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Concept: Coeliac disease

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Objective To examine the association of long term intake of gluten with the development of incident coronary heart disease.Design Prospective cohort study.Setting and participants 64 714 women in the Nurses' Health Study and 45 303 men in the Health Professionals Follow-up Study without a history of coronary heart disease who completed a 131 item semiquantitative food frequency questionnaire in 1986 that was updated every four years through 2010.Exposure Consumption of gluten, estimated from food frequency questionnaires.Main outcome measure Development of coronary heart disease (fatal or non-fatal myocardial infarction).Results During 26 years of follow-up encompassing 2 273 931 person years, 2431 women and 4098 men developed coronary heart disease. Compared with participants in the lowest fifth of gluten intake, who had a coronary heart disease incidence rate of 352 per 100 000 person years, those in the highest fifth had a rate of 277 events per 100 000 person years, leading to an unadjusted rate difference of 75 (95% confidence interval 51 to 98) fewer cases of coronary heart disease per 100 000 person years. After adjustment for known risk factors, participants in the highest fifth of estimated gluten intake had a multivariable hazard ratio for coronary heart disease of 0.95 (95% confidence interval 0.88 to 1.02; P for trend=0.29). After additional adjustment for intake of whole grains (leaving the remaining variance of gluten corresponding to refined grains), the multivariate hazard ratio was 1.00 (0.92 to 1.09; P for trend=0.77). In contrast, after additional adjustment for intake of refined grains (leaving the variance of gluten intake correlating with whole grain intake), estimated gluten consumption was associated with a lower risk of coronary heart disease (multivariate hazard ratio 0.85, 0.77 to 0.93; P for trend=0.002).Conclusion Long term dietary intake of gluten was not associated with risk of coronary heart disease. However, the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. The promotion of gluten-free diets among people without celiac disease should not be encouraged.

Concepts: Epidemiology, Medical statistics, Heart, Risk, Prevalence, Coeliac disease, Gluten-free diet, Whole grain

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Wheat gluten and related proteins can trigger an autoimmune enteropathy, known as coeliac disease, in people with genetic susceptibility. However, some individuals experience a range of symptoms in response to wheat ingestion, without the characteristic serological or histological evidence of coeliac disease. The aetiology and mechanism of these symptoms are unknown, and no biomarkers have been identified. We aimed to determine if sensitivity to wheat in the absence of coeliac disease is associated with systemic immune activation that may be linked to an enteropathy.

Concepts: Immune system, Wheat, Coeliac disease, Gluten, Gluten-free diet, Wheat allergy, Malabsorption, Gliadin

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BACKGROUND: Celiac disease is defined as a ‘chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Sweden has experienced an “epidemic” of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic. METHODS: A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child’s general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents. RESULTS: Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P<0.001). CONCLUSION: This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease. In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants for whom breastfeeding had been discontinued prior to gluten introduction. Regarding contribution to the Swedish celiac disease epidemic, which partly was attributed to concurrent changes in infant feeding, early infections probably made a minor contribution via the synergistic effect with gluten amount.

Concepts: Medicine, Infant, Epidemiology, Infectious disease, Nutrition, Infection, Transmission and infection of H5N1, Coeliac disease

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Celiac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency. However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin have never been explored in celiac disease.

Concepts: Immune system, Coagulation, Escherichia coli, Folic acid, Coeliac disease, Vitamin K, Malabsorption, Methylenetetrahydrofolate reductase

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Non-celiac gluten sensitivity is a syndrome characterized by gastrointestinal and extra-intestinal symptoms occurring in a few hours/days after gluten and/or other wheat protein ingestion and rapidly improving after exclusion of potential dietary triggers. There are no established laboratory markers for non-celiac gluten sensitivity, although a high prevalence of first generation anti-gliadin antibodies of IgG class has been reported in this condition. This study was designed to characterize the effect of the gluten-free diet on anti-gliadin antibodies of IgG class in patients with non-celiac gluten sensitivity.

Concepts: Immune system, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Rice, Wheat gluten

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BACKGROUND: The objective of this study was to compare celiac disease (CD)– specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of CD. METHODS: This retrospective study included sera from 149 CD patients and 119 controls, all with intestinal biopsy. All samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium. RESULTS: dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Positive (76% vs. 93%) and negative (72% vs. 83%) predictive values were also higher for dpgli than for ngli. Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P < 0.00001). A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00. Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01. CONCLUSION: dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium permitted diagnosis or exclusion of CD without intestinal biopsy in a high proportion of patients (78%). Jejunal biopsy would be necessary in patients with discordant antibody results (22%). With this two-step procedure, only patients with no CD-specific antibodies would be missed.

Concepts: Immune system, Antibody, Fc receptor, Glycoproteins, Positive predictive value, Negative predictive value, Antibodies, Coeliac disease

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Coeliac disease is an important clinical disorder affecting the human gastrointestinal tract leading to multiple signs and symptoms in different body organs. This disease was the subject of a cross sectional descriptive-analytic study conducted in the Gaza Strip during 2010. Objectives were oriented to identify and verify several variables and attributes affecting the prognosis of coeliac disease in the patients. Ninety five children out of 113 patients were arranged into two groups according to age from 2 to 11 years and from 12 to 18 years old. Results showed the poor interest of health professionals regarding coeliac disease in the Gaza Strip. The mean age of study population was 5.47 years for males and 8.93 years for females. The lifestyle of coeliac patients was directly proportional with better nutritional indictors. Poor recognition of the emblem illustrating gluten in foods implicates effective health awareness or promotion. The more knowledgeable patients or mothers (P = 0.036) were the more compliant. The compliance to giving gluten free foods outside home was statistically significant (P = 0.037). Similarly, cautious approach when buying foods or detergents (P = 0.011). According to BMI 74.4%, 23.4% and 3.2% of all patients were normal, underweight and overweight respectively. Albumin blood level was normal in 32.6% and low in 67.4%. Meanwhile, blood calcium level was normal in 76.8%, low in 21.1% and high in 2.1% of all patients. Conclusion: The study showed that recreation and social activities for coeliac patients are substantially missing in the Gaza Strip. Moreover, the study proved that AEI is a reliable centre for care of coeliac disease patients and conducting relevant studies. Recommendation: There is a need for thorough and continuous community and institutional mobilization regarding coeliac disease in the Gaza Strip and in Palestine.

Concepts: Coeliac disease, Gluten-free diet, Second Intifada, Gaza Strip, Palestinian territories, Palestinian National Authority, Gaza, Hamas

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BACKGROUND: A higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during alpha-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-alpha treatment might favour the development of coeliac disease in patients with chronic hepatitis C.Materials and methodsTwo hundred-ten consecutive patients (M/F = 140/70, range of age 35–58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18–74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent. RESULTS: 1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-alpha treatment was not associated with development of coeliac disease either clinical or serological. CONCLUSIONS: 1) coeliac disease is not associated with HCV infection; 2) PEG interferon-alpha does not trigger celiac disease.

Concepts: Immune system, Antibody, Osteoporosis, Hepatitis C, Hepatitis B, Coeliac disease, Anti-transglutaminase antibodies, Tissue transglutaminase

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Celiac disease is an autoimmune disorder triggered in genetically predisposed individuals by the ingestion of gluten proteins from wheat, barley, and rye. The -gliadin gene family of wheat contains four highly stimulatory peptides, of which the 33-mer is the main immunodominant peptide in celiac patients. We designed two sgRNAs to target a conserved region adjacent to the coding sequence for the 33-mer in the -gliadin genes. Twenty-one mutant lines were generated, all showing strong reduction in -gliadins. Up to 35 different genes were mutated in one of the lines of the 45 different genes identified in the wild type, while immunoreactivity was reduced by 85%. Transgene-free lines were identified, and no off-target mutations have been detected in any of the potential targets. The low-gluten, transgene-free wheat lines described here could be used to produce low gluten foodstuff and serve as source material to introgress this trait into elite wheat varieties. This article is protected by copyright. All rights reserved.

Concepts: DNA, Protein, Gene, Genetics, Amino acid, Wheat, Coeliac disease, Gluten

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Coeliac disease (CD) incidence has increased in recent decades, characterised by variations according to sex, age at diagnosis, year of birth, month of birth and region of birth. Genetic susceptibility and exposure to gluten are the necessary factors in CD aetiology, although several environmental factors are considered.

Concepts: Epidemiology, Environment, Wheat, Coeliac disease, Gluten, Gluten-free diet, Wheat allergy, Gliadin