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Persistent Anti-Borrelia IgM Antibodies without Lyme Borreliosis in the Clinical and Immunological Context.
Markowicz, M, Reiter, M, Gamper, J, Stanek, G, Stockinger, H
Microbiology spectrum. 2021;9(3):e0102021
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Borrelia burgdorferi (BD) specific Immunoglobulin (Ig) antibodies are a diagnostic key for infection and Lyme’s disease. Generally, IgM is reflective of recent infection and converts to IgG after several weeks during disease progression or inadequate treatment. Yet, in the early phase of infection, not all cases present with antibodies and at the same time, both IgM and IgG can persist in healthy people after tick exposure or treatment. This study sought to investigate further the common phenomenon of persistence of IgM, regardless of symptomatic BD infection. The study examined the serum of 59 predominantly female patients, that showed persistent IgM antibodies in the absence of IgG. The majority of subjects experienced non-specific symptoms, and half of them had a history of antibiotic treatment, yet IgM persisted. The observation went on for >6 months, thus excluding the likelihood of any acute infection. The results showed that in people with lower IgM count a greater improvement of non-specific symptoms was observed as opposed to those with higher IgM count. Furthermore, the assay identified multiple cross-reactivity patterns from other plants, bacteria and human tissue to the antigen-binding receptor OspC typically used for BD testing. The authors postulate that the phenomena of IgM persistence potentially originates from a previous infection with BD, but may be maintained in some individuals by continuous stimulation with cross-reactive antigens from other sources. This is important knowledge for the interpretation and improvement of testing for BD. Of clinical interest here is that IgM persistence, beyond the acute phase, maybe no longer be reflective of the original BD infection. And in such cases, non-specific symptoms may be sustained by other triggers such as foods, other microorganisms and autoimmunity.
Abstract
The aim of the study was to investigate the etiology of persistent IgM antibodies against Borrelia burgdorferi sensu lato (sl) and to analyze their association with nonspecific symptoms. The study group comprised individuals with persistent IgM antibodies in the absence of IgG. The relation between ELISA values and time elapsed since past erythema migrans (EM) was analyzed. Previous antibiotic treatments were assessed. The association between persistent IgM and nonspecific symptoms was evaluated statistically. Specificity of IgM antibodies for outer surface protein C (OspC) of B. burgdorferi sl was examined by immunoblotting. Further, we investigated the cross-reactivity with Borrelia-unrelated proteins. Fifty-nine patients (46 women; 78%) were included in the study group. The mean IgM-ELISA values did not change significantly during follow-up (median 6.2 months). The mean ELISA value in the study group was dependent on time elapsed since past EM. Nonspecific symptoms improved significantly more often in patients with lower IgM ELISA results. Persistent IgM antibodies were specific for the C-terminal PKKP motif of OspC. Cross-reacting C-terminal PKKP antigens from both human and prokaryotic origins were identified. We demonstrate that the C-terminal PKKP motif plays a main role for the reactivity of persistent Borrelia IgM toward OspC. However, cross-reactivity to other eukaryotic and/or prokaryotic antigens may hamper the specificity of OspC in the serological diagnosis of Lyme borreliosis. Lack of improvement of nonspecific symptoms was associated with higher IgM ELISA values. IMPORTANCE The reactivity of human IgM with the outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is frequently used to detect Borrelia specific IgM in commercial immunoassays, and such antibodies usually occur in the early phase of the infection. We identified a group of individuals with persistent Borrelia IgM without symptoms of Lyme borreliosis. We used their sera to demonstrate that the C-terminal epitope of OspC binds the IgM. Strikingly, we found that the same epitope occurs also in certain proteins of human and environmental origin; the latter include other bacteria and food plants. Our experimental data show that these Borrelia-unrelated proteins cross-react with the OpsC-specific IgM. This knowledge is important for the development of serologic assays for Lyme borreliosis and provides a cross-reactive explanation for the persistence of Borrelia-IgM.
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Another Chicken and Egg Story: Systematic Review on Lichen Planus as a Precursor for Celiac Disease in Adult Population.
Khan, S, Patel, S, M, S, Hamid, P
Cureus. 2020;12(8):e9526
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Lichen planus is a rare, chronic, inflammatory skin condition affecting the mucous membranes. It is immunological, sometimes regarded as autoimmune, and associated with some autoimmune disorders and infectious diseases. The presence of an autoimmune disorder increases the likelihood of the co-occurrence or development of other autoimmune conditions, and such is the case in Coeliac disease (CD). CD is an autoimmune condition leading to damage to the gastrointestinal tissue. CD can remain undetected in many patients, yet skin manifestations can occur long before or together with gastrointestinal damage. Hence the authors of this study were interested in how CD and Lichen planus related to each other and whether Lichen planus can be an early marker for CD. For this 2389 studies were assessed, with the inclusion of nine in the final assessment - a mix of case reports, observational studies, and systematic and traditional reviews. The authors could identify a correlation between lichen planus and CD but could not establish causation or a clear relationship between the two conditions. In conclusion, the authors advocated for more studies on larger population groups. Of clinical interest is the author's suggestion that in LP patients with signs of mouth ulcers and skin eruptions testing for CD and a gluten-free diet is warranted and could help manage disease progression.
Abstract
Celiac disease is receiving much attention due to the gluten-free diet trend. Many health-conscious individuals practice a gluten-free diet, even if they do not have celiac disease. As it is an autoimmune disorder, it is associated with many other autoimmune diseases. We were interested in one skin condition, another autoimmune disorder lichen planus as a correlative factor for celiac disease. The following systematic review may give some clues. We searched online resources including PubMed, PubMed Central, Cochrane library, and Google scholar for systematic reviews, traditional reviews, randomized controlled trials, and meta-analysis on celiac disease and lichen planus. We included human studies published in peer-reviewed journals in the English language. After reviewing 2389 initial results of our search, we excluded 1250 duplicates, 1108 abstracts, 42 irrelevant articles. We assessed the remaining 26 articles for their quality using various quality assessment tools. After the quality assessment, we included nine final articles in our systematic review. Out of these nine studies, there were four systematic reviews, one traditional review, two case reports, and two observational studies. Only two articles had exclusively studied the specific association between celiac and lichen planus. The remaining studies included data that gave an overall association between other skin manifestations of celiac disease. From our study, we could not establish the relationship between celiac disease and lichen planus. We need more case-control studies and clinical trials with a larger population to get conclusive data. From current data, we can conclude that both immunological processes correlate but there is no causation. There is also a need for clinical trials to explore the exacerbation of lichen planus due to celiac disease.
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The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia.
Dzikowski, M, Juchnowicz, D, Dzikowska, I, Rog, J, Próchnicki, M, Kozioł, M, Karakula-Juchnowicz, H
Journal of clinical medicine. 2020;9(11)
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Schizophrenia is a heterogeneous neuroimmune disorder with unknown mechanisms and aetiology. The goal of this clinical study was to compare and evaluate IgG and IgA sensitivity, inflammation, and gut integrity between 52 first episode Schizophrenia patients, 50 chronic Schizophrenia patients, and 60 healthy controls to explain whether there were any associations between these markers. Study results show that antigliadin IgG and IgA antibodies, as well as inflammatory markers such as hs-CRP and IL-6, were significantly higher in the first episodes of schizophrenia and chronic schizophrenia patients when compared to the healthy controls. Schizophrenia risk was 4-7% higher among those with elevated Antigliadin IgG and IgA antibody levels. In addition, smoking cigarettes has been shown to increase the risk of developing schizophrenia. Patients with chronic schizophrenia showed elevated levels of anti-Saccharomyces cerevisiae antibody and soluble CD14, indicating bacterial translocation and immune activation. To understand the mechanisms behind chronic Schizophrenia, which link inflammation, immune responses, and the gut-brain axis, further robust larger studies are necessary. The results of this study can be used by healthcare professionals to understand the relationship between intestinal permeability, inflammation, and food hypersensitivity.
Abstract
Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23-15.39) for AGA IgA and 3.08 (95% CI 1.19-7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.
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Exposure to Different Amounts of Dietary Gluten in Patients with Non-Celiac Gluten Sensitivity (NCGS): An Exploratory Study.
Roncoroni, L, Bascuñán, KA, Vecchi, M, Doneda, L, Bardella, MT, Lombardo, V, Scricciolo, A, Branchi, F, Elli, L
Nutrients. 2019;11(1)
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Non-coeliac gluten sensitivity (NCGS) is characterised by adverse gastrointestinal symptoms related to ingestion of gluten-containing foods and amelioration of symptoms when gluten is removed from the diet. It is currently unclear whether gluten sensitivity is a permanent condition. The aim of this exploratory study was to evaluate the effects of gluten re-introduction in 22 NCGS patients who have been on a strict gluten-free diet for three weeks. Working with a qualified nutritionist, participants began incrementally introducing gluten each week for three weeks. Gastrointestinal symptoms and quality of life were assessed at baseline and post-intervention. When adverse symptomology was reported, participants returned to the gluten-level before symptoms started. This study found mixed results with gluten reintroduction. Of the 22 participants, 8 were able to return to a normal gluten-containing diet, and the remaining participants had differing levels of tolerance for gluten consumption. Based on these results, the authors conclude further controlled studies are required to assess the clinical response of reintroducing dietary gluten in patients with NCGS.
Abstract
It is unclear whether patients with non-celiac gluten sensitivity (NCGS) can tolerate gluten. We have evaluated the changes of both gastrointestinal symptoms and quality of life for NCGS patients after the re-introduction of dietary gluten. Twenty-two NCGS patients reporting functional gastroenterological symptoms and on gluten-free diet (GFD) for the previous three weeks were exposed to incremental gluten-containing diets. Three groups were compared at baseline (immediately after 3-weeks on GFD) and immediately after the return of symptomatology: (i) a group tolerating a low-gluten diet (3.5 g gluten/day, week 1, n = 8), (ii) a group tolerating a mid-gluten diet (8 g gluten/day, week 2, n = 6), and (iii) a group tolerating a high-gluten diet (13 g gluten/day, week 3, n = 8). Their gastrointestinal symptoms and quality of life were assessed at baseline and post-intervention. The most common symptoms were: constipation (46%), abdominal pain (50%) and dyspepsia (38%). A decrease in several short form health survey (SF-36) sub-scores (all p < 0.03) after gluten re-introduction was only observed in the group tolerating the low-gluten diet; the same group showed a lower post-intervention role-emotional SF-36 score (p = 0.01). Most gastrointestinal symptoms remained similar after gluten re-introduction. However, a decrease in the general perception of well-being was only found after gluten re-introduction in the group tolerating a low-gluten diet (p = 0.01); the same was true when comparing the post-intervention general well-being perception among the three groups (p = 0.050). In conclusion, dissimilar responses from patients with NCGS were observed after the re-introduction of gluten, with gluten at a low dosage affecting the quality of life and general well-being of a group of patients, whereas others tolerate even higher doses of dietary gluten.
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A Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients With Nonalcoholic Fatty Liver Disease (NAFLD): A Randomized Clinical Trial.
Dinu, M, Whittaker, A, Pagliai, G, Giangrandi, I, Colombini, B, Gori, AM, Fiorillo, C, Becatti, M, Casini, A, Benedettelli, S, et al
Journal of the American College of Nutrition. 2018;37(6):508-514
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Non-alcoholic fatty liver disease (NAFLD) is prevalent, however early intervention with lifestyle modifications such as weight loss, dietary therapy and physical activity may reverse it. Previous studies have shown that the Mediterranean diet, which includes a large proportion of grains, may reduce NAFLD. However no prior studies have assessed grains in isolation on these individuals. This randomised double blind parallel arm study aimed to assess the effects of a replacement diet with ancient khorasan wheat products on patients with NAFLD. 40 people with mild- moderate NAFLD were assigned to either khorasan wheat diet or a modern wheat grain diet for three months. This comparatively small study found that a khorasan wheat based diet improved liver function and inflammation. However regardless of the diet, measures of oxidative stress, which assesses the imbalance of free radicals and antioxidants in the body, was significantly reduced and some individuals were shown to regress from moderate to mild NAFLD. Nutrition practitioners who have clients with mild-moderate NAFLD may recommend a khorasan wheat based diet in the short term to improve biochemical and inflammatory markers and to potentially reverse disease development.
Abstract
OBJECTIVE KAMUT khorasan is an ancient grain with widely acclaimed health benefits. The aim of this study was to investigate the effects of a replacement diet with ancient khorasan wheat products in patients with NAFLD, in comparison to a similar replacement diet with control products made from organic semi-whole-grain modern wheat. METHODS Forty NAFLD patients (12 M/28 F; age 55.2 ± 10.4 years) with mild to moderate liver steatosis were included. The experimental design was a randomized, double-blind, parallel-arm study with 20 participants assigned to consume either KAMUT khorasan or control wheat products (pasta, bread, crackers, biscuits) over a 3-month period. Anthropometric measurements, blood analyses, and ultrasonography examination were performed at both the beginning and end of each dietary intervention. RESULTS After the implementation of a general linear model for repeated measurements adjusted for baseline demographic details, risk factors, and medication, alanine aminotransferase (ALT) was significantly reduced by 12%, aspartate aminotransferase (AST) by 14%, alkaline phosphatase (ALP) by 8%, and cholesterol by 6% only in the khorasan group (p < 0.05 for all). Similarly, significant reductions in circulating proinflammatory tumor necrosis factor-alpha by 50%, interleukin l-receptor antagonist-alpha by 37%, interleukin-8 by 24%, and interferon gamma by 24% were evident only in participants who consumed the khorasan products (p < 0.05 for all). Finally, significant improvements in the liver steatosis grading, Doppler perfusion index values, and reactive oxygen species (ROS) production were evident after consumption of both the khorasan and control products. CONCLUSIONS This study suggests that a short-term replacement diet with ancient KAMUT khorasan products is most effective in reducing metabolic risk factors and ameliorating the liver profile in patients with NAFLD.
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Is perceived intolerance to milk and wheat associated with the corresponding IgG and IgA food antibodies? A cross sectional study in subjects with morbid obesity and gastrointestinal symptoms.
Kvehaugen, AS, Tveiten, D, Farup, PG
BMC gastroenterology. 2018;18(1):22
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Dairy and gluten are the most common triggers of irritable bowel syndrome (IBS) in the general population. Food intolerance is generally detected by IgG antibodies, but the test is controversial. In this cross-sectional study, 97 obese subjects (82.4% women) were included, of which 72.1% had gastrointestinal symptoms, 35.7% had IBS, 31.4% had symptoms of milk intolerance, 28.6% had symptoms of wheat intolerance, and 15.7% had symptoms of intolerance to both milk and wheat. The study examined the association between IgA and IgG antibodies corresponding to milk and wheat in subjects with and without gastrointestinal issues and with and without perceptions of food sensitivity. The results of this study found no association between s-IgG and s-IgA antibodies and perceived food intolerances to milk and wheat among morbidly obese subjects. Although IgA against gliadin correlated with increased levels of zonulin, a marker of intestinal permeability, tight-junctional gut permeability inversely correlated with wheat intolerance. Furthermore, the study results revealed a significant correlation between hypothyroidism and IgG against wheat and a marginal correlation between hypothyroidism and IgG against gluten. Further robust research is needed to confirm these findings. Healthcare professionals can use the results of this study to understand the current developments and the controversy surrounding food intolerance testing.
Abstract
BACKGROUND Serum IgG and IgA food antibodies have been used for dietary advice to subjects with gastrointestinal symptoms and perceived food intolerance, but the role of these antibodies in mediating intolerance is controversial. The present study investigated associations between perceived gastrointestinal intolerance to milk-or wheat and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity. METHODS Subjects with morbid obesity (BMI ≥ 40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were included. Irritable Bowel Syndrome (IBS) was diagnosed based on the Rome III criteria. Severity of specific gastrointestinal symptoms were measured with the Gastrointestinal Symptom Rating Scale (GSRS)-IBS. S-IgG against cow's milk, cheese, wheat and gluten, and s-IgA against casein and gliadin were measured. RESULTS Ninety-seven subjects (80 females) with mean age 45 (SD 8.4) years were included, 70 had gastrointestinal complaints, 25 had IBS, and 22 and 20 reported milk- and wheat- intolerance respectively. There were no significant differences in serum concentrations or proportions of subjects above defined cut-off values for the antibodies between subjects with and without gastrointestinal complaints. In the group with gastrointestinal complaints, no significant differences were found between subjects with and without perceived food intolerance. Except for a significant correlation between IgG against cheese and GSRS-diarrhea (Rho: -0.25, P = 0.04), no significant correlations were found between the antibodies and type or degree of gastrointestinal symptoms, including IBS. CONCLUSIONS The study showed no associations between perceived milk or wheat intolerance and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity.
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High Frequency of Extractable Nuclear Autoantibodies in Wheat-Related Disorders.
Yang, Y, Krishna, K, Deshpande, P, Ranganathan, V, Jayaraman, V, Wang, T, Bei, K, Krishnamurthy, H
Biomarker insights. 2018;13:1177271918782893
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Celiac disease and nonceliac wheat sensitivity (NCWS) are both disorders, which are characterised by both stomach and non-stomach related symptoms, following the ingestion of wheat. Celiac disease has been associated with diseases where the body’s immune system attacks its own cells, otherwise known as autoimmunity, however there is little research regarding this and how NCWS may be involved. This study of 713 individuals aimed to determine the presence of a blood marker, which indicates autoimmunity, amongst individuals with celiac disease and NCWS. The results showed that markers of autoimmunity were present in patients with wheat-related disorders. It was concluded that those with wheat-related disorders do display markers of autoimmunity. This study could be used by healthcare professionals to understand that testing individuals with wheat-related disorders for autoimmune diseases, may give a false positive due to the presence of the wheat-related disorder expressing markers of autoimmunity. To negate this effect, differentiation between the markers displayed in autoimmune diseases may be required to reach a definitive diagnosis.
Abstract
BACKGROUND AND AIMS There has been broad interest to explore the presence of autoimmunity among wheat-sensitive individuals, but neither the pathogenesis nor the relevance has been established. In this study, we evaluated the frequencies and levels of autoantibodies, which are important biomarkers of autoimmunity, in subjects with wheat-related disorders and controls. Anti-nuclear antibodies (ANA) and the specific ones against extractable nuclear antigens (ENA) were investigated. METHODS A total of 713 subjects who showed symptoms related to wheat ingestion were addressed to Vibrant America Clinical Laboratory from December 2015 to November 2017. Serum samples were collected from all subjects and tested with a wheat protein antibody panel (IgG and IgA to 18 proteins at the peptide level) and an autoantibody panel (ANA by immunofluorescence analysis and 10 ENA antibodies). Retrospective analysis was completed using de-identified clinical data and test results. RESULTS In the retrospective analysis, 38 (5%) were seropositive in a Celiac Disease panel, 491 (83%) were seropositive in a wheat protein antibody panel "Wheat Zoomer," and 84 (12%) were seronegative in both panels. Anti-nuclear antibodies were detected in similar portions of the celiac disease subjects (13%), the Wheat Zoomer-positive subjects (12%), and seronegative controls (15%), which is also very close to the reported occurrence of ANA positivity (15%) in the healthy population. The prevalence of anti-ENA was reported to be less than 2% in the general population; however, our study found it to be much higher in the celiac disease subjects (29%) and the wheat-sensitive subjects (27%), compared with a smaller proportion of seronegative controls (19%). The prevalence of anti-histone was especially prominent among the celiac disease subjects (73%) and the Wheat Zoomer-positive subjects (60%). CONCLUSIONS High proportions of wheat-related disease subjects carry ENA antibodies that are important specific biomarkers of autoimmunity.
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Integrated Evaluation of the Potential Health Benefits of Einkorn-Based Breads.
Antognoni, F, Mandrioli, R, Bordoni, A, Di Nunzio, M, Viadel, B, Gallego, E, Villalba, MP, Tomás-Cobos, L, Taneyo Saa, DL, Gianotti, A
Nutrients. 2017;9(11)
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While health benefits of whole grains has been long established, recent findings suggest ancient grains may provide additional cardiovascular and anti-inflammatory benefits. Einkorn is an ancient crop that has a favourable biochemical makeup however very little research exists on its properties. The aim of this study was to evaluate the nutritional characteristics and health benefits of eikorn-based bread compared to wheat-based breads. Both types of grains were subject to either conventional fermentation with baker’s yeast or sourdough fermentation with lactic acid. Breads were digested in-vitro using the Dynamic Gastrointestinal Digestor, a controlled system that simulates the in vivo digestion process. Bread content was characterised before and after digestion, and the product of their digestion was used to evaluate anti-inflammatory effects. The primary finding of this study was a significantly higher carotenoid level in einkorn compared to modern wheat. Additionally, the use of sourdough fermentation aided to preserve these carotenoids, thus improving the availability and accessibility of nutrient absorption in the final product. Based on this study, the authors conclude einkorn is a good candidate to produce bakery products with enhanced nutritional properties.
Abstract
Nowadays the high nutritional value of whole grains is recognized, and there is an increasing interest in the ancient varieties for producing wholegrain food products with enhanced nutritional characteristics. Among ancient crops, einkorn could represent a valid alternative. In this work, einkorn flours were analyzed for their content in carotenoids and in free and bound phenolic acids, and compared to wheat flours. The most promising flours were used to produce conventional and sourdough fermented breads. Breads were in vitro digested, and characterized before and after digestion. The four breads having the best characteristics were selected, and the product of their digestion was used to evaluate their anti-inflammatory effect using Caco-2 cells. Our results confirm the higher carotenoid levels in einkorn than in modern wheats, and the effectiveness of sourdough fermentation in maintaining these levels, despite the longer exposure to atmospheric oxygen. Moreover, in cultured cells einkorn bread evidenced an anti-inflammatory effect, although masked by the effect of digestive fluid. This study represents the first integrated evaluation of the potential health benefit of einkorn-based bakery products compared to wheat-based ones, and contributes to our knowledge of ancient grains.
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Reintroduction of gluten following flour transamidation in adult celiac patients: a randomized, controlled clinical study.
Mazzarella, G, Salvati, VM, Iaquinto, G, Stefanile, R, Capobianco, F, Luongo, D, Bergamo, P, Maurano, F, Giardullo, N, Malamisura, B, et al
Clinical & developmental immunology. 2012;2012:329150
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A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying new strategies. Chemically altering the protein in wheat flour (transamidation of gliadin) reduces the reaction experienced in vitro in intestinal cells of CD patients. This randomized single blinded, controlled 90-day trial in 47 CD patients examines the safety of transamidated wheat flour compared to control. 35 patients received 50g a day of transamidated flour bread and 12 received 3.7g of non-transamidated flour bread. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse whereas intestinal permeability was mainly altered in the control group. On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no change to the autoantibody found in CD (Ttg) and other markers of CD. This study demonstrated that a protracted intake of gluten from chemically treated wheat flour was associated with a reduced number of relapses in challenged patients. Nevertheless, the enzyme reaction did not eradicate gluten activity in all CD patients examined. Whether an upgrade of the transamidation reaction might be instrumental in blocking other immune components involved in the mucosal lesion is under investigation.
Abstract
A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12) or transamidated (35) flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse (P = 0.04) whereas intestinal permeability was mainly altered in the control group (50% versus 20%, P = 0.06). On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA (P = 0.63), Marsh-Oberhuber grading (P = 0.08), or intestinal IFN-γ mRNA (P > 0.05). Creatinine clearance did not vary after 90 days of treatment (P = 0.46). In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function.