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    Celiac Disease First: Researchers Identify a Role for Main Inherited Genetic Variation


    Jefferson Adams

    Celiac.com 08/20/2009 - For the first time, a team of celiac disease researchers has discovered a role for the main inherited celiac-associated genetic variation, connecting altered NF-kB signalling with risk variants associated with Celiac disease in TNFAIP3 and REL.


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    The research team was made up of G. Trynka, A. Zhernakova, J. Romanos, L. Franke, K. A. Hunt, G. Turner, M. Bruinenberg, G. A. Heap, M. Platteel,1 A. W. Ryan, C. de Kovel, G. K. T. Holmes, P. D. Howdle, J. R. F. Walters, D. S. Sanders, C. J. J. Mulder, M. L. Mearin, W. H. M. Verbeek, V. Trimble, F. M. Stevens, D. Kelleher, D. Barisani, M. T. Bardella, R. McManus, D. A. van Heel, C. Wijmenga.

    An earlier celiac disease genome-wide association study (GWAS) identified risk variants in the human leucocyte antigen (HLA) region and eight new risk areas.

    To find more celiac disease locations, the research team chose to examine 458 single nucleotide polymorphisms (SNPs) that exhibited weaker ties in the GWAS for genotyping and analysis in four independent cohorts. The 458 SNPs were found among 1682 cases and 3258 controls from UK, Irish and Dutch populations.

    The team combined the results with the original GWAS cohort involving 767 UK cases and 1422 controls), in which six SNPs showed association with p,1610. Those six were then genotyped in an independent Italian celiac cohort (538 cases and 593 controls). The research team found two new celiac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL).

    In the final combined analysis of all 2987 cases and 5273 controls, both regions achieved genome-wide significance (rs2327832 p=1.3610, and rs842647 p=5.2610).

    The researchers used RNA isolated from biopsies and from whole
    blood RNA to look at gene expression. They observed no changes in either gene expression, or in the correlation of genotype with gene expression.

    From these results, the research team concluded that both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kB) inflammatory signalling pathway.

    For the first time, researchers have identified a role for main inherited variation in this important biological pathway that predisposes individuals to celiac disease.

    Currently, the HLA risk factors and the 10 established non-HLA risk factors provide an explanation for about 40% of inheritance factors for celiac disease.

    Clearly, more research is needed to isolate the other 60% of inheritability factors for celiac disease. Success in this very important area promises to open up the understanding of celiac disease, and to help speed new treatments, and possibly a cure.


    Gut 2009;58:1078–1083.

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    Scott Adams
    Paul V, Henkerr J, Todt H, Eysold R.
    Z.Klin.Med., 1985; 40: 707-709.
    In this study 90 EEGs were performed on 58 celiac children. Researchers concluded that abnormal brain waves resulted from the ingestion of gluten by celiac children. They also concluded that a gluten challenge should not be given before a child reaches the age of 6 years old, and the challenge should not last longer than 5 months. The researchers main concern seems to be the risk of permanent brain damage that they believe could be caused in a celiac child who eats gluten for a prolonged period of time.

    Jefferson Adams
    Celiac.com 09/29/2011 - Results of various studies comparing mortality in undetected celiac disease compared with the general population have been contradictory. Some studies have suggested a fourfold increase in mortality compared with the general population, while others have found no increase at all.
    A research team set out to clarify the matter by crafting a cohort study of Cambridge doctors that would establish all-cause and cause-specific mortality in undiagnosed celiac disease, identified by anti-endomysial antibody (EMA) positivity.
    The team included C. Canavan, R. F. Logan, K. T. Khaw, and J. West. They are variously affiliated with the Division of Epidemiology and Public Health at University of Nottingham in Nottingham, UK, with the NIHR Biomedical Research Unit of the Nottingham Digestive Diseases Centre at Nottingham University Hospital in Nottingham, UK, and with the Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    For their study, the team chose their subjects from a general population aged 45-76 years in 1990.
    They then tracked all deaths using the Office for National Statistics. They calculated mortality rates per 1000 person year, making adjustments for age, gender, smoking and socioeconomic group using multivariate Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI).
    Results showed 117,914 patient years of follow-up from 7527 participants, with an average of 16.8 years.
    Eighty-seven patients suffered from undetected celiac disease, their all-cause mortality rate was 9.4 per 1000 person years (95% CI 5.4-16.1) compared with 12.7 (95% CI 12.1-13.4) in EMA-negative participants.
    The adjusted all-cause mortality hazard ratio was 0.98 (95% CI 0.57-1.69). Untreated celiac disease showed no increase in death due to cancer or circulatory diseases. Adjusted hazard ratios were 1.27 (95% CI 0.57-2.85) and 1.39 (95% CI 0.66-2.92) respectively.
    The research team found no higher overall mortality in people older than 45 years with undetected coeliac disease compared with the general population. They also found no increase in deaths related to circulatory disease or cancer.
    The team concludes that these results do not support routine screening people older than 45 years for celiac disease.
    Source:

     Aliment Pharmacol Ther. 2011 Aug 17. doi: 10.1111/j.1365-2036.2011.04811.x.

    Jefferson Adams
    Celiac.com 03/14/2012 - A group of researchers recently studied the ways in which HLA-DQ2 and DQ8 might influence the severity of celiac disease. Specifically, the team wanted to study HLA-DQA1 and DQB1 profiles in adults with different forms of celiac disease, including adults with complicated and potential celiac disease, the most seriously affected, and those with the best preserved histologic end of the pathologic celiac spectrum.
    The researchers included F. Biagi, P.I. Bianchi, C. Vattiato, A. Marchese, L. Trotta, C. Badulli, A. De Silvestri, M. Martinetti, and G.R. Corazza. They are affiliated with the Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy. 
    Patients with complicated celiac disease showed more HLA-DQB1*02 homozygosity than those with uncomplicated celiac disease.
    The team conducted HLA-DQA1 and DQB1 molecular typing for 218 adults with celiac disease. Of these, 169 had uncomplicated celiac disease, 27 had complicated celiac disease, and 22 had potential celiac disease. They used 224 healthy stem cell donors as a control group.
    The team analyzed HLA-DQA1 and DQB1 gene polymorphism using polymerase chain reaction sequence-specific primers and/or reverse polymerase chain reaction sequence-specific oligonucleotides. They found, as expected, that the frequency of HLA-DQB1*02 allele, DQB1*02 homozygosity, and DQB1*0302 gene were statistically different in the four groups.
    However, multivariate analysis showed that patients with potential celiac disease have a higher frequency of both HLA-DQB1*0302 and HLA-DQB1*0603 alleles, along with a reduced frequency of DQB1*02 homozygosity, as compared with patients with uncomplicated and complicated celiac disease.
    The increased frequency of DQB1*0302 coupled with the reduced frequency of DQB1*02 homozygosity in potential celiac disease supports the idea that variations in clinical/pathologic expressions of celiac disease might reflect different immune system triggers. This observation could impact the way in which celiac disease is understood and studied in the future.
    Source:

    J Clin Gastroenterol. 2012 Jan;46(1):46-50.

    Jefferson Adams
    Celiac.com 10/03/2014 - Celiac disease patients in Australia have shown a major improvement in gluten tolerance after receiving experimental hookworm treatments. The study is part of an effort to determine if parasitic helminths, such as hookworm, might help to treat inflammatory disorders, including celiac disease.
    In this case, the research team assessed the influence of experimental hookworm infection on the predicted outcomes of three escalating gluten challenges in volunteers with confirmed celiac disease.
    The research team included John Croese, MD, Paul Giacomin, PhD, Severine Navarro, PhD, Andrew Clouston, MD, Leisa McCann, RN, Annette Dougall, PhD, Ivana Ferreira, BSc, Atik Susianto, MD, Peter O'Rourke, PhD, Mariko Howlett, MD, James McCarthy, MD, Christian Engwerda, PhD, Dianne Jones, BHSc, and Alex Loukas, PhD.
    They are variously affiliated with the Department of Gastroenterology and Hepatology at The Prince Charles Hospital, Brisbane, Australia, the Center for Biodiscovery and Molecular Development of Therapeutics at the Australian Institute of Tropical Health and Medicine of James Cook University in Cairns, Australia, Envoi Specialist Pathologists in Brisbane, Australia, QIMR Berghofer Medical Research Institute in Brisbane, Australia, the Royal Brisbane and Women's Hospital, and with Logan Hospital, Brisbane, Australia.
    This particular study followed twelve adult volunteers with diet-managed celiac disease. The volunteers were inoculated with 20 Necator americanus (hookworm) larvae, and then consumed increasing amounts of gluten in the form of spaghetti.
    The volunteers first received 10 to 50 milligrams for 12 weeks (microchallenge); they then received 25 milligrams daily + 1 gram twice weekly for 12 weeks (GC-1g); and finally 3 grams daily (60-75 straws of spaghetti) for 2 weeks (GC-3g).
    The subjects were then evaluated for symptomatic, serologic, and histological outcomes of gluten toxicity. They were also examined for regulatory and inflammatory T cell populations in blood and mucosa. Two gluten-intolerant subjects withdrew after micro-challenge. Ten completed GC-1g, and eight of these ten volunteers enrolled in and completed the full course of the study.
    Most celiacs who are exposed to gluten challenge will show adverse changes in the intestinal villi, which is measured in terms of villous height-to-crypt depth ratios. Also, such patients will usually show an increase in blood antibodies, such as IgA-tissue transglutaminase, indiucating an adverse reaction to gluten. However, the results here showed that median villous height-to-crypt depth ratios (2.60-2.63; P = .98) did not decrease as predicted after GC-1g. Moreover, mean IgA-tissue transglutaminase titers declined, contrary to the predicted rise after GC-3g.
    Other results showed that quality of life scores improved (46.3-40.6; P = .05); while celiac symptom indices (24.3-24.3; P = .53), intra-epithelial lymphocyte percentages (32.5-35.0; P = .47), and Marsh scores remained unchanged by gluten challenge.
    Intestinal T cells expressing IFNγ were reduced following hookworm infection (23.9%-11.5%; P = .04), with corresponding increases in CD4+ Foxp3+ regulatory T cells (0.19%-1.12%; P = .001).
    Hookworms in the form of Necator americanus promoted tolerance and stabilized, or improved, all tested measures of gluten toxicity in volunteers with celiac disease. So, after being voluntarily infected with 20 hookworms, these celiac disease volunteers were able to eat increasingly large amounts of gluten with none of the usual changes or adverse symptoms.
    Could hookworm treatments represent the future of treatment for celiac disease, and maybe other inflammatory conditions? Clearly, further tests are needed to determine exactly how safe it is for celiac patients receiving this treatment to eat gluten. So far, however, the future looks bright.
    What do you think? If swallowing a small dose of hookworms would eliminate your adverse reactions, and allow you to safely eat gluten, would you do it?
    The radio program Radiolab has an interesting segment on hookworm, which you can stream here: Radiolab
    Source:
    Journal of Allergy and Clinical Immunology. DOI: http://dx.doi.org/10.1016/j.jaci.2014.07.022

  • Recent Articles

    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

    Jefferson Adams
    Celiac.com 06/13/2018 - There have been numerous reports that olmesartan, aka Benicar, seems to trigger sprue‐like enteropathy in many patients, but so far, studies have produced mixed results, and there really hasn’t been a rigorous study of the issue. A team of researchers recently set out to assess whether olmesartan is associated with a higher rate of enteropathy compared with other angiotensin II receptor blockers (ARBs).
    The research team included Y.‐H. Dong; Y. Jin; TN Tsacogianis; M He; PH Hsieh; and JJ Gagne. They are variously affiliated with the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School in Boston, MA, USA; the Faculty of Pharmacy, School of Pharmaceutical Science at National Yang‐Ming University in Taipei, Taiwan; and the Department of Hepato‐Gastroenterology, Chi Mei Medical Center in Tainan, Taiwan.
    To get solid data on the issue, the team conducted a cohort study among ARB initiators in 5 US claims databases covering numerous health insurers. They used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy‐related outcomes, including celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy. In all, they found nearly two million eligible patients. 
    They then assessed those patients and compared the results for olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. They found unadjusted incidence rates of 0.82, 1.41, 1.66 and 29.20 per 1,000 person‐years for celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy respectively. 
    After PS matching comparing olmesartan to other ARBs, hazard ratios were 1.21 (95% CI, 1.05‐1.40), 1.00 (95% CI, 0.88‐1.13), 1.22 (95% CI, 1.10‐1.36) and 1.04 (95% CI, 1.01‐1.07) for each outcome. Patients aged 65 years and older showed greater hazard ratios for celiac disease, as did patients receiving treatment for more than 1 year, and patients receiving higher cumulative olmesartan doses.
    This is the first comprehensive multi‐database study to document a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, though absolute rates were low for both groups.
    Source:
    Alimentary Pharmacology & Therapeutics