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TCRβ Clonality Improves Diagnostic Yield of TCRγ Clonality in Refractory Celiac Disease

Celiac.com 04/02/2012 - A team of researchers recently set out to assess diagnostic yield of Vβ and Vγ clonality in refractory celiac disease (RCD). The team set out to verify whether analyzing both TCRβ and TCRγ clonality in duodenal biopsies from RCD patients improves diagnostic accuracy.

Photo: CC--kinshuksunilThe research team included Vittorio Perfetti, Laura Brunetti, Federico Biagi, Rachele Ciccocioppo, Paola I. Bianchi, and Gino R. Corazza. They are affiliated with the Coeliac Centre/First Department of Internal Medicine, and the Department of Medical Oncology at the Fondazione IRCCS Policlinico San Matteo of the University of Pavia in Italy.

Refractory celiac disease is what is known as a pre-neoplastic condition, because many patients develop a kind of cancer called enteropathy-type T-cell lymphoma, which is a mature T-cell receptor α-β lymphoma that forms in the gut, and is often fatal.

Recent research has been directed at a variety of intraepithelial intestinal lymphocytes. Polymerase chain reaction (PCR) analysis and sequencing shows that these lymphocytes both express the same lymphoma T-cell receptor variable region (V)γ.

Also, the Biomedicine and Health-2 Concerted Action has created standardized, highly specific, and sensitive PCR assays for both Vγ and Vβ.

The team set out to verify whether analyzing both rearrangements in duodenal biopsies from RCD patients increases the diagnostic accuracy of this method.

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For the study, the team analyzed duodenal biopsies from 15 RCD patients, 21 negative controls, and 2 positive controls with enteropathy-type T-cell lymphoma complicating celiac disease.

The them conducted multiplex clonality analyses using Biomedicine and Health-2 protocols. They cloned and sequenced PCR products.

They found monoclonal rearrangements in 5/15 samples from patients with RCD, two of which showed both rearrangements, two which showed Vβ, and just one Vγ clonality.

Monoclonality was found in 4/8 of the RCD patients who subsequently died, whereas only 1/7 of the patients still alive presented a monoclonal rearrangement. Positive controls revealed both monoclonal rearrangements; rearrangements were not detected in 20 of 21 negative controls. Sequencing of the amplified fragments confirmed the results.

Results showed that the combined analysis of both TCRβ and TCRγ rearrangements allowed recognition of monoclonal populations in patients who otherwise tested negative. Overall detection rates increased from 20%(Vγ only) to 33%(Vγ and Vβ),

Increasing detection in patients who would otherwise test negative increases chances of early identification of RCD patients at high risk of death.

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1 Response:

 
Helen Rank
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said this on
12 Apr 2012 2:57:43 PM PDT
Very informative. This will give me some questions to ask the alergist. His celiac test came back negative. He has been on a gluten and milk free diet now for about 2 1/2 to three years. He still has problems with corn and pinto beans. I will not change his diet until we know what is going on with him. He is only 5 years old. When he was an little baby he couldn't keep his formula down. He was finally put on fresh goat's milk. That helped a little bit. But then he started to throw it up also. I hope that we can find what is making his so sick. I think the next Dr. is going to be an G.I. specialist's.




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I use almond, and coconut a lot now my bakery used to use oat and almond blends. We never used rice, or starches as our goal was to keep it low glycemic. Now days we are transitioning to cut out oats. I started having....ok I omitted and gave in after being in denial a similar reaction to oats (10% of celiacs do if I recall) over a year ago. Anyway as for flour blends premade avoiding rice and grains try simple mills at https://www.simplemills.com/collections/all I have composed a huge list of various gluten-free goods here, even recently updated with grain free, and pizza section https://www.celiac.com/gluten-free/topic/117090-gluten-free-food-alternatives-list/

Hello Everyone, New here and have joined because I couldn't find an answer to my question online. I was diagnosed after a long spell with anemia in 2015 and have been on the diet (and improving!) ever since. But I wonder whether how much rice I'm eating is very healthy. I have always liked to bake and it took awhile to find a flour mix I like (Cup 4 Cup - worth its weight in gold...), but a lot of gluten-free food subs in rice (white rice, brown rice, rice flour) plus I eat actual rice as a side dish. Is this too much? Keep in mind, I also eat salads like it's my job and love making vegetable soups too. Any advice on gluten-free foods (specifically flours) that don't fall back on rice as a substitute? I should add that I can't really get excited about quinoa, despite my best efforts. Thanks in advance.

I would say get retested, to be sure, do a gluten challenge with her where she eats gluten for 12 weeks, not much just a half slice of bread a day or a wheat cracker for the blood test and 2 weeks for the biopsy. You mentioned bumps, and dry patches...this might be DH from celiacs and if it is you can go to a dermatologist and they can test it. In some people with DH reactions to gluten, their intestines do not show much damage as most of the antibodies are directed elsewhere. In this case you would have your symptoms. Now Celiac is a autoimmune disease that commonly has other auto immune diseases associated with it. NOW if your daughter has the gene for it she could have another automimmune disease I am not very familiar with and someone else might be able to help you more on suggestions for testing. Now in my personal opinion it sounds like she was still getting into gluten when you said she was off of it. NOTE gluten is a tricky bugger, it is a protein smaller then a germ that can stick in cracks and scratches on all your utensils, food prep area, knifes, etc. As a flour it can hang in the air for hours and even be inhaled effecting some of us. It is present in a lot of things we do not consider, like makeup, playdough, shampoos, seasonings, sauces, even some dry wall spackles. Now if she is in a shared house hold with other kids and not everyone is on this diet she has likely been getting into gluten somewhere, like touching glutened surfaces the other kids touched after eating gluten foods then putting her hand in her mouth or on safe foods. Or just randomly eating gluten foods, note symptoms can last weeks and wane from how it is effecting you. It does not take much to trigger symptoms you might have to be more careful and move her to a whole foods only diet, and have a separate prep area, utensils, cooking zone for her if you wish to keep fixing separate meals for her vs the gluten family. I would suggest just changing the entire family over, anyway perhaps start with a separate fold out table, use freezer paper to line the prep area, a microwave, mini toaster oven, and some microwave cook ware like steamers, steam bags, etc. and using gloves to fix her meals. She will need her own condiment jars (crumbs in hte jars) and area for safe snacks. I would suggest getting her only gluten-free CERTIFIED FOODS for now. You can find some whole food healthy snacks at mygerbs.com, and a few other places. I will provide a link to gluten-free food list. PERHAPS you can change the entire family over....now days it is more like changing brands as everything you used to eat is available in a gluten-free brand. ALSO have a lot of dairy free options there. https://www.celiac.com/gluten-free/topic/117090-gluten-free-food-alternatives-list/

Hi wondering if someone could help. my daughter has mildly raised TTG levels and the gliadine levels, she has one Coeliacs gene, but her biopsy came back negative. We have kept her off gluten (and low dairy) for nearly a year to see if her symptoms improved. They haven't. But I don't know if they are related to gluten specifically. Just wondering if anyone has other suggestions that may be going on with her. Her symptoms are: - Short stature, she's nearly 9 and my 6 year old boy is nearly bigger than her - bumps on back of her arms - urine leaking and occasional soiled pants, which could be from constipation she has at time's - sticking out stomach - dry patchy rashes on her face - joint pain sporadically - vomits every 6 weeks, but hasn't had gluten and seems to be no food connection - reoccurring thrush She had gluten last night at a party and was fine today. I'm a bit lost and not sure where else to turn. Thanks for any help.

We have gone gluten free, our whole house, as of a month ago. It was pretty seamless since I had been gluten-free for 5 months last year. I have found many good recipes, and my picky husband and one of my boys who is also a picky eater, even prefer many gluten-free recipes to the regular ones. My husband did see my point about the size of the gluten protein means nothing. Its a gluten protein period, that's what you are avoiding. It doesn't matter if its hiding in the scratch of your baking sheet and you can't see it. You can't see the wind, but it's still there. I hear you on the anemia. I've been anemic for several years, I just thought it as because I was getting a little older. Has your anemia gone away or do you still have problems with it?