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    How Do We Tell Celiac Disease from Non-Celiac Gluten Sensitivity?


    Jefferson Adams

    Celiac.com 06/16/2014 - Differentiating between celiac disease and non-celiac gluten sensitivity (NCGS) is important for appropriate treatment, but is often challenging.


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    Photo: Wikimedia Commons--Igreja de CampahaA team of researchers recently set out to assess the best way to distinguish between celiac disease and non-gluten sensitivity. The research team included Toufic A Kabbani, Rohini R Vanga, Daniel A Leffler, Javier Villafuerte-Galvez, Kumar Pallav, Joshua Hansen, Rupa Mukherjee, Melinda Dennis and Ciaran P Kelly.

    For their study, the team reviewed records for 238 patients who were assessed for symptoms responsive to gluten restriction without having celiac disease ruled in or out. For each patient, clinicians noted the demographic information, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of celiac disease.

    They define NCGS as symptoms responsive to a gluten-free diet, together with negative celiac blood tests and negative duodenal biopsies while on a gluten-containing diet, or negative human leukocyte antigen (HLA) DQ2/DQ8 testing. Of the 238 patients in the study, 101 had celiac disease, 125 had NCGS, 9 had non-celiac enteropathy, and 3 remained undetermined. Nearly 70% of celiac disease subjects suffered symptoms of malabsorption compared with just under 25% of the NCGS subjects (P<0.0001).

    In addition, the patients with celiac disease were far more likely to have a family history of celiac disease (P=0.004), personal history of autoimmune diseases (P=0.002), or nutrient deficiencies (P<0.0001).

    The positive likelihood ratio for celiac disease diagnosis of a >2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to a gluten-free diet was 130 (confidence interval (CI): 18.5–918.3).

    The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5–16.9).

    When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and celiac disease risk factors (personal history of autoimmune diseases and family history of celiac disease), the positive likelihood ratio for NCGS increased to 80.9.

    Based on their findings, the team developed a diagnostic algorithm to distinguish celiac disease from NCGS.

    People with negative celiac blood tests (IgA tTG or IgA/IgG DGP, who are eating a regular gluten-containing diet, are unlikely to have celiac disease.

    Those with negative serology who show no clinical signs of malabsorption, and show no celiac disease risk factors, are highly likely to have NCGS and may not require further testing. Those with positive blood tests should undergo HLA typing to determine the need for biopsy.

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    Interesting article although the opening paragraph is puzzling. All that I have seen indicates that the treatment for celiac disease and NCGS is the same, i.e., a gluten free diet.

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Jefferson Adams
    Celiac.com 03/30/2011 - A team of medical researchers set out to compare gut permeability and mucosal immune gene expression in celiac disease and gluten sensitivity.
    The research team included Anna Sapone, Karen M Lammers, Vincenzo Casolaro, Marcella Cammarota, Maria T Giuliano, Mario De Rosa, Rosita Stefanile, Giuseppe Mazzarella, Carlo Tolone, Maria I Russo, Pasquale Esposito, Franca Ferraraccio, Maria Carteni, Gabriele Riegler, Laura de Magistris  and Alessio Fasano.
    People with celiac disease suffer an adverse autoimmune reaction when they consume gluten. People with gluten-sensitivity cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in celiac disease.
    However, for people with gluten intolerance, the overall clinical picture is usually less severe, and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities.
    By examining and comparing mucosal expression of genes associated with intestinal barrier function, along with innate and adaptive immunity the team sought to better understand the similarities and differences between celiac disease and gluten sensitivity.
    For their study, the team enrolled a group of subjects with celiac disease, a group with gluten sensitivity, and a control group of healthy, gluten-tolerant individuals.
    They assessed intestinal permeability using a lactulose and mannitol probe, and collected mucosal biopsy specimens to study the expression of genes involved in barrier function and immunity.
    They found that gluten sensitivity, unlike celiac disease, is not associated with increased intestinal permeability.
    In fact, subjects with gluten sensitivity showed significantly reduced intestinal permeability compared with controls (P = 0.0308). This was accompanied with significantly increased expression of claudin (CLDN) 4 (P = 0.0286).
    Relative to controls, subjects with celiac disease expressed higher levels of adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572), while those with gluten sensitivity showed no higher levels.
    Subjects with gluten intolerance showed increased expression of the innate immunity marker Toll-like receptor (TLR) 2, but subjects with celiac disease showed no such increase (P = 0.0295).
    Finally, subjects with gluten intolerance showed significantly reduced expression of the T-regulatory cell marker FOXP3 relative to controls (P = 0.0325) and celiac subjects (P = 0.0293).
    This study supports the existence of gluten sensitivity and celiac disease as two clinically different gluten-associated disorders.
    The study also supports the characterization of gluten sensitivity as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.
    Source:

    BMC Medicine 2011, 9:23 doi:10.1186/1741-7015-9-2

    Jefferson Adams
    Celiac.com 05/14/2012 - Should gluten sensitivity be thought of as “celiac light,” as just one of the milder manifestations within the wider spectrum of celiac disease? Some doctors and researchers think so.
    Over the past several years, there has been increasing discussion concerning gluten sensitivity as a possible cause of irritable bowel syndrome (IBS) symptoms in patients for whom celiac disease has been excluded. 
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    In a recent letter to the editors of the American Journal of Gastroenterology, doctors Courtney C. Ferch and William D. Chey of the Division of Gastroenterology at the University of Michigan Health System in Ann Arbor, Michigan, comment at length on the latest findings regarding Irritable Bowel Syndrome and gluten sensitivity without celiac disease.
    Ferch and Chey note that gluten sensitivity is one of the most rapidly growing sectors in the food industry, with gluten-free products accounting for $1.31 billion in U.S. sales alone in 2011. Those sales are expected to exceed $1.6 billion by 2015.
    Major food manufacturers such as General Mills and Betty Crocker, along with popular restaurant chains like PF Chang's and Subway are busy introducing new gluten-free options, or retooling original products into gluten-free versions.
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    Unlike celiac disease, there are no accepted biomarkers for gluten-sensitivity. Doctors diagnose the condition mainly by looking at the connection between eating gluten and the presence adverse symptoms.
    Numerous studies on gluten sensitivity suffer have included small sample size, a lack of adequate controls, a lack of blinding, and the use of non-validated outcome measures. Even with these limitations, Ferch and Chey say there are several studies worthy of further consideration.
    One of the studies discussed in the Ferch and Chey was a double-blind, placebo-controlled, dietary re-challenge trial performed by Biesiekierski et al. The study sought to better understand the role of gluten ingestion in the development of gastrointestinal (GI) and non-GI symptoms in patients diagnosed with IBS.
    The Biesiekierski study included a sample of 34 patients diagnosed with IBS by the Rome III criteria who had experienced symptom improvement with a gluten-free diet for 6 weeks before study enrollment. Celiac disease had been excluded in all study participants by either a negative HLADQ2/HLA-DQ8 haplotype or a normal duodenal biopsy. The study excluded patients with conditions such as cirrhosis, inflammatory bowel disease, non-steroidal anti-inflammatory drug ingestion, or excessive alcohol.
    Over a six week double-blind randomization phase, study participants followed either a gluten-free or gluten-containing diet that was assigned at random. Nineteen of the 34 patients ate food containing 16 g of gluten per day. The other 15 patients ate gluten-free bread and mufï¬ns. Gluten used in the study was free of fermentable oligo-, di-, monosaccharides and polyols, and its protein distribution included 2.3% nongluten, 45.7% glutenin, and 52% gliadin.
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    The study team also assessed secondary outcomes including bloating, abdominal pain, satisfaction with stool consistency, nausea, and tiredness using a 100-mm visual analog scale.
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    Meanwhile, high-sensitivity C-reactive protein levels remained normal before and after the dietary intervention.
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    In their letter, Ferch and Chey also comment on several side issues.
    First, they note that a recent global meta-analyses of studies showed that patients with IBS symptoms had signiï¬cantly higher rates of celiac disease than controls. As such, they point out that the American College of Gastroenterology Task Force now recommends routine celiac blood screens for patients with diarrhea-predominant IBS and IBS with a mixed bowel pattern (grade 1B recommendation).
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    Although these results are certainly intriguing and hypothesis generating, they require validation in larger, randomized, controlled trials in other parts of the world.
    What is clear and important for providers to understand is that gluten sensitivity is here to stay and signiï¬cantly more likely for them to encounter in day-to-day practice than celiac disease.
    Read the full letter by Ferch and Chey at the website for the  American Journal of Gastroenterology.
    Source:
    Am J Gastroenterol 2011;106:508 –514

    Jefferson Adams
    Celiac.com 06/13/2012 - In general, doctors and researchers know a good deal about how celiac disease works, and they are finding out more all the time. However, they know very little about non-celiac gluten sensitivity (NCGS).
    In an effort to learn more about non-celiac gluten sensitivity, a team of researchers recently carried out a study to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals, and to compare the results with celiac disease patients and healthy control subjects. They also compared the response to gluten challenge between patients with non-celiac gluten sensitivity and those with celiac disease.
    The research team included M. Brottveit, P.O. Vandvik, S. Wojniusz, A. Løvik, K.E. Lundin, and B. Boye, of the Department of Gastroenterology at Oslo University Hospital, Ullevål in Oslo, Norway.
    In all, the team looked at 22 patients with celiac disease and 31 HLA-DQ2+ NCGS patients without celiac disease. All patients were following a gluten-free diet.
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    The team then had both patients and healthy control subjects complete questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life.
    Interestingly, patients with non-celiac gluten sensitivity reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after the gluten challenge than patients with celiac disease. The increase in symptoms in non-celiac gluten sensitivity patients was not related to personality.
    However, the two groups both reported similar responses regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. Responses for both groups were about the same as for healthy controls.
    The results showed that patients with non-celiac gluten sensitivity did not show any tendencies toward general somatization, as both celiac disease patients and those with non-celiac gluten sensitivity showed low somatization levels.
    Source:
    Scand J Gastroenterol. 2012 Apr 23.

    Jefferson Adams
    Celiac.com 12/03/2012 - Gluten sensitivity has recently been added to the spectrum of gluten-related disorders, but precise diagnostic markers do not yet exist. A research team recently set out to understand the blood test pattern of gluten sensitivity, and to compare it with the blood test pattern seen in celiac disease.
    The researchers included U. Volta, F. Tovoli, R. Cicola, C. Parisi, A. Fabbri, M. Piscaglia, E. Fiorini, G. Caio, of the Department of Clinical Medicine at University of Bologna's St. Orsola-Malpighi Hospital in Bologna, Italy.
    For their study, the researchers looked at blood samples from 78 patients with gluten-sensitivity and 80 patients with celiac disease. They assessed levels of immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA).
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    Only 1 of the 78 patients with gluten-sensitivity tested positive for IgG DGP-AGA, which was found in nearly 90% of patients with celiac disease.
    All patients with gluten-sensitivity tested negative for IgA tTGA and IgA EmA, while 98.7% of patients with celiac disease tested positive for IgA tTGA, and 95% were positive for IgA EmA.
    Patients with gluten-sensitivity presented a variety of intestinal and extra-intestinal symptoms, including abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia. Small intestinal mucosa for these patients was either normal or only mildly abnormal.
    The data from these blood tests show that more than half of patients with gluten sensitivity will test positive for IgG AGA, and a small number will test positive for IgA AGA, but none will show positive results for EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.
    Source:
    J Clin Gastroenterol. 2012 Sep;46(8):680-5.

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    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.
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    The research was funded by the National Institutes of Health.
    Read more at: Sciencedaily.com

    Jefferson Adams
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    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.