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    Can Bloodsucking Parasites Help Treat Asthma and Celiac Disease?


    Jefferson Adams


    • Hookworms have shown promise in treating celiac disease, and now research shows they might help treat asthma.


    Image Caption: Hookworms might yield treatments for celiac disease and asthma. Photo: Wiki Media Commons.

    Celiac.com 11/30/2016 - Trials using hookworm as a possible treatment for celiac disease are already underway in Australia, but they latest hookworm news indicates that they might also be useful for treating asthma.


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    The New World hookworm, aka necator americanus, is long and slender as an angel hair noodle. Adults are large enough to be seen with the naked eye. Seen up close, they look more like the sand worms in the movie Dune than anything people are used to seeing here on earth.

    Researchers are reporting that a protein produced by hookworms reduces the symptoms of asthma in mice, and could one day be used to treat asthma in humans, says the journal Science Translational Medicine. These parasites are some of the most maligned creatures in the animal kingdom. They chew into the human intestinal wall and suck blood to survive, but they just might be the key to making millions of people healthier.

    Says Severine Navarro, the paper's lead author and a senior research fellow at James Cook University in Australia, data from immunological studies shows that populations with no parasites also have "the highest incidence of autoimmune diseases and allergies." The data in this study arose from an effort by Navarro and her fellow researchers to look for a connection between success of de-worming programs around the world and the rise of immune system problems like asthma and celiac disease.

    Among other things, when hookworms infect humans, they secrete chemicals that turn off the immune alarm bells and repair the tissue around it. The worms limit blood consumption to a few drops a day and keeps its own numbers in check by plants offspring in the host's poop to ensure an orderly exit from the body.

    Navarro and her team wonder if the hookworm's stealthy adaptations also benefit their host by controlling in adverse immune reactions. The team's initial small study of one dozen trial participants showed that the hookworm did improve their tolerance of gluten.

    Since infecting large numbers of patients directly with hookworm might lead to other issues, the team isolated the active ingredient in hookworm spit - a compound called AIP-2 - and injected it into asthmatic mice on a daily basis for five days. Results showed a sharp decline in asthma symptoms, and reduced inflammation in airways. These benefits persisted for 10 weeks after the mice stopped getting the treatment.

    The researchers also noticed that AIP-2 seemed to have a calming effect on the body's dendritic cells - a part of the immune system responsible for processing threats. According to Navarro, the drug works by "basically rewiring the cells in that tissue into promoting very efficient regulatory T cells." This suggests that AIP-2 might also help humans, since dendritic cells have the same function in us that they do in mice.

    Navarro said the team's next step is a phase one clinical trial, which would test the effectiveness of an AIP-2 pill. Successful phase one trials will lead the way toward a safe drug that could help tens of millions of asthma sufferers. As seen in earlier studies using hookworm, the compound might be useful in treating autoimmune disorders, like celiac disease, inflammatory bowel disease and multiple sclerosis.

    Read more on hookworms and celiac disease.

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    Guest Catherine

    Posted

    Very interesting. I wondered when I read another related article if there was a correlation between "cleaning up" our bodies and a higher incidence of celiac disease. I think we have created problems for ourselves by being so germ phobic.

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  • Related Articles

    Jefferson Adams
    Celiac.com 11/16/2009 - Could unknown benefits from one of the oldest parasites of the human digestive tract hold the key to cure for celiac disease?
    Australian scientists think so. Encouraged by successful treatments of Crohn's and ulcerative colitis by American researchers using a pig whipworm (Trichuris sues), a team of Australian researchers is recruiting volunteers with celiac disease for trials using human hookworm (Necator americanus).
    The researchers have undertaken a similar preliminary study using a human hookworm in Crohn's patients.
    Researchers hypothesize that the disappearance of intestinal parasites from humans in developed countries may be responsible for the upsurge in many diseases including Celiac Disease, Crohn's, ulcerative colitis, asthma and hay fever.
    Using a small group of healthy people with celiac disease, the investigators will look to see if human hookworm interferes with the human immune reaction to gluten.
    Parasites survive partly by interfering with the host's immune response. The mechanisms they use to accomplish this are similar to those required by a person to regulate against the so-called autoimmune disorders, wherein the body begins to fight against itself.
    The investigators suspect that when parasites are excluded from the environment, some individuals become sufficiently self-reactive to develop an autoimmune disease.
    Using a small group of healthy people with celiac disease, the investigators will test if a human hookworm, Necator americanus, inhibits immune responsiveness to gluten.
    Specifically, they will examine whether hookworm infection will change the immune processes and suppress gluten sensitivity in people with celiac disease.
    Celiac disease is a good model for studying Crohn's disease because both involve similar immune changes. However, celiac patients are usually healthier overall, and, importantly, are not taking powerful immune suppressive drugs, and the provocative antigens (molecules that engage the immune system and provoke the disease) are well known and can be administered or cut out at will.
    In addition to directly benefitting celiac disease sufferers, this study may provide potential guidance in the use of hookworms to control inflammatory bowel disease.
    The study is open to people with proven celiac disease who reside in Brisbane, Australia. Those who enroll will be required to avoid gluten for six months.
    The blinded study will compare disease activity and immunity after a controlled break from the gluten-free diet in celiac patients, before and after hookworm infection.
    The team will use conventional and experimental methods to examine the disease severity and the immune system of celiac subjects before and after being inoculated with N. americanus.
    They will then compare immunity levels of the study subjects
    against those of matched, celiac control subjects (not infected with hookworm), before and after eating four pieces of standard white bread each day for three to five days.
    The initial study group will be small. The researchers will recruit ten subjects for each arm of the study, for a total of twenty.
    Initially, ten larvae will be placed on the skin under a light dressing for thirty minutes, followed by five more after twelve weeks.
    The researchers intend to asses whether the hookworm infection will change the immune processes and suppress gluten sensitivity in people with celiac disease. Outcomes to be measured will be those that reflect the activity of celiac disease.
    Stay tuned to see if hookworm therapy will be coming to a gastroenterologist near you! Tell us what you think. Would you sign up? Comment below.
    Source:
    ClinicalTrials.gov


    Jefferson Adams
    Celiac.com 03/30/2012 - A company called Microtest Laboratories is manufacturing doses of what they claim may be the first effective vaccine treatment for celiac disease. At this point, the only treatment for celiac disease is to avoid gluten in the diet.
    Other companies are working on vaccines for celiac disease, and several working trials are underway. However, this new drug's creator, ImmusanT, based in Cambridge says that, unlike other vaccines, which prevent an infection, their drug, Nexvax2 works by changing the immune system so it no longer attacks gluten.
    Production on Nexvax2, began last week, Steven G. Richter, Microtest’s president and science director, told a local reporter. So far, ImmusanT has raised $20 million in investor capital to bring the vaccine to market.
    Regarding the path from concept to manufacturing for Nexvax2, Richter says that the process has been anything but straightforward. "It's arty process," he told a local reporter, "you have to develop protocols for all the manufacturing and plans to do all of the work aseptically. You have to get all those protocols and plans approved through the regulatory process. Then you have to do the work.”
    Microtest is initially manufacturing 9,000 vials for ImmusanT: two 3,000-dose batches of vaccine and a 3,000-dose batch of inert placebo to be used in the clinical trial. Richter says that the control group contains everything except the active vaccine.
    ImmusanT is looking to start the first clinical trials in the second quarter of this year by testing the doses on people with celiac disease. The full article, in Massliveonline.com quotes Leslie J. Williams, president and CEO of ImmusanT, as saying that “The test will be if it [the vaccine] induces a tolerance for gluten in the diet."
    The report says that Williams and the company hope to get the vaccine commercially available by 2017. Will the company succeed? Will they have a successful vaccine available in just five short years? Let us know what you think.


    Jefferson Adams
    Celiac.com 04/10/2015 - Of course, a strict gluten free diet is still the only safe and effective treatment for celiac disease. However, new drugs in development, some of which are currently being tested on humans, might allow people with celiac disease to safely eat gluten again, at least in small amounts.
    To be fair, even if all goes smoothly, it will be a few years at least before we see such treatments on the market. Moreover, even though many early results have been encouraging, none have yet entered safety trials, the final step before Food and Drug Administration approval and commercial availability.
    Drugs currently under trial include an enzyme that splits the protein in wheat that triggers adverse reactions, into smaller harmless products, and another which promises to make the gut less leaky, and thus block potentially toxic substances from triggering inflammation.
    There are several other drugs in earlier stages of development aimed at suppressing the immune response to gluten and preventing intestinal inflammation:
    ALV003, which will protect people with celiac disease against gut damage from small amounts of gluten. BL-7010 is a novel co-polymer for the treatment of celiac disease, which significantly reduces the immune response triggered by gluten. ImmusanT’s therapeutic vaccine Nexvax2 combines three proprietary peptides that elicit an immune response in celiac disease patients who carry the immune recognition gene HLA-DQ2. Larazotide acetate (AT-1001) is Alba Therapeutics Corporation’s investigational product, a first-in-class tight junction regulator, intended for the treatment of patients with celiac disease. AVX176, from Avaxia Biologics, is an investigational oral antibody drug that is the subject of U.S. composition of matter patent 8,071,101, “Antibody Therapy for Treatment of Diseases Associated with Gluten Intolerance.” The patent, which expires on May 27 2029, provides broad coverage for treating celiac disease using orally administered antibodies produced by Avaxia’s proprietary platform technology [32]. ActoGenX is carrying out discovery research in celiac disease with its range of ActoBiotics™, which use Lactococcus lactis as an expression system to locally secrete bio-therapeutics such as cytokines, antibodies, hormones, etc. Chemocentryx’s CCR9, is also known as Traficet-EN, or CCX282B), and was originally intended for patients with moderate-to-severe Crohn’s disease. It has completed one Phase 2 trial in 67 patients with celiac disease. Meanwhile, in Europe, Dr. Falk Pharma and Zedira recently announced the start of phase I clinical trials for the drug candidate ZED1227, a direct acting inhibitor of tissue transglutaminase. The small molecule targets the dysregulated transglutaminase within the small intestine in order to dampen the immune response to gluten which drives the disease process.
    Some of these drugs may be taken right before eating gluten, while others might be more effective when taken on a regular schedule. If approved for use as intended, these drugs will likely allow people with celiac disease to eat gluten in small amounts. To my knowledge, there is no drug in current trial phases that is designed to permit unrestricted gluten consumption.
    So, the good news is that the next few years may see commercially available treatments that might actual help people manage celiac disease. The downside for people with celiac disease, at least for now, is that there is no treatment on the horizon that will allow safe, unlimited gluten-consumption. Moreover, there is no hint that a cure is coming anytime soon.
    Still, it’s good to know that researchers are working on providing helpful tools for treating celiac disease.
    Are you looking forward to seeing new treatment options for celiac disease? What kind of benefits should such treatments offer?
    Source:
    Gastroenterology Report

    Jefferson Adams
    Celiac.com 07/19/2016 - The world's first vaccine aimed at curing celiac disease is slated to begin full trials later this year, and residents of the Australian state of Victoria will be among the first humans to give it a try against celiac disease.
    The vaccine, called Nexvax2, was developed by Australian scientist Dr Bob Anderson, and is aimed at giving celiac patients a chance to overcome their immune reaction to the gluten found in products containing wheat, rye and barley. Nexvax2 aims to de-sensitise patients to three peptides contained in gluten that trigger a damaging reaction in their immune system.
    Previous trials on 150 patients from Melbourne, Perth, Adelaide, Brisbane and Auckland were aimed at finding a safe dosage rather than assessing its ability to beat celiac disease. Results from those favorable earlier trials were released in May, and Dr Anderson says that the larger phase II study, also being undertaken in the US and Europe, will assess how well the vaccine works against celiac disease.
    Dr Anderson first identified the peptides triggering coeliac disease and began developing the vaccine while working at Melbourne's Walter and Eliza Hall Institute, before travelling to Boston for six weeks as part of a sister city arrangement through the City of Melbourne, where he made contact with ImmusanT to further the discovery.
    This is certainly exciting news for people with celiac disease, many of whom may benefit from such treatment.
    Stay tuned for news on the progress of these trials.
    Source:
    dailysecrets.press

  • 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