• Join our community!

    Do you have questions about celiac disease or the gluten-free diet?

  • Ads by Google:
     




    Get email alerts Subscribe to Celiac.com's FREE weekly eNewsletter

    Ads by Google:



       Get email alertsSubscribe to Celiac.com's FREE weekly eNewsletter

  • Member Statistics

    77,473
    Total Members
    3,093
    Most Online
    hayley stan
    Newest Member
    hayley stan
    Joined
  • 0

    Untreated Celiacs at Increased Risk of Cerebral Hypoperfusion


    Scott Adams


    Ads by Google:




    ARTICLE CONTINUES BELOW ADS
    Ads by Google:



    Am J Med 2004;116:312-317.

    Italian researchers have concluded that as many as 73% of patients with untreated celiac disease have at least one brain region that is hypoperfused (the blood vessels are damaged), although the condition is rare in the non-celiac and treated celiac disease populations. Dr. Giovanni Addolorato, from the Catholic University in Rome, and colleagues looked at 15 untreated and 15 treated (on gluten-free diets) celiac disease patients and compared them with 27 healthy controls. They found that 11 (73%) of the untreated celiac disease patients exhibited hypoperfusion in at least one cerebral region, when only one treated patient and no controls had the problem. Additionally they found that in 7 of the 26 brain regions that they looked at, blood flow was significantly lower in untreated patients than in controls, and no blood flow differences were detected between the treated group and the control group.

    According to the researchers the cause of the vascular brain damage in celiac disease is unclear at this point, but it may be related to the increased intestinal blood flow, and/or endothelial inflammation caused by the autoimmune disease, perhaps involving antigliadin antibodies or unidentified neurotoxic antibodies.

    0


    User Feedback

    Recommended Comments

    Guest Zoe Langley

    Posted

    This article and this web site are just great for getting timely and much needed information about gluten sensitivity.

    Share this comment


    Link to comment
    Share on other sites


    Your content will need to be approved by a moderator

    Guest
    You are commenting as a guest. If you have an account, please sign in.
    Add a comment...

    ×   Pasted as rich text.   Paste as plain text instead

      Only 75 emoji are allowed.

    ×   Your link has been automatically embedded.   Display as a link instead

    ×   Your previous content has been restored.   Clear editor

    ×   You cannot paste images directly. Upload or insert images from URL.


  • Popular Contributors

  • Ads by Google:

  • Who's Online   6 Members, 0 Anonymous, 258 Guests (See full list)

  • Related Articles

    Scott Adams
    Nerve Disease and Celiac Disease
    Celiac.com 02/08/1996 - The article was based on a study published in the same weeks Lancet which was conducted by Dr. Marios Hadjivassiliou and colleagues at the Royal Hallamshire Hospital in Sheffield, England. Dr. Hadjivassiliou tested patients with various undiagnosed neurological symptoms and found that 57% of them tested positive to gluten sensitivity. Specifically, they tested positive for gliadin antibodies, which means they have gluten sensitivity and not necessarily celiac disease. Sixteen percent of the patients were found to have full blown celiac disease, which is far higher than the estimated .004% level found in the normal population. Five percent of the patients with previously diagnosed neurological disorders such as Parkinsons disease were found to have the gliadin antibodies present compared to 12% of a healthy control group.
    According Dr. Hadjivassilious theory, many neurological ailments could be caused when the anti-gliadin antibodies mistakenly attack neural tissue and destroy it. The fact that some celiac patients with neural damage never fully heal helps to support Dr. Hadjivassilious theory, because neural tissue repairs itself very slowly, if at all. Further, Dr. Hadjivassiliou states in the article that celiac disease seems to be much more common than was previously thought (1 in 250 people). When one includes the people who test positive for the gliadin antibody (this means they have gluten-sensitivity and are not necessarily celiacs), the amount could be much higher than 1 in 250. Based on his study, Dr. Hadjivassiliou recommends that patients who exhibit any type of neural disorders be tested for gluten sensitivity and celiac disease.

    Jefferson Adams
    Celiac.com 09/02/2008 - Thanks to a team of  researchers based in Great Britain, doctors may soon have a powerful new diagnostic tool to help them in their efforts to combat the damage caused by celiac disease. Their new discovery concerns people with celiac disease who may also develop neurological disorders.
    The research team was made up of Marios Hadjivassiliou, MD, Pascale Aeschlimann, BSc, Alexander Strigun, MSc, David Sanders, MD, Nicola Woodroofe, PhD, and Daniel Aeschlimann, PhD.  The team recently investigated the nature of gluten sensitivity by isolating a unique neuronal transglutaminase enzyme and examining whether it is the focus of the immune response in celiac patients with neurological dysfunction.
    About one in ten people with celiac disease also suffer from associated neurological disorders, mainly from a condition involving the cerebellum called gluten ataxia, and another involving the peripheral nerves called gluten neuropathy. For many people celiacs with gluten ataxia, their neurological problems are their sole symptom. Only about 1 out of 3 people with gluten ataxia and celiac disease will show classic intestinal damage when given a biopsy. This can make proper diagnosis difficult for them. Also, there’s presently no reliable way to predict which people with gluten intolerance might develop neurological problems.
    Most people familiar with celiac disease know that gastrointestinal discomfort is one of the most common symptoms. The antibody most commonly associated with such discomfort is called anti-transglutaminase 2 IgA. This is one of the main antibodies that doctors commonly look for when evaluating possible cases of celiac disease. Anti-TG2 antibodies are pretty much exclusive to people with celiac disease, and are associated with both untreated clinically symptomatic celiac disease, and with the latent form of the disease. This makes the presence of anti-TG2 antibodies an excellent diagnostic indicator of celiac disease.
    Anti-TG2, however, may not be the best indicator in every case of celiac disease. One example is in cases of dermatitis herpetiformis, which is an external skin reaction to gluten. Most people with dermatitis herpetiformis have a persistent itchy skin rash, and while the majority of cases show intestinal damage with a biopsy, patients rarely experience intestinal discomfort associated with classic celiac disease.1 There is also reliable data that point to a role that anti-TG3 plays in cases of dermatitis herpetiformis.2 This indicates that the nature of a given individual’s immune response may determine how celiac disease manifests itself within that individual.
    That hypothesis seems to be born out by the research team’s discovery that another antibody, called anti-transglutaminase 6 IgG and IgA response is widespread in gluten ataxia, completely outside of any intestinal symptoms. These antibodies are not found in healthy control patients or in patients with neurological conditions that had clear genetic causes. Both groups showed no anti-TG6 in their blood samples.
    The research team took blood samples from 20 patients with newly diagnosed celiac disease before the patients began a gluten-free diet. The team confirmed the presence of celiac disease with duodenal biopsy and made sure the patients had no patients had no evidence of neurological problems.
    The team then took blood samples from 34 patients with Gluten Ataxia, which they defined as otherwise sporadic idiopathic ataxia with positive IgG and/or IgA anti-gliadin antibodies.
    The also took samples from another17 patients with peripheral idiopathic neuropathy (PN) who tested positive for anti-gliadin antibodies. These 17 patients tested negative for anti-MAG and anti-GM1 and had no evidence of intestinal damage on biopsy.
    The team used three separate control groups. The first was a group with genetic ataxia, which included 18 patients with ataxia that was genetic in nature, or with a clear family history of autosomal dominant ataxia. The second control group of 14 patients included cases of diseases that were immune-mediated, but not tied to gluten-sensitivity (such as vasculitis, viral cerebellitis, paraneoplastic ataxia, GAD ataxia). Lastly, the team used blood samples from 19 healthy individuals as another control group.
    The research team used recombinant human transglutaminases to develop ELISA and inhibition assays with which they measured blood samples of patients with gluten sensitive gastrointestinal and neurological disorders, along with several control groups that included unrelated inherited or immune conditions, for the presence and specificity of autoantibodies.
    The team found that the blood samples of patients with celiac disease and gluten ataxia contain IgA and IgG class antibodies to TG6 that are not present in the healthy control patients or in patients with neurological conditions that had clear genetic causes.
    At present, doctors test for celiac disease by checking the HLA type, and looking for the presence of anti-gliadin and anti-transglutaminase 2 antibodies. The results of this study indicate that the presence of anti-transglutaminase 6 can help to pinpoint patients with gluten sensitivity that may be at risk of developing neurological disease.
    Forthcoming: Annals of Neurology
    Footnotes:
    1. Marks J, Shuster S, Watson AJ. Small bowel changes in dermatitis herpetiformis. Lancet 1966; 2:1280-1282.
    2. Sárdy M, Kárpáti S, Merkl B, Paulsson M, and Smyth N. Epidermal transglutaminase (TGase3) is the autoantigen of Dermatitis Herpetiformis. J Exp Med 2002; 195:747-757.


    Jefferson Adams
    Celiac.com 02/09/2009 - Doctors are recommending simple, low-cost blood tests to screen for celiac disease in patients who have Restless Leg Syndrome (RLS) with low serum ferritin, but who otherwise show no clear cause for iron deficiency.
    Low iron reserves are a known risk factor Restless Leg Syndrome, as blood iron levels below 45-50ng/mL have been tied to more severe expressions of RLS. In fact, iron levels are so important to assessing RLS, that it is now common for doctors to test blood ferritin levels when first assessing Restless Leg Syndrome. Celiac disease is a common genetic disorder of the immune system that can cause iron deficiency.
    Doctors S. Manchanda, C.R. Davies, and D. Picchietti of the College of Medicine at the University of Illinois at Urbana-Champaign recently set out to determine if celiac disease might play a role in iron deficiency in patients with Restless Leg Syndrome.
    The doctors evaluated a series of four patients with Restless Leg Syndrome and blood ferritin below 25ng/mL, who had shown positive blood tests for celiac disease. Doctors confirmed celiac disease for all four patients via duodenal biopsy and positive reaction to a gluten-free diet. In each case, Restless Leg Syndrome symptoms improved, with two patients discontinuing Restless Leg Syndrome medication and two responding positively without medication.
    The doctors are recommending simple, low-cost blood tests to screen for celiac disease in patients who have Restless Leg Syndrome with low serum ferritin, but who otherwise show no clear cause for iron deficiency.
    They also note that diagnosis and treatment of celiac disease is likely to improve the outcome for those patients with Restless Leg Syndrome, as well as to better identify people at risk for the significant long-term complications associated with celiac disease.
    Restless Leg Syndrome is just the latest neurological disorder to show a connection to celiac disease. Stay tuned as more information  becomes available.

    Source: Sleep Med. 2009 Jan 10. PMID: 19138881

    Jefferson Adams
    Celiac.com 03/20/2014 - No one wants a brain disease, and some recent books on the effects of gluten-free diets are suggesting that a gluten-free diet might actually protect you from brain diseases.
    One such book is Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar — Your Brain's Silent Killers, by David Perlmutter, M.D., a practicing neurologist.
    Symptoms of celiac disease are known to include intestinal difficulties associated with an adverse immunological response triggered by gluten. This response, which leads to inflammation in the gut, can happen elsewhere in the body too.
    According to Perlmutter, inflammation is at the root of many diseases and complications, including, brain decay.
    According to Perlmutter, gluten can lead to inflammation in the brain, which he believes leads to conditions like dementia and Alzheimer's.
    Perlmutter says that gluten, by triggering the immune system, causes inflammation in the brain, which promotes the brain's glycation by circulating blood sugar. Gram for gram, wheat raises blood sugar levels more than sugar itself.
    Perlmutter encourages strong dietary changes that have drawn some criticism. Specifically, he has recommended an intake of 60 or fewer grams of carbohydrate per day.
    Some point out potential negative health consequences of a high-fat, low-carb diet, both in healthy people and for those with specific conditions, like adrenal or thyroid issues.
    However, Perlmutter's take on brain glycation, in which gluten triggers an immune response in certain people, contributing to inflammation, and to inflammatory disease, such as diabetes and Alzheimer's, may have some foundation. 
    Perlmutter is a reputable neurologist, so his opinion and insight go beyond anecdotal evidence and speculation. It will be interesting to see how much of his perspective is borne out by science. Meantime, Perlmutter certainly makes for interesting, thought-provoking reading.
    What's your experience? Has going gluten-free made an impact on your brain function and awareness?
    Read more at: Celiac.com and at Medical Express.com.

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/19/2018 - Could baking soda help reduce the inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease? Scientists at the Medical College of Georgia at Augusta University say that a daily dose of baking soda may in fact help reduce inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease.
    Those scientists recently gathered some of the first evidence to show that cheap, over-the-counter antacids can prompt the spleen to promote an anti-inflammatory environment that could be helpful in combating inflammatory disease.
    A type of cell called mesothelial cells line our body cavities, like the digestive tract. They have little fingers, called microvilli, that sense the environment, and warn the organs they cover that there is an invader and an immune response is needed.
    The team’s data shows that when rats or healthy people drink a solution of baking soda, the stomach makes more acid, which causes mesothelial cells on the outside of the spleen to tell the spleen to go easy on the immune response.  "It's most likely a hamburger not a bacterial infection," is basically the message, says Dr. Paul O'Connor, renal physiologist in the MCG Department of Physiology at Augusta University and the study's corresponding author.
    That message, which is transmitted with help from a chemical messenger called acetylcholine, seems to encourage the gut to shift against inflammation, say the scientists.
    In patients who drank water with baking soda for two weeks, immune cells called macrophages, shifted from primarily those that promote inflammation, called M1, to those that reduce it, called M2. "The shift from inflammatory to an anti-inflammatory profile is happening everywhere," O'Connor says. "We saw it in the kidneys, we saw it in the spleen, now we see it in the peripheral blood."
    O'Connor hopes drinking baking soda can one day produce similar results for people with autoimmune disease. "You are not really turning anything off or on, you are just pushing it toward one side by giving an anti-inflammatory stimulus," he says, in this case, away from harmful inflammation. "It's potentially a really safe way to treat inflammatory disease."
    The research was funded by the National Institutes of Health.
    Read more at: Sciencedaily.com

    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
    The research team included P Singh, A Arora, TA Strand, DA Leffler, C Catassi, PH Green, CP Kelly, V Ahuja, and GK Makharia. They are variously affiliated with the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Lady Hardinge Medical College, New Delhi, India; Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA; Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York; and the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
    For their review, the team searched Medline, PubMed, and EMBASE for the keywords ‘celiac disease,’ ‘celiac,’ ‘tissue transglutaminase antibody,’ ‘anti-endomysium antibody,’ ‘endomysial antibody,’ and ‘prevalence’ for studies published from January 1991 through March 2016. 
    The team cross-referenced each article with the words ‘Asia,’ ‘Europe,’ ‘Africa,’ ‘South America,’ ‘North America,’ and ‘Australia.’ They defined celiac diagnosis based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. The team used 96 articles of 3,843 articles in their final analysis.
    Overall global prevalence of celiac disease was 1.4% in 275,818 individuals, based on positive blood tests for anti-tissue transglutaminase and/or anti-endomysial antibodies. The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% in 138,792 individuals. That means that numerous people with celiac disease potentially remain undiagnosed.
    Rates of celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was 0.6% in female vs 0.4% males. Celiac disease was significantly more common in children than adults.
    This systematic review and meta-analysis showed celiac disease to be reported worldwide. Blood test data shows celiac disease rate of 1.4%, while biopsy data shows 0.7%. The prevalence of celiac disease varies with sex, age, and location. 
    This review demonstrates a need for more comprehensive population-based studies of celiac disease in numerous countries.  The 1.4% rate indicates that there are 91.2 million people worldwide with celiac disease, and 3.9 million are in the U.S.A.
    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023