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DQ8 Causes More Than Just Celiac Disease

Celiac.com 08/18/2009 - Many of you know that DQ8 is one of the two major genes which may lead to celiac disease. You may also know that celiac disease is often associated with various other autoimmune diseases. What you may not know is that DQ8 may be the direct cause of these other autoimmune diseases, for these autoimmune diseases are found in increased incidence not just in celiac disease, but also with DQ8 itself.

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What follows is a list I have compiled showing the various diseases that are found in increased frequency among people who have the DQ8 gene (DQB1*0302). I will show the reference number next to each, and the corresponding references will appear below:

  • Celiac disease (1)
  • Scleroderma (2)
  • Rheumatoid arthritis (1)
  • Autoimmune thyroiditis (3)
  • Pemphigus (4)
  • Lupus (6)
  • Pemphigoid (5)
  • Focal myositis (7)
  • Multiple sclerosis (8)
  • Myasthenia gravis (1)
  • Insulin dependant latent autoimmune diabetes of adults and adult Type 1 diabetes (9)
  • Type 1 juvenile diabetes (1)
  • Sjogren’s syndrome (10)
  • Addisons’s disease (11)
  • Complex regional pain syndrome with dystonia (12)
  • Latex allergy (13)
This list is not intended to be exhaustive. It is a starter list. Hopefully more research will be done on these, including carefully controlled research as to whether gluten plays any role in triggering these other autoimmune diseases even in the absence of gluten blood antibodies or positive duodenal biopsies. I, for one have DQ8 and numerous of these autoimmune diseases, even though my gluten blood antibodies and duodenal biopsies are negative. We who have this gene need to know for certain #1 whether a gluten free diet will help prevent the triggering of these other various autoimmune diseases, and #2 whether a gluten-free diet will help mitigate autoimmune symptoms that have already developed. I feel no better on the gluten-free diet than before I started it a year and a half ago. However, if I had not been on the diet, perhaps I would be feeling even worse now. Only controlled research will give us the answer.

References:

  1. http://en.wikipedia.org/wiki/HLA-DQ8
  2. Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis. Frank C. Arnett, MD, John D. Reveille, MDet al. See abstract at http://www3.interscience.wiley.com/journal/112212324/abstract.
  3. A strong association between thyrotropin receptor-blocking antibody- positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1*0302 in Koreans. Cho, JH Chung, YK Shong, YB Chang, H Han, JB Lee, HK Lee and CS Koh. See abstract at http://jcem.endojournals.org/cgi/content/abstract/77/3/611.
  4. Association between HLA-DRB1, DQB1 genes and pemphigus vulgaris in Chinese HansBy Zhou SH, Lin L, Jin PY, Ye SZ. See abstract at: http://www.ncbi.nlm.nih.gov/pubmed/12579512.
  5. Polymorphisms of HLA-DR and -DQ Genes in Japanese Patients with Bullous Pemphigoid. By Okazaki A, Miyagawa S, et al. See abstract at: http://sciencelinks.jp/j-east/article/200017/000020001700A0339663.php.
  6. HLA-DRB1*03 and DQB1*0302 associations in a subset of patients severely affected with systemic lupus erythematosus from western India. By U Shankarkumar, K Ghosh, S S Badakere, D Mohanty. See abstract at: http://ard.bmj.com/cgi/content/extract/62/1/92.
  7. HLA typing in focal myositis. By Kenji Sekiguchi, Fumio Kanda, Kenichi Oishi, Hirotoshi Hamaguchi, Kenichiro Nakazawa, Nobuya Maeda, Hiroyuki Ishihara and Kazuo Chihara. See abstract at: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T06-4DB5B4F-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=975695599&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=36883393fca9b990607eeb0d38116c5a.
  8. HLA-DRB1*1501, -DQB1*0301, -DQB1*0302, -DQB1*0602, and -DQB1*0603 alleles are associated with more severe disease outcome on MRI in patients with multiple sclerosis. By Zivadinov Robert; Uxa Laura et al. See abstract at: http://www.biomedexperts.com/Abstract.bme/17531857/HLA-DRB1_1501_-DQB1_0301_-DQB1_0302_-DQB1_0602_and_-DQB1_0603_alleles_are_associated_with_more_severe_disease_outcome.
  9. Similar Genetic Features and Different Islet Cell Autoantibody Pattern of Latent Autoimmune Diabetes in Adults (LADA) Compared With Adult-Onset Type 1 Diabetes With Rapid ProgressionBy Nóra Hosszúfalusi, MD, PHD, Ágnes Vatay, MD1, et al. See abstract at http://care.diabetesjournals.org/content/26/2/452.full.
  10. Specific amino acid residues in the second hypervariable region of HLA- DQA1 and DQB1 chain genes promote the Ro (SS-A)/La (SS-B) autoantibody responses. ByJD Reveille, MJ Macleod, K Whittington and FC Arnett. See abstract at http://www.jimmunol.org/cgi/content/abstract/146/11/3871.
  11. Analysis of extended human leukocyte antigen haplotype association with Addison’s disease in three populations. ByGombos, Hermann, et al. See study at: http://www.eje-online.org/cgi/reprint/157/6/757.pdf.
  12. HLA-B62 and HLA-DQ8 are associated with Complex Regional Pain Syndrome with fixed dystonia. By Rooij, Gosso, et al. See study at: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0K-4WH0JWP-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=c869b6d3a38081820fad17c162b510ba.
  13. HLA-DQ8 and the HLA-DQ8-DR4 haplotype are positively associated with the hevein-specific IgE immune response in health care workers with latex allergy. By  Rihs Hans-Peter; Chen Zhiping; Ruëff Franziska; et al. See abstract at: http://www.biomedexperts.com/Abstract.bme/12209103/HLA-DQ8_and_the_HLA-DQ8-DR4_haplotype_are_positively_associated_with_the_hevein-specific_IgE_immune_response_in_health_c

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6 Responses:

 
Anne
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said this on
22 Aug 2009 5:32:40 AM PDT
You say that you are feeling no better on a gluten-free diet. Many of us have found that in order to feel well we need to eliminate more than gluten. I discovered I react strongly to yeast. In fact, when I first went gluten-free I though all yeast breads were contaminated with wheat because of the reaction I had. I have also discovered that I feel best when I eat no grains and no dairy. Have you looked into the possibility that you may be reacting to other foods?

Thanks you for this article and references.

 
Amanda
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said this on
03 Sep 2009 4:16:32 PM PDT
I too had the negative results on my blood work, but my attacks stopped once I went on the gluten free diet. About a year into the diet I found that I also had issues with Xanthan gum. Now two years in, I have begun to struggle with hypoglycemia attacks and extreme fatigue. I was recently put on a structured diet including protein supplements. The attacks have stopped but the fatigue is becoming worse. I've been to several doctors that all say my lab work checks out, but have no suggestions or answers to why I feel so poorly. So, if the new diet doesn't work they are sending me off for more tests. So, I think that celiac can just be the tip of the iceberg. Any suggestions or insight is welcome.

 
Celiac
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said this on
21 Oct 2010 11:57:36 AM PDT
My personal opinion is that if you don't feel any better/get worse/no clinical lab or test results improve on the gluten free diet than gluten is not your problem. I hear of so many "gluten intolerant" people who think they have some form of celiac say "but I didn't start to feel better until I cut out dairy/yeast/fruit, etc. Well, then maybe that was what the problem was...what indicates it would be gluten then? It just doesn't make any sense. Just having the genes for celiac or some symptoms of celiac doesn't mean you have celiac or NCGI. And if you still are getting sick, it's entirely possible that food plays little to no role in your illness to begin with unless allergy or intolerance testing proves otherwise. Do I think that a subset of people with autoimmunity/genes/family history for autoimmunity will improve or be helped by being gluten free? Yes. Definitely. I bet some of those people definitely should most certainly be gluten free. However, I suspect that a lot of people are thinking gluten is the problem when really it's not. I mean, if you don't actually have celiac, and if you don't improve or you continue to be ill, what is the point of being gluten free? Likely there is something else going on that requires testing, not cutting out more foods. Although there are people out there who truly have an immune (IgE, IgA, IgM, etc.) reaction to multiple and many (if not all) foods. But they need to be under the care of a specialist anyway. I know because I am one of those people. I also think people in general eat a lot of junk and processed foods, which have additives that bother some people. It's not necessarily gluten that people are reacting to. I do agree 100% with the author that more research does need to be done.

 
Lisa Cairncross
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said this on
27 Feb 2012 8:08:14 AM PDT
Having gone undiagnosed or misdiagnosed for 42 years, I'll never know when my Celiac Disease became active. Once dx'd I removed all gluten from my diet and did indeed get worse and was subsequently diagnosed with Fibromyalgia. The endoscopy performed at one year gluten free revealed increased damage/blunting of my villi. I continued to get sicker and sicker until I had maybe an hour of vertical time per day (right when I awoke and there was no food in my body).

I was gluten free two and a half years before I eliminated all possible food intolerances at once to trial them each separately over a six month period. Within three days of eliminating Grains, Nightshades, Legumes, Nuts, Dairy and Citrus I was up out of bed (had been bedridden for over a year) and have continued to slowly improve with the exception of some horrible days during food trial.

I now believe that a lifetime of gluten destroyed my digestive system which led to other food intolerances. Now that I have removed these foods I have new hope that my digestive system will have an opportunity to heal and I will gain some foods back, but never Gluten. If I am incorrect and never get these foods back -- at least I am out of bed, feeling great (most days) and have a life once again.

PS All three of my children and two grandchildren had negative celiac panels, but have all had greatly improved health on a gluten free diet. Two children had to remove a few other foods through elimination...and are also now healthier than ever before. I am certain they were on the same path as me and would have only got sicker as the decades passed.

 
Dee Hayes
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said this on
21 Feb 2015 11:01:07 AM PDT
I would like a list of the foods you eat because I have been eliminating the same foods over the past decade and am feeling frustrated and hunger about what to eat. Thanks.

 
Urooj
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said this on
29 Nov 2013 7:03:44 AM PDT
This probably explains why having one autoimmune disease increases your risk for others. They're all closely related (genetic profile wise). I am Pakistani, positive for the HLA-DQ8 gene. Celiac disease is fairly prominent in South Asia too, and I think it's the only gene that is related to Celiac there (HLA-DQ2 is fairly absent).




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Hello I was diagnosed Dec 15 of last year and went totally gluten-free the next day. I actually got worse before I got better - it's a steep learning curve - but now, 4 1/2 months later I'm finally seeing improvement. Hang in there.

Called my GI doctor today to make sure he is going to look at my small intestine and do biopsy for Celiac for my EGD and he is. Thanks for the tip everyone about have to start eating gluten again. The office told me to break my gluten free diet and start eating gluten everyday until my EGD. Here's to being miserable again for a few weeks ???

I can completely relate! The horrible mental effects that I have been living with for years is the absolute worst side effect of eating gluten, HANDS DOWN. Worse than the endless tummy aches, worse than the constant diarrhea, worse than the week long migraines, worse than the daily fatigue and body pain.... I honestly though there was something seriously wrong with me and hated my life because of how I felt mentally. I always felt like I was drowning, not in control of my thoughts, trapped in some unexplained misery. My head was always so cloudy, and I was mad because I always felt so slow and stupid. I would feel so lethargic and sad and empty while at the same time be raging inside, wanting to rip out of my own skin. I was mean, terrible, would snap at the people closest to me for no good reason and just felt like I hated everyone and everything. Think of how crappy you feel when you have a terrible cold and flu - I felt that crappy, but mentally. Some days were really bad, some were mild. I always thought it was because I was getting a migraine, or because I had a migraine, or because I had just overcome a migraine, because I didn't sleep well, because....always a random reason to justify why we have all these weird unrelated symptoms before we get diagnosed. I'm happy to say that I have been gluten-free for about 2 months now and though I am not symptom free, the first thing that improved was my mood. I no longer feel foggy and miserable. For the first time in years, my head is clear, I can actually think, and I feel positive and like I am in control of what's going on in my head. I don't hate the world. I don't spend every day bawled up on the corner of the couch depressed and angry. The release of these horrible symptoms is enough to never make me want to cheat, no matter what I have to miss out on. So insane how a little minuscule amount of a stupid protein can wreck such havoc.

I wanted to collect some of the info on NCGI in one place so that visitors who test negative but may still have an issue with gluten can be directed there. I'll add to this post as I find new links, but feel free to add or contribute anything you think may be of use! Matt --- Useful links: An overview from Alessio Fasano, one of the world's leading researchers on celiac and gluten sensitivity: https://www.youtube.com/watch?v=VvfTV57iPUY Umberto Volta, another leading researcher in the field gives some of the latest findings about NCGI: Presentation slides from Dr Volta's visit to Coeliac UK - NCGS about halfway through A scholarly overview from celiac disease magazine: https://www.researchgate.net/profile/Knut_Lundin/publication/232528784_Non-celiac_Gluten_Sensitivity/links/09e415098bbe37c05b000000.pdf A good overview from a sceptical but fair perspective: https://sciencebasedmedicine.org/a-balanced-look-at-gluten-sensitivity/ Another overview: https://celiac.org/celiac-disease/understanding-celiac-disease-2/non-celiac-gluten-sensitivity-2/ University of Chicago's excellent celiac site's take: http://www.cureceliacdisease.org/category/faq-non-celiac-gluten-sensitivity/ A compelling account in the British Medical Journal from an NCGI patient: http://www.bmj.com/content/345/bmj.e7982 Here's some positive news about a potential new test: http://www.medicaldaily.com/non-celiac-gluten-insensitivity-blood-test-392850 NCGI in children: NCGI and auto immune study: https://www.ncbi.nlm.nih.gov/pubmed/26026392 Also consider: Fodmaps: http://www.kcl.ac.uk/lsm/research/divisions/dns/projects/fodmaps/faq.aspx This Monash study: http://fodmapmonash.blogspot.co.uk/2015/03/the-truth-behind-non-celiac-gluten.html suggested some who think they're reacting to gluten should actually be reducing fodmaps Sibo: http://www.webmd.boots.com/digestive-disorders/small-intestinal-bacteria-sibo

I was just diagnosed in March and I totally feel you. I'm having a hard enough time with determining which lip glosses are safe, let alone all my face products etc. I feel like this 'grey area' is the biggest annoyance with Celiac. So many foods/cosmetics I thought were safe after reading the ingredient list are actually not safe at all! One website says it's safe, one says its not. All these unfamiliar ingredients and even after googling term after term still so many grey areas!! I'm sure in time it gets easier and second nature and you learn by trial and error but holy this constant uncertainty is super annoying haha.