her healing. She has been gluten-lite for 3 weeks and gluten free for five weeks now. My husband and I are so ready for things to turn a corner, and we were hoping to start out the school year on the right foot.

Plus, what if I do re-gluten her, and then the biopsy is (rightly or wrongly) negative?

[ravenwoodglass]

The GI is now going to see my older daughter, too.

I really, really hate to re-gluten her, though.

1. Many of her symptoms are psychological and impact her ability to "succeed" in preschool (playing with other children, etc). Her preschool teachers have voiced concerns each year. it also makes for an incredibly stressful home life.

2. She understands that she is "allergic" to wheat and cannot have gluten in any form. This was based on an off-the-charts IGG to wheat and a high IGG to gluten back in May. She is very careful and compliant. I have a hard time explaining to her that it is very, very bad for her to eat gluten, ever, no exceptions, and simultaneously make her eat it daily for two months. I'm afraid that disconnect would come back to bite me when she is a rebellious teen.

3. Knowing how deficient her vitamins were, I hate to prolong her healing. She has been gluten-lite for 3 weeks and gluten free for five weeks now. My husband and I are so ready for things to turn a corner, and we were hoping to start out the school year on the right foot.

Plus, what if I do re-gluten her, and then the biopsy is (rightly or wrongly) negative?

I would be reluctant to have her do a gluten challenge also. You may want to do the first visit with copies of her tests and medical records in hand including growth charts if she has fallen down in growth rate, detailed info about her symptoms and if her playschool teachers have seen a difference in her since she started the diet and/or observed her reactions if she has been accidentally glutened that might be helpful also. You can then take it from there. If there are other family members already diagnosed your GI may not see a need for a challenge for diagnosis.

[Skylark]

The GI is now going to see my older daughter, too.

I really, really hate to re-gluten her, though.

1. Many of her symptoms are psychological and impact her ability to "succeed" in preschool (playing with other children, etc). Her preschool teachers have voiced concerns each year. it also makes for an incredibly stressful home life.

2. She understands that she is "allergic" to wheat and cannot have gluten in any form. This was based on an off-the-charts IGG to wheat and a high IGG to gluten back in May. She is very careful and compliant. I have a hard time explaining to her that it is very, very bad for her to eat gluten, ever, no exceptions, and simultaneously make her eat it daily for two months. I'm afraid that disconnect would come back to bite me when she is a rebellious teen.

3. Knowing how deficient her vitamins were, I hate to prolong her healing. She has been gluten-lite for 3 weeks and gluten free for five weeks now. My husband and I are so ready for things to turn a corner, and we were hoping to start out the school year on the right foot.

Plus, what if I do re-gluten her, and then the biopsy is (rightly or wrongly) negative?

She had a high IgG to gluten? In someone with low IgA, that's one of the signs of celiac. The other antibody would be anti-TTG IgG. It's such a shame they didn't get the testing right.

My understanding is that there are school situations where a doctors' note is helpful. Perhaps one of your doctors is willing to write what is necessary based on the results you have so far, her multiple risk factors, and a positive result to a gluten-free diet. I did not re-gluten myself for tests, and I completely understand your reluctance to deliberately make your daughter sick and confuse her.

[Gardening]

I know, so backwards. Sigh.

She is not autistic, but has many of the co-morbidities, so we were doing biomedical/DAN testing with a nutritionist. IGG testing to different foods is part of the protocal. It was in researching the significance of the IGG results (since it's a controversial test among allergists) that I stumbled across the celiac panel information, and in digging further, started to wonder about celiac (esp. since it is in my family).

Her celiac panel did include AGA IGG and TTG IGG. At least the panel was a good one. But everything was negative - I thought IGG took a lot longer to go down? But yes, everything was negative (with low total IGA).

My nutritionist just called me with more test results (I'll receive them tomorrow in the mail and review them myself, obviously!). It was the CBC and serum cortisol. Her cortisol was low and her CBC showed macrocytic anemia. Initial searching shows that macrocytic anemia can be from B12 or folate deficiency. She had both (and B12 was especially low).

I'm ready for this mystery to be solved! I'm glad an experienced specialist will be reviewing all her labwork, and hopefully she can point me in the right direction - even if it's just to another specialist - immunologist or whatever. I just think all her issues are too much to leave with a nutritionist.

[ravenwoodglass]

I know, so backwards. Sigh.

She is not autistic, but has many of the co-morbidities, so we were doing biomedical/DAN testing with a nutritionist. IGG testing to different foods is part of the protocal. It was in researching the significance of the IGG results (since it's a controversial test among allergists) that I stumbled across the celiac panel information, and in digging further, started to wonder about celiac (esp. since it is in my family).

Her celiac panel did include AGA IGG and TTG IGG. At least the panel was a good one. But everything was negative - I thought IGG took a lot longer to go down? But yes, everything was negative (with low total IGA).

My nutritionist just called me with more test results (I'll receive them tomorrow in the mail and review them myself, obviously!). It was the CBC and serum cortisol. Her cortisol was low and her CBC showed macrocytic anemia. Initial searching shows that macrocytic anemia can be from B12 or folate deficiency. She had both (and B12 was especially low).

I'm ready for this mystery to be solved! I'm glad an experienced specialist will be reviewing all her labwork, and hopefully she can point me in the right direction - even if it's just to another specialist - immunologist or whatever. I just think all her issues are too much to leave with a nutritionist.

This is strictly my opinion but with the anemia, her test results, her response to the gluten free diet and a family history of celiac I think you already have the answer. I hope the doctor is able to give you a firm answer and that after testing is done you get her on the diet, if the specialist demands a challenge, or keep her on it.

[Skylark]

This is strictly my opinion but with the anemia, her test results, her response to the gluten free diet and a family history of celiac I think you already have the answer. I hope the doctor is able to give you a firm answer and that after testing is done you get her on the diet, if the specialist demands a challenge, or keep her on it.

I have the same opinion. She has so many risk factors and signs of celiac, including DQ2.5. I really hope you find a good doctor and that you don't have to gluten her.

[nora-n]

Here in europe, we usually put children back on gluten for a gluten challenge to get an official diagnosis.

That works normally with DQ2 and DQ8.

But many can have neuro issues from gluten, and antigliadin attacks the brain, etc and does not neccessarily cause the typical gut issues alone. There are more ways gluten can do harm that just in the gut.

If the concept of celiac were to be found now, it would not be a gut issue, but a multisystem syndrome.

You can google ford gluten and read more about the other gluten issues there.

Oh, by thye way, the Enterolab test results mean:

DQ2,5 probably and DQ6

DQ2,5 probably and DQ2,2 (0202)

DQ2,2 and DQ6

0201 is almost always 2,5 because it almost always is together with the 0501 alpha chain just like skylark says.

There are some good charts of the beta and alpha chains at en.wikipedia.org type in HLA DQ

[Gardening]

Thank you all.

I found something on NIH that said it is possible (though rare) to have celiac with just half a gene (or allele or whatever). So my daughter with DQ 2,2 and DQ6 has half a gene in the B sequence 0202. I don't want the doc to say that since she's not 2.5, celiac is impossible, so I will print that out and bring it with me.

I will post an update after the appointment next week.

[nora-n]

If you check out on wikipedia, there are several HLA DQ pages, and 2,2 is definitely a litte bit connected to celiac.

Also, we have had several DQ2,2 posting here with symptoms and questions.