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    Clinical and Phenotypical Assessment of Seronegative Villous Atrophy


    Jefferson Adams


    • Most patients with SNVA, especially non-white patients, do not have celiac disease.


    Image Caption: Photo: US Army Materiel Command

    Celiac.com 11/10/2016 - Seronegative villous atrophy (SNVA) is commonly attributed to celiac disease. However, celiac is not the sole cause of SNVA.


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    Recent reports have pointed to a connection with angiotensin-2-receptor-blockers (A2RBs), but data on such cases of SNVA was limited to centers dealing with complex case referrals, and not SNVA in general.

    A team of researchers recently completed a clinical and phenotypical assessment of SNVA over a 15-year period. The research team included I Aziz, MF Peerally, JH Barnes, V Kandasamy, JC Whiteley, D Partridge, P Vergani, SS Cross, PH Green, DS Sanders. They are variously affiliated with the Academic Department of Gastroenterology, the Department of Microbiology, the Department of Histopathology at the Royal Hallamshire Hospital in Sheffield, UK, and with the Department of Medicine, Columbia University College of Physicians and Surgeons, Celiac Disease Center, New York, New York, USA.

    Over a 15-year period (2000-2015) the team assessed 200 adult patients with SNVA. Patients were diagnosed with either seronegative celiac disease (SNCD) or seronegative non-celiac disease (SN-non-celiac disease). The team then made baseline comparisons between the groups, with 343 seropositive celiac disease patients serving as controls.

    Of the 200 SNVA cases, SNCD represented 31% (n=62) and SN-non-celiac disease 69% (n=138). The human leucocyte antigen (HLA)-DQ2 and/or DQ8 genotype was present in 61%, with a 51% positive predictive value for SNCD. The breakdown of identifiable causes in the SN-non-celiac disease group comprised infections (27%), inflammatory/immune-mediated disorders (17.5%) and drugs (6.5%; two cases related to A2RBs).

    However, the researchers found no obvious cause in 18%, while duodenal histology spontaneously normalized in 72% of SNVA patients, while those patients were consuming a gluten-enriched diet.

    Following multivariable logistic regression analysis, the only independent factor associated with SN-non-celiac disease was non-white ethnicity (OR 10.8, 95% CI 2.2 to 52.8); in fact, 66% of non-white patients showed GI infections. On immuno-histochemistry all groups stained positive for CD8-T-cytotoxic intraepithelial lymphocytes. However, additional CD4-T helper intraepithelial lymphocytes were occasionally seen in SN-non-celiac disease mimicking the changes associated with refractory celiac disease.

    Most patients with SNVA, especially non-white patients, do not have celiac disease. Furthermore, a subgroup of patients with no obvious cause for their SNVA will show spontaneous histological resolution while consuming gluten. Based on these findings, the researchers encourage doctors to investigate patient condition before prescribing 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 06/06/2014 - Celiac disease guidelines suggest that some patients with high anti-tTG ab levels might be diagnosed without biopsy.
    A team of Indian researchers recently reviewed their celiac disease database to determine if anti-tissue transglutaminase (tTG) antibody (ab) titers correlate with severity of villous abnormalities in Indian patients, and to find out a cutoff value of anti-tTG ab fold-rise that might best predict celiac disease. The researchers included P. Singh, L. Kurray, A. Agnihotri, P. Das, A.K. Verma, V. Sreenivas, S. Datta Gupta, and G.K. Makharia. The are affiliated with the Departments of Gastroenterology and Human Nutrition, Pathology, and Biostatistics at the All India Institute of Medical Sciences in New Delhi, India.
    The team reviewed data on 366 anti-tTG ab-positive individuals who received duodenal biopsies. The team conducted anti-tTG ab screens before patients began a gluten-free diet, and they expressed anti-tTG ab results in terms of fold-rise by calculating ratio of observed values with cutoff value. Celiac disease was diagnosed only in patients with positive serology, villous atrophy greater than Marsh grade 2, and clear response to gluten-free diet.
    Average anti-tTG fold-rise in groups with Marsh grade ≤2 was 2.6 (±2.5), grade 3a was 4.0 (±3.9), 3b was 5.7 (±5.1), and 3c was 11.8 (±8.0). Overall positive likelihood ratio for diagnosing celiac disease was 15.4 and 27.4 at 12- and 14-fold-rise of anti-tTG ab titer, respectively.
    The positive predictive value of diagnosis of celiac disease was 100% when anti-tTG ab titer was 14-fold higher over the cutoff value. Fifty-seven (43.9%) patients with anti-tTG titer rise less than 2-fold also had celiac disease. Levels of anti-tTG rise directly with severity of villous abnormality. High anti-tTG ab titers indicate likely villous atrophy.
    Contrary to emerging wisdom, even patients with anti-tTG ab levels less than 2-times baseline should receive mucosal biopsies, because many patients with celiac disease have such low levels.
    Source:
     J Clin Gastroenterol. 2014 Feb 27.

    Jefferson Adams
    Celiac.com 11/04/2015 - A research team that conducted an analysis of the relationship between seronegative celiac disease and immunoglobulin deficiencies also conducted a literature search on the main medical databases, which revealed that seronegative celiac disease poses a diagnostic dilemma.
    The research team included F. Giorgio, M. Principi, G. Losurdo, D. Piscitelli, A. Iannone, M. Barone, A. Amoruso, E. Ierardi, and A. Di Leo. They are variously affiliated with the Section of Gastroenterology at University Hospital Policlinico, Department of Emergency and Organ Transplantation at University of Bari in Bari, Italy.
    They note that villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers in addressing seronegative celiac disease. They also note that immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of seronegative celiac disease patients may be useful.
    In the team's view, tTG-mRNA was similarly increased in seropositive celiac disease and suspected seronegative celiac disease, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders.
    An immune deregulation, severely lacking B-cell differentiatio, underlies the association of seronegative celiac disease with immunoglobulin deficiencies. Therefore, celiac disease may be linked to autoimmune disorders and immune deficits, known as common variable immunodeficiency (CVID)/IgA selective deficiency.
    CVID is a heterogeneous group of antibody dysfunction, whose association with celiac disease revealed only by a positive response to a gluten-free diet. The research team suggests a possible familial inheritance between celiac disease and CVID.
    Selective IgA deficiency, commonly associated with celiac disease, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare, with less than 300 documented cases, and is connected to celiac disease in 5% of cases.
    The team diagnosed seronegative celiac disease in a patient affected by sIgMD using the tTG-mRNA assay. One-year on a gluten-free diet restored IgM levels.
    This study data support a link between seronegative celiac disease and immunoglobulin deficiencies, and invites researchers to take a closer look at this connection.
    Source:
    Nutrients. 2015 Sep 8;7(9):7486-504. doi: 10.3390/nu7095350

    Jefferson Adams
    Celiac.com 01/13/2016 - Researchers are zeroing in on markers for gluten sensitivity in people who don't have celiac disease.
    So far, there's been scant proof of what causes gluten sensitivity in people who don't have celiac disease. It's been difficult to even pin down the existence of a condition that can be tested and diagnosed.
    The results of a recent study may change that. The study, from Giovanni Barbara and his team at the University of Bologna, Italy, suggests that inflammation in gluten-sensitive individuals may result from high levels of a molecule called zonulin.
    Zonulin has been linked to inflammation, and people with celiac disease have been shown to have high levels of zonulin when consuming wheat protein. Symptoms include abdominal pain, bloating, alternating diarrhea or constipation. And there can be other symptoms, including "brain fog," headache, fatigue and joint and muscle pain.
    Barbara's study found that zonulin levels in gluten-sensitive individuals almost matched those of celiacs.
    The researchers stress the preliminary nature of the results, but note that this information could lead to testing methods for detecting gluten sensitivity in people who don't have celiac disease.
    According to gastroenterologist Alessio Fasano of Massachusetts General Hospital in Boston, about 6 percent of the global population may be sensitive to gluten, so any breakthrough in identifying and testing for non-celiac gluten sensitivity could impact tens of millions of people worldwide.
    Stay tuned for more on zonulin and it's role in non-celiac gluten sensitivity. 
     Source:
    NPR.ORG

    Jefferson Adams
    Celiac.com 08/24/2016 - Although serological tests are useful for identifying celiac disease, it is well known that a small minority of celiacs are seronegative, and show no blood markers for celiac disease. A team of researchers wanted to define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy.
    The research team included U Volta, G Caio, E Boschetti, F Giancola, KJ Rhoden, E Ruggeri, P Paterini, and R De Giorgio. They are all affiliated with the Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy. They looked at clinical, histological and laboratory findings from 810 celiac disease diagnoses, and retrospectively characterized seronegative patients.
    Of the original 810 patients, they found fourteen patients who fulfilled diagnostic criteria for seronegative celiac disease, which were antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Their review showed that, compared to seropositive patients, seronegative celiac patients showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype, such as malabsorption, along with autoimmune disorders and severe villous atrophy.
    The most common diagnosis in the 31 cases with seronegative flat mucosa was celiac disease at 45%, along with Giardiasis at 20%, common variable immunodeficiency at 16%, and autoimmune enteropathy at 10%.
    Although rare, seronegative celiac disease is the most common cause of seronegative villous atrophy with a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders.
    Physicians treating seronegative villous atrophy should consider seronegative celiac disease as a possibility.
    Source:
    Dig Liver Dis. 2016 Jun 11. pii: S1590-8658(16)30460-1. doi: 10.1016/j.dld.2016.05.024.

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    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.
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    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

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    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.
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    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.
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    Purée all ingredients together in a blender.
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    Serve is a bowl with tortilla chips and guacamole.