HLA-DQA1*03 gene: does this mean that I can’t totally rule out coeliac?

[BushbabyLou]

Hi everyone,

I'm new here.

I have Hashimoto’s and Sjogren’s and strongly suspect coeliac. I don’t have DQ8 or DQ2 only the alpha subunit for DQ8 (HLA-DQA1*03). As far as I can tell this subunit also codes for DQ3 and DQ7 which are both implicated in coeliac. However, I am not a geneticist so don’t know if I am correct on that one. 

I have recently undertaken the gluten challenge for 6 weeks but my blood test was normal, despite me having the following symptoms; 

Cold hands and feet

Tired all the time

Weight gain

Trouble controlling appetite

Sugar intolerance

Palpitations after gluten and alcohol

Headaches

Aches and pains

Dry, pink eyes 

Dry mouth

Dry skin

Itchiness

Constipation 

Loose stool and diarrhoea 

Painful periods 

Lower back/kidney pain

Lower abdominal pain

Hair thinning

Itchy scalp

Coughing

Sore throat

Runny nose

Smelly Farting

Frequent burping 

Frequent urination

Acid reflux

Itchy ears 

Vomiting 

Nausea 

Hypothyroidism

Burping 

Chest pain 

Easily injured mouth 

Shoulder pain

Hand pain

Heavy legs 

Rash under watch strap

Stiffness and aching in fingers. 

Extremely dry mouth when eating gluten. 

Itchy blistering rash on foot

Slow wound healing 

Puffy face

Plus many more I can’t think of right now
 

I have been told by numerous coeliac sufferers that you can have negative bloods despite eating gluten and that the gold standard for testing is endoscopy. I can totally believe this to be the case as my Sjogren’s bloods were negative but I was positive on biopsy. Also, my Hashimoto’s went under the radar because I had the less common set of antibodies that my dr didn’t test for. 
 

Given my gene test, my symptoms and my existing autoimmune conditions, is it worth me pursuing endoscopy or does the fact that I only have the alpha subunit of DQ8 exclude me from ever having coeliac?

 

Many thanks in advance for the help and sorry for the very long post. 
 

Lucy

 

[trents]

Welcome to the forum, Lou!

Yes, sometimes it does happen that bloods are negative while biopsies are positive and vice versa. But can you be more specific about which serum antibody tests were run and what their values were (along with reference ranges for positive-negative)? Many physicians will order only the tTG-IGA test instead of a "full celiac panel".  https://celiac.org/about-celiac-disease/screening-and-diagnosis/screening/

Some celiacs have immunes responses that are atypical so there is value in running various tests. What is missed by the tTG-IGA test may be picked up by one of the others.

You could also be looking at NCGS (Non Celiac Gluten Sensitivity) for which there is no test, even though they share many of the same symptoms. Celiac disease must first be ruled out. NCGS is 10-12x more common that celiac disease. Having said that, your other autoimmune diseases point to celiac disease. If you are on immunosuppressant meds for these other autoimmune conditions that may explain your negative for celiac testing.

The other option would be to commit to a gluten-free diet/lifestyle and see if symptoms improve. I understand that in some countries there are government subsidies for gluten-free food if you have an official celiac diagnosis but apart from that going totally off gluten should answer your questions except it won't differentiate between celiac disease and NCGS.

The gluten challenge before biopsy is shorter than for the antibody testing. For the biopsy it is only 2 weeks.

 

[knitty kitty]

Welcome to the forum! 

I agree with @trents that the full Celiac panel of blood tests needs to be done while you are consuming gluten. 

Some people are serionegative.  Anemia and diabetes can cause serionegatives.  

So, yes, the endoscopy is worth pursuing.

I'm not a geneticist, but I found some interesting articles about the connection between Celiac Disease and other autoimmune diseases.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678473/

And...

Celiac and Sjogren's

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520766/

And...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971288/

 

[BushbabyLou]

23 minutes ago, trents said:

Welcome to the forum, Lou!

Yes, sometimes it does happen that bloods are negative while biopsies are positive and vice versa. But can you be more specific about which serum antibody tests were run and what their values were (along with reference ranges for positive-negative)? Many physicians will order only the tTG-IGA test instead of a "full celiac panel".  https://celiac.org/about-celiac-disease/screening-and-diagnosis/screening/

Some celiacs have immunes responses that are atypical so there is value in running various tests. What is missed by the tTG-IGA test may be picked up by one of the others.

You could also be looking at NCGS (Non Celiac Gluten Sensitivity) for which there is no test, even though they share many of the same symptoms. Celiac disease must first be ruled out. NCGS is 10-12x more common that celiac disease. Having said that, your other autoimmune diseases point to celiac disease. If you are on immunosuppressant meds for these other autoimmune conditions that may explain your negative for celiac testing.

The other option would be to commit to a gluten-free diet/lifestyle and see if symptoms improve. I understand that in some countries there are government subsidies for gluten-free food if you have an official celiac diagnosis but apart from that going totally off gluten should answer your questions except it won't differentiate between celiac disease and NCGS.

The gluten challenge before biopsy is shorter than for the antibody testing. For the biopsy it is only 2 weeks.

 

Hi Trents, 

thank you so much for your reply! I had the following bloods with the following reference range;

TTg 0.2 (range 0-10)

IgA 0.99 (range 0.8-2.8)

I’m on two immunomodulators; Low Dose Naltrexone and Hydroxychloroquine. Not sure if they could prevent me showing the antibodies. 
 

Do you think it matters that I only have the alpha subunit if dq8 and not the heterodimer? 
 

My symptoms definitely clear up when I’m gluten free. I’ve been gluten free most of my adult life but do let gluten creep back in. Normally my symptoms clear up quickly after eating gluten but this time after the six weeks it’s taking a lot longer. 
 

That’s so good to know that the gluten challenge is so much shorter for the biopsy. 

15 minutes ago, knitty kitty said:

Welcome to the forum! 

I agree with @trents that the full Celiac panel of blood tests needs to be done while you are consuming gluten. 

Some people are serionegative.  Anemia and diabetes can cause serionegatives.  

So, yes, the endoscopy is worth pursuing.

I'm not a geneticist, but I found some interesting articles about the connection between Celiac Disease and other autoimmune diseases.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678473/

And...

Celiac and Sjogren's

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520766/

And...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971288/

 

Hi Knitty Kitty,

 

thank you so much for your reply and for looking up the articles for me. I will give them a read. 
 

My blood test results were;

TTG 0.2 (range 0-10)

IgA 0.99 (range 0.8-2.8)

 

 

[knitty kitty]

Be careful taking Hydroxychloroquine.  It can cause thiamine deficiency.  Are your doctors keeping tabs on your thiamine level???

Drug–nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR-2 (SLC19A3)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944527/

Some of the symptoms you listed are also symptoms of thiamine deficiency.  

[Wheatwacked]

Have you had tests for blood level of Vitamin D. Urine Iodine Test? Homocysteine? vitamin D at the appropriate plasma level moderates the autoimmune response. Iodine deficiency is a cause of hypothyroid and will help muscle tone that will help the pains and can cause slow healing. To process the homocysteine in the blood we need sufficient B6, B12, folate and choline working together.

Hypothyroidism typically causes symptoms that can include:

Vitamin D and the Immune System

You at least have Gluten Sensitivity, either Celiac or Non-Celiac Gluten Sensitivity by your response to the Gluten Challenge. I had 18 symptoms that cleared from GFD alone and more that were deficiencies.  I needed 30 mg of prednisone for the aches and pains. Two years later I started GFD I only need 5 or 10 a day. I only need it now because the prednisone caused Secondary Adrenal Insufficiency. A shame it wasn't GFD first. 

Hydroxychloroquine may cause side effects. 

"Based on these, it will be interesting to investigate whether thiamine deficiency might underlie some of the CQ-induced adverse effects and whether these can be prevented with concomitant thiamine supplementation. "In this study, we demonstrated that CQ and other quinoline-containing antimalarials inhibit thiamine transporters in yeast. We also showed that such a MOA is conserved between yeast and humans. In particular, the human thiamine transporter SLC19A3 was completely inhibited by CQ when expressed in yeast cells Discovering Thiamine Transporters as Targets of Chloroquine

 

[T burd]

From what I understand the genetic test is only about 95% accurate. It only tests the most common genes related to celiac. They also don’t really know all the obscure genes for celiac at this time.

I think your labs should have one number for ttg iga ? 

there are other labs that should be done for a full panel. my sister went to an older gastroenterologist and he only tested

TTG-IGA

it was negative. He didn’t do a full panel on her.

she went to a family physician who did a full panel and she had ttg igg positive. 
 

if you do the biopsy make sure they do a separate biopsy for your duodenal bulb. that is not standard in the US. One study the Mayo Clinic publish shows that only about one percent of people with celiac have the bulb positive where the duodenal biopsy is negative. 
 

 my duodenal bulb was positive where my duodenal biopsy was negative. When my sister got her biopsy they did not do a separate biopsy on her duodenal bulb. And her test was negative. So she was not able to get a diagnosis.

I know the duodenal biopsy is the gold standard but I also heard from other people who said that their father had biopsies seven times before one was positive. Sometimes the damage is hidden and just in a certain section that they don’t test in the biopsy. 
I also have other autoimmune issues that make me feel worse than Celiac because I didn’t get my diagnosis of celiac until I was 38. I started feeling bad after my 3rd child at 34. 

I have high ANA. and a histone positive, meaning it’s drug induced lupus…. that was diagnosed at 40. DIL is supposed to go away and mine hasn’t seemed to.
I was on hydroxychloroquine for 10 months and my heart started having palpitations so I stopped taking it but ever since then it’s been getting worse. my heart has been getting worse and my joint pains and crepitus. I stopped it 10 months ago. 
 

that other response saying that hydroxychloroquine can cause other deficiencies is helpful to me.

I just started going to a functional medicine doctor and she ordered a bunch of labs that no other doctors have ordered before. 

she suspects I probably contracted lyme as a child having many ticks that I can’t even count. 

If you have one autoimmune issue it causes others. 
 

 

[knitty kitty]

 

@T burd, welcome to the forum!

Do look into thiamine deficiency.

Here's an interesting article for you...

Wernicke's encephalopathy mimicking neuropsychiatric symptoms in patients with systemic lupus erythematosus: a report of three cases and literature review

https://pubmed.ncbi.nlm.nih.gov/27416844/

[Wheatwacked]

For years I suspected Lymes disease because my dog tested positive for it in 1986 and of my fibromyalgia like symptoms but was always blown off by the doctors. My current doctor ordered the test, after 32 years of asking. I do not have Lyme. Once I knew it was not, I could focus on malnutrition.

[T burd]

1 hour ago, Wheatwacked said:

For years I suspected Lymes disease because my dog tested positive for it in 1986 and of my fibromyalgia like symptoms but was always blown off by the doctors. My current doctor ordered the test, after 32 years of asking. I do not have Lyme. Once I knew it was not, I could focus on malnutrition.

After 30 years the antibody blood test would not always show Lyme even if you did have it. Lyme hides in joints and bones. 
I know a girl who is 17 who had Lyme as a 6 year old child and her pill addict mother didn’t put her on the full antibiotic regimen. She is starting to have joint pains now but her blood tests are negative.