Are You A Biopsy Confirmed Celiac But Gene Negative?

[researchmomma]

I am frustrated by the pat answer: if you don't have the DQ2 or DQ8 genes you do NOT have Celiac. In Europe, they recognize several other HLA DQ genes as Celiac genes. In addition, there has been research to suggest that even if you don't have any of the HLA genes, you can still have Celiac.

The GI we go to insists that all Celiac patients have either DQ2 or DQ8 (100% confidence). I know this isn't true since I have conversed with at least one person on this site that is not DQ2 or DQ8 and had a positive biopsy for Celiac Disease.

So I would like to be able to tell her how many people on this site are confirmed Celiac by biopsy and gene negative for DQ2 or 8. I realize that I just want to prove her wrong but I can't help myself because some sick person with Celiac could walk out of her office undiagnosed and eating gluten! Or maybe I am crazy. Feel free to let me know!

All comments welcome.

[ravenwoodglass]

Although the second challenge my GI insisted on resulted in a severe GI bleed so I was unable to have the biopsy my DD did have one and much later had her genes tested. Our GI diagnosed her based on positive blood work and biopsy but later when had had gone to college she had her genes tested and her new GI told her she couldn't be celiac because she didn't have the genes for it. I am a double DQ9 so she has to have at least one copy of that gene but I don't know the results of her other gene.

I am a firmly diagnosed celiac who didn't show up in the older tests and I don't carry either of the most common celiac associated genes. IMHO the gene tests should not be considered diagnostic one way or the other. There are celiacs without those genes and there are folks who do have the genes and never develop celiac.

I answered the poll with her results as I didn't have an endo until after I was well healed 5 years after diagnosis.

[sa1937]

I'd be curious to know how many people are blood and biopsy diagnosed who have no clue what their genes are. I'd be one of them.

[catsmeow]

I do not not have Celiac's, I have a wheat allergy and am gluten sensitive. I did have a Celiac blood test, but it was negative, by the time my doc tested me, I had been gluten-free for a year. I did Gene testing and it showed that I do not have Celiac genes, I have gluten sensitive genes.

My results:

Gluten Sensitivity Gene Test

HLA-DQB1 Molecular analysis, Allele 1 0501

HLA-DQB1 Molecular analysis, Allele 2 0402

Serologic equivalent: HLA-DQ 1,4 (Subtype 5,4)

Interpretation Of HLA-DQ Testing: Although you do not possess one of the main HLA-DQB1 genes predisposing to celiac sprue (HLA-DQB1*0201 or HLA-DQB1*0302), HLA gene analysis reveals that you have one copy of a gene that predisposes to gluten sensitivity (any DQ1, DQ2 not by HLA-DQB1*0201, or DQ3 not by HLA-DQB1*0302). Having one of these genes means that each of your offspring has a 50% chance of receiving this gene from you, and at least one of your parents passed it to you. This test was developed and its performance characteristics determined by the American Red Cross - Northeast Division. It has not been cleared or approved by the U.S. Food and Drug Administration.

[IrishHeart]

My GI doc told me he biopsied a man who had neither of these genes and his villi were totally flat. He said "so much for the 'celiac genes"."

[catsmeow]

  On 12/17/2011 at 3:47 AM, IrishHeart said:

My GI doc told me he biopsied a man who had neither of these genes and his villi were totally flat. He said "so much for the 'celiac genes"."

Yep...it makes me wonder sometimes..........

[researchmomma]

Thank you for answering. I hope more do.

I had dinner last night with a good friend who is a Dermatologist. I shared my story with her and she said I completely believe there are people out there that are DQ2 or 8 negative with Celiac.

She has had 3 patients quite recently that had DH and she sent them to a GI. The GIs did blood work and GI testing and because the gene test was negative they were told that they weren't Celiac. The patients came back to her and she was shocked at the stupidity. She told these patients to go gluten free and she does not refer to THAT GI anymore.

[IrishHeart]

  On 12/17/2011 at 3:13 PM, researchmomma said:

Thank you for answering. I hope more do.

I had dinner last night with a good friend who is a Dermatologist. I shared my story with her and she said I completely believe there are people out there that are DQ2 or 8 negative with Celiac.

She has had 3 patients quite recently that had DH and she sent them to a GI. The GIs did blood work and GI testing and because the gene test was negative they were told that they weren't Celiac. The patients came back to her and she was shocked at the stupidity. She told these patients to go gluten free and she does not refer to THAT GI anymore.

This DERM needs to send this GI some CURRENT medical info that states plainly that DH IS the skin manifestation of CELIAC!!!!!! For theloveofmike....

She can DX them with biopsy of the lesions.

[maramelia]

  On 12/17/2011 at 3:13 PM, researchmomma said:

Thank you for answering. I hope more do.

I had dinner last night with a good friend who is a Dermatologist. I shared my story with her and she said I completely believe there are people out there that are DQ2 or 8 negative with Celiac.

She has had 3 patients quite recently that had DH and she sent them to a GI. The GIs did blood work and GI testing and because the gene test was negative they were told that they weren't Celiac. The patients came back to her and she was shocked at the stupidity. She told these patients to go gluten free and she does not refer to THAT GI anymore.

researchmomma, i loved your poll!!!

for our knowledge: my boy started this year to decline on growth, achieved 2.5% of growth chart curve >> short stature >>> began investigation >> ferroprive anemia + hypothyroidism + short stature + inconclusive GH deficiency blood exams >> TTG mild positive >>> EMA negative >> Marsh I positive biopsy >>> started GFD in Nov 18/2011 >> did HLA gene tests concomitantly === NEGATIVE!!!!

Our gastroped >>> maintain gluten free diet >>> lets wait >>> today, after 5 weeks of no gluten >>> HUGE IMPROVEMENT OF GI SYMPTOMS (eating better, no distentions, no more mild abdominal pain)...

Last saturday, after nutritionist consultation >>> he is 1cm taller than 1 month ago!!!!!! coincidence?!

Im sure >>> If this os not celiac disease, it is some sort of gluten sensivity / intolerance / allergy / what whatever any expetise physician want to call this >>> and it is working!!!! my son is catching up growth, thanks to God, My Mother N. S. Aparecida (Gods Mother), and thanks to our pediatrician Dr. Marta, who was the one who send him to do the TTG blood exam, when everything started to suspect of celiac disease...

SO, i DO BELIEVE IN WHAT YOU THINK: although I'm a physician (actually, I'm a neurologist!!!), working in academic practice here in Brazil, and i really believe in research, clinical and med papers, clinical studies, large clinical trials, epidemiological studies, etc... I know there are some studies with the story of 98% of HLA positive exams in celiac disease...

I think there are more things than what we doctors know today about celiac disease... And this story of only 0,4% of celiac disease patients being negative-HLA DQ2 and DQ8... hummm... this is strange : there is no 100% negative predictive value or 100% positive predictive value blood exam... i don't believe in this...

If you want, i can send you an article written by Alessio Catassi, about this field...

Regards, Mara

[maramelia]

  On 12/20/2011 at 12:06 AM, maramelia said:

researchmomma, i loved your poll!!!

for our knowledge: my boy started this year to decline on growth, achieved 2.5% of growth chart curve >> short stature >>> began investigation >> ferroprive anemia + hypothyroidism + short stature + inconclusive GH deficiency blood exams >> TTG mild positive >>> EMA negative >> Marsh I positive biopsy >>> started GFD in Nov 18/2011 >> did HLA gene tests concomitantly === NEGATIVE!!!!

Our gastroped >>> maintain gluten free diet >>> lets wait >>> today, after 5 weeks of no gluten >>> HUGE IMPROVEMENT OF GI SYMPTOMS (eating better, no distentions, no more mild abdominal pain)...

Last saturday, after nutritionist consultation >>> he is 1cm taller than 1 month ago!!!!!! coincidence?!

Im sure >>> If this os not celiac disease, it is some sort of gluten sensivity / intolerance / allergy / what whatever any expetise physician want to call this >>> and it is working!!!! my son is catching up growth, thanks to God, My Mother N. S. Aparecida (Gods Mother), and thanks to our pediatrician Dr. Marta, who was the one who send him to do the TTG blood exam, when everything started to suspect of celiac disease...

SO, i DO BELIEVE IN WHAT YOU THINK: although I'm a physician (actually, I'm a neurologist!!!), working in academic practice here in Brazil, and i really believe in research, clinical and med papers, clinical studies, large clinical trials, epidemiological studies, etc... I know there are some studies with the story of 98% of HLA positive exams in celiac disease...

I think there are more things than what we doctors know today about celiac disease... And this story of only 0,4% of celiac disease patients being negative-HLA DQ2 and DQ8... hummm... this is strange : there is no 100% negative predictive value or 100% positive predictive value blood exam... i don't believe in this...

If you want, i can send you an article written by Alessio Catassi, about this field...

Regards, Mara

by the way, I'm one who answered your poll / research!!! my pacient (my boy) is a negative HLA and positive Biopsy... i don't know if he is celiac, but he is doing very good on GFD. We know biopsy results are not so specific for celiac disease, they may show just an inflammatory enteropathy... but... whatever!!!!

[love2travel]

  On 12/17/2011 at 2:49 AM, sa1937 said:

I'd be curious to know how many people are blood and biopsy diagnosed who have no clue what their genes are. I'd be one of them.

As am I. I have no idea.

[IrishHeart]

Genetic testing can be done through your physician or by independent labs.

Saliva, blood or stool sample.

I did mine by saliva swab, but my GI wanted to confirm via stool testing.

Results were the same. (For those who doubt Enterolab's saliva gene test)

[Bubba's Mom]

I had negative blood tests, but positive endoscope. I wasn't given the gene test.

I just went to a new GI because my health hasn't been improving. He ordered the gene test. He told me it can tell if I DON'T have Celiac..but can't definitely say I do.

I'm wondering if he is one who thinks you MUST have DQ2 or DQ8?

I've read that there are other genes that show gluten problems.

It will be interesting to see what my results will be.

[IrishHeart]

  On 12/20/2011 at 3:10 PM, Bubba said:

I had negative blood tests, but positive endoscope. I wasn't given the gene test.

I just went to a new GI because my health hasn't been improving. He ordered the gene test. He told me it can tell if I DON'T have Celiac..but can't definitely say I do.

I'm wondering if he is one who thinks you MUST have DQ2 or DQ8?

I've read that there are other genes that show gluten problems.

It will be interesting to see what my results will be.

I do not understand. You had a positive biopsy & you have celiac, so why would he bother?????? A genetic test was primarily used as a means of exclusion.

Does he think the villi were damaged by some other means?

[Skylark]

Your question has already been answered with a 10,000 person genetic study. There are a few biopsy-confirmed celiacs without the genes. The risk of having celiac disease without DQ2 or DQ8 in the study was 0.16%, meaning it's unusual but absolutely not impossible.

Open Original Shared Link

[Roda]

  On 12/17/2011 at 2:49 AM, sa1937 said:

I'd be curious to know how many people are blood and biopsy diagnosed who have no clue what their genes are. I'd be one of them.

Me too! Blood and biopsy diagnosed. I've never had the gene testing done. I am considering it for my youngest son. If he was to have the two "common" genes I could get an official diagnosis for him since we didn't put him through a biopsy. Then again I know he has celiac and I may just leave it at that!

[Bubba's Mom]

  On 12/20/2011 at 3:15 PM, IrishHeart said:

I do not understand. You had a positive biopsy & you have celiac, so why would he bother?????? A genetic test was primarily used as a means of exclusion.

Does he think the villi were damaged by some other means?

My PCP doesn't believe the DX I got because I had negative blood work. I also have been having ongoing nausea, insomnia, and weight loss. When I asked her to run a blood panel to see if I was low on some vitamin or mineral she asked if I take a multi-vitamin and I said yes. She told me that I couldn't be lacking anything then and refused the test. She treats me like a hypochondriac.

My biopsy report also mentioned a couple other things that could be looked into. I went to a new GI to see if he could figure out why I'm not feeling better. He said I should have the genetic test.

[frieze]

  On 12/20/2011 at 5:31 PM, Skylark said:

Your question has already been answered with a 10,000 person genetic study. There are a few biopsy-confirmed celiacs without the genes. The risk of having celiac disease without DQ2 or DQ8 in the study was 0.16%, meaning it's unusual but absolutely not impossible.

Open Original Shared Link

but what about persons that were refused the biopsy because they were gene negative?

[researchmomma]

  On 12/20/2011 at 12:06 AM, maramelia said:

researchmomma, i loved your poll!!!

for our knowledge: my boy started this year to decline on growth, achieved 2.5% of growth chart curve >> short stature >>> began investigation >> ferroprive anemia + hypothyroidism + short stature + inconclusive GH deficiency blood exams >> TTG mild positive >>> EMA negative >> Marsh I positive biopsy >>> started GFD in Nov 18/2011 >> did HLA gene tests concomitantly === NEGATIVE!!!!

Our gastroped >>> maintain gluten free diet >>> lets wait >>> today, after 5 weeks of no gluten >>> HUGE IMPROVEMENT OF GI SYMPTOMS (eating better, no distentions, no more mild abdominal pain)...

Last saturday, after nutritionist consultation >>> he is 1cm taller than 1 month ago!!!!!! coincidence?!

Im sure >>> If this os not celiac disease, it is some sort of gluten sensivity / intolerance / allergy / what whatever any expetise physician want to call this >>> and it is working!!!! my son is catching up growth, thanks to God, My Mother N. S. Aparecida (Gods Mother), and thanks to our pediatrician Dr. Marta, who was the one who send him to do the TTG blood exam, when everything started to suspect of celiac disease...

SO, i DO BELIEVE IN WHAT YOU THINK: although I'm a physician (actually, I'm a neurologist!!!), working in academic practice here in Brazil, and i really believe in research, clinical and med papers, clinical studies, large clinical trials, epidemiological studies, etc... I know there are some studies with the story of 98% of HLA positive exams in celiac disease...

I think there are more things than what we doctors know today about celiac disease... And this story of only 0,4% of celiac disease patients being negative-HLA DQ2 and DQ8... hummm... this is strange : there is no 100% negative predictive value or 100% positive predictive value blood exam... i don't believe in this...

If you want, i can send you an article written by Alessio Catassi, about this field...

Regards, Mara

Mara, I would love the article. I am sorry it took me so long to respond. At a friend's advice I skipped the word gluten free yesterday because it has been all consuming. It was such a nice mental break!!! But I am BACK.

Here is what I learned from a researcher that is doing non-HLA studies at University California Irvine: 5% of confirmed Celiacs are gene negative (registry of 1015 celiacs from all over the world, I will confirm that number with her)! She doesn't understand why our GI won't biopsy my daughter. BUT it doesn't matter. We are gluten free now and we will see how we do.

Someone said "So what is this nonsense about going gluten free". How RUDE. And I promised by daughter that I was gluten-free with her. I SWORE it to her and this friend said eat the pizza I brought she won't know. UGH. I am doing this so I know how difficult her challenges are when she goes to someones house for dinner or goes out to eat. She needs my support at 12 years old.

Sorry for venting. It was a rough day and she had a sore stomach last night after 10 days of gluten-free and doing pretty well. So my hubs is now thinking it isn't gluten. Luckily someone on here had posted about up and down days in early states of going gluten-free.

Rant over. Thanks!

[researchmomma]

  On 12/17/2011 at 3:47 AM, IrishHeart said:

My GI doc told me he biopsied a man who had neither of these genes and his villi were totally flat. He said "so much for the 'celiac genes"."

Wow, what an open minded individual.

[researchmomma]

  On 12/21/2011 at 5:53 PM, frieze said:

but what about persons that were refused the biopsy because they were gene negative?

Like my daughter.

AND as I said before there is a large registry study at UCI and they said 5% of the individuals with biopsy confirmed celiac did not have the HLA DQ 2 or 8 genes. She said that is "a lot" of people and your GI should know that.

[Skylark]

  On 12/21/2011 at 5:53 PM, frieze said:

but what about persons that were refused the biopsy because they were gene negative?

Did you even bother to read the abstract???

As the abstract states, they were looking at anti-EMA IgA as the measure of celiac and tested genes and antibodies at the same time in a single blood draw. Anti-EMA has about a 25% false negative rate but it's very specific. There will be a bit of underestimation of celiac rates across the study, but the relative risk across genotypes is not affected.

[Skylark]

  On 12/21/2011 at 9:48 PM, researchmomma said:

Someone said "So what is this nonsense about going gluten free". How RUDE. And I promised by daughter that I was gluten-free with her. I SWORE it to her and this friend said eat the pizza I brought she won't know. UGH. I am doing this so I know how difficult her challenges are when she goes to someones house for dinner or goes out to eat. She needs my support at 12 years old.

You might be the best mom ever. I'm deeply impressed that you are struggling through the diet to support your daughter.

[researchmomma]

  On 12/21/2011 at 10:14 PM, Skylark said:

You might be the best mom ever. I'm deeply impressed that you are struggling through the diet to support your daughter.

What a nice comment. I have had a rough week so this was nice to hear. I bet there are loads and loads of moms that do this.

[maramelia]

  On 12/21/2011 at 10:11 PM, Skylark said:

Did you even bother to read the abstract???

As the abstract states, they were looking at anti-EMA IgA as the measure of celiac and tested genes and antibodies at the same time in a single blood draw. Anti-EMA has about a 25% false negative rate but it's very specific. There will be a bit of underestimation of celiac rates across the study, but the relative risk across genotypes is not affected.

i read the abstact, didnt read the hole article, but i have some considerations:

- methodology = in the 10,000 pts article, did they use the EMA as the celiac disease confirmation? in my opinion, this is not a good accuracy method to compare the HLA tests...

- in my opinion, the best would be to compare people with a kind of multiple dignostic criteria, just like, for example, response to GFD+ positive biopsy + some sort of aditional symptoms, just like ferroprive anemia / autoimune symptom / DH or hypothoroidism or classical symptoms... === and in those with no doubt of celiac disease >>> to do the gene tests...

- to do a study to screen people, this makes the methodology works to the tests...

rgds mara