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  • Jefferson Adams
    Jefferson Adams

    Goblet Cells Emerge as Unexpected Player in Intestinal Immunity

    Caption: Goblet Cells

    Celiac.com 05/16/2012 - Goblet cells that line the intestine and secrete mucous are emerging as a possible target for treating inflammatory bowel disease, celiac disease and food allergies.

    Goblet cellsWith every meal, immune cells in the intestine stand guard against harmful bacteria but permit vitamins and nutrients to pass. The small intestine is protected from harmful pathogens by a layer of mucus secreted from goblet cells.

    A research team at Washington University School of Medicine in St. Louis have identified the cells that protect the intestine against food antigens, or proteins so that the immune system does not begin an attack.

    The discovery of goblet cells in mice shines new light on their role in the lining of the intestine, and gives scientists a potential target for treatments against inflammatory bowel disease, celiac disease and food allergies.

    To accomplish their task, the researchers used a new imaging technique that allows them to observe the inner workings of the intestine in a living mouse in real time. For their study, they fed marked sugar to mice and observed antigens as they were passed by goblet cells to dendritic cells.

    Dendritic cells play a key role in the immune system. But until now, scientists thought that intestinal goblet cells were only responsible for secreting mucus.

    Miller and Newberry also studied healthy human intestinal tissue from patients undergoing weight-loss surgery.  Those results showed that goblet cells perform the same function in people as in mice. This indicates that the cells may be solid drug targets for treating inflammatory bowel disease and other intestinal problems.

    After studying normal, healthy mice, the researchers are now using the same imaging technique to look at how goblet cells and dendritic cells might function differently when inflammation or infection occurs.

    They also plan to study mucus-producing goblet cells in other tissues, such as the lung, to assess whether they are working the same way elsewhere in the body.

    Miller says the results are important because they help scientists understand that intestinal immune responses may depend as much on the ability of goblet cells to transport antigens to dendritic cells as on what the dendritic cells then do with those antigens.


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    Thank you for sharing this exciting research. I went to the article abstract. Too bad I can't read more... I would love to.

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, science, and advanced research, and scientific methods. He previously served as Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Jefferson Adams
    Celiac.com 03/08/2012 - Eating gluten-free for an entire lifetime is no easy task. Many people with celiac disease and gluten-sensitivities would love an alternative to a gluten-free diet, and a number of companies are looking to develop alternative therapies that would enable people to consume gluten without suffering damage.
    Even though nearly all drug-development programs include gluten challenges, very little is known about the duration of gluten challenge and gluten dosage. That is, how quickly does gluten cause damage, and at what dosages?
    A team of researchers recently studied the ways in which antibodies respond and mucosa change when the small bowel is exposed to gluten in people with celiac disease. The study team included Marja-Leena Lähdeaho, Markku Mäki, Kaija Laurila, Heini Huhtala, and Katri Kaukinen.  
    To assess the amount of gluten-exposure needed to cause some small-bowel mucosal deterioration, the team conducted a gluten-challenge on twenty-five adult celiac patients. Each patient received either a low (1-3 g) or moderate (3-5g) doses of gluten daily for 12 weeks.
    The team assessed patient symptoms, including small-bowel morphology, densities of CD3+ intraepithelial lymphocytes (IELs) and celiac serology.
    Their results showed that both moderate and low amounts of gluten induced small-bowel damage in 67% of celiac patients. However, moderate gluten doses also caused mucosal inflammation and gastrointestinal symptoms in seven patients that lead to their premature withdrawal from the study. Interestingly, 22% of patients who developed significant small-intestinal damage showed no symptoms.
    The team concludes that, for most people with celiac disease, even low amounts of gluten can cause significant mucosal changes. However, since many people with celiac disease show no such response, sample sizes must be large enough to be statistically significant.
    Source:

    BMC Gastroenterology. 2011;11(129).

    Jefferson Adams
    Celiac.com 01/14/2013 - Sweden has seen a sharp rise in cases of celiac disease in children under two years of age. A research team recently studied the possible connection between early infections and celiac disease, along with their possible role in the explosion of celiac cases in Swedish children.
    The research team included Anna Myléus, Olle Hernell, Leif Gothefors, Marie-Louise Hammarström, Lars-Åke Persson, Hans Stenlund and Anneli Ivarsson.
    They are affiliated with the Epidemiology and Global Health, Department of Public Health and Clinical Medicine at Umeå University, Pediatrics unit of the Department of Clinical Sciences at Umeå University, the Immunology unit of the Department of Clinical Microbiology at Umeå University in Umeå, Sweden, and with the International Maternal and Child Health, Department of Women's and Children's Health in Uppsala University in Uppsala, Sweden.
    The team used a questionnaire to carry out a population-based incident case-referent study. The questionnaire went out to 475 cases and 950 referents, and included questions on family characteristics, infant feeding, and the child's general health.
    All cases of celiac disease cases were diagnosed before two years of age, and fulfilled the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition.
    The team randomly selected referents, matched by criteria, from the national population register.
    The final analysis included 373 (79%) cases of confirmed celiac disease and 581 (61%) referents, for a total of 954 children.
    For each case of celiac disease, the team matched complete information on main variables of interest with one or two referents.
    The results showed that children who suffered three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life faced a significantly higher risk for later celiac disease..
    This risk remained after the team adjusted for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014).
    Infants who had several infectious episodes, and whose parents introduced dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued faced an even greater risk (OR 5.6; 95% CI, 3.1-10; P<0.001).
    This study suggests that children who suffer repeated infections before age two face an increased risk for developing celiac disease later on. The risk was even greater in children who suffered repeated infections and whose parents introduced gluten in large quantities after weening.
    The team concludes that early infections probably made a minor contribution to the rise in celiac disease cases in Swedish children relative to the amounts of gluten introduced into the children's diets after weening.
    Source:
    BMC Pediatrics 2012, 12:194 doi:10.1186/1471-2431-12-194

    Jefferson Adams
    Celiac.com 01/30/2013 - Currently, doctors diagnose celiac disease with blood tests that screen for two antibodies, one that targets gluten and another that goes after an intestinal protein. The tests work pretty well to spot advanced cases of celiac disease, but by that time, patients are already suffering intestinal damage.
    A research team looking into a method for reliable earlier detection of celiac disease focused on the responses of certain bacteria to celiac disease.
    They have built a library of peptides on the surfaces of bacteria which capture new antibodies associated with celiac disease. This, in turn, has led them to a new technique for harvesting celiac disease antibodies, which may help improve diagnosis for celiac disease, especially early on. The researchers say the technique may allow them to successfully tell, much earlier than before, which perspective celiac sufferers are sick and which are healthy.
    The research team included Bradley N. Spatola, Joseph A. Murray, Martin Kagnoff, Katri Kaukinen, and Patrick S. Daugherty. They are affiliated with the Department of Chemical Engineering at the University of California at Santa Barbara, California, the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, the Laboratory of Mucosal Immunology, Department of Medicine and the Department of Pediatrics at the University of California at San Diego in La Jolla, California and with the Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
    For their study, Patrick Daugherty, of the University of California, Santa Barbara, and his team aimed to find previously unknown disease-linked antibodies. Their strategy centered on building an enormous library of random peptide sequences to find ones that would bind to the antibodies.
    To create their library, the researchers inserted one billion random peptide genes into Escherichia coli, with one peptide gene per bacterium.
    Once the genes were expressed inside the bacteria, thousands of copies of the peptides migrated to the cells’ surface. The researchers hoped that some of these peptides would bind antibodies from the blood of people with early-stage celiac disease, but not those in samples from healthy people.
    The team hoped that their approach, with numerous bacteria each bearing a different peptide, would be more likely to identify unknown antibodies than are current types of peptide libraries, which must be mounted on hard surfaces.
    To test their new library approach, the researchers collected blood samples from 40 healthy people and 45 people who had been diagnosed with celiac disease.
    They purified antibodies from the blood samples, then labeled antibodies from half the celiac patients with a green fluorescent dye and the rest of the patients’ antibodies with a red dye.
    They then mixed the peptide-coated bacteria together with all the antibodies, adding five times as many unlabeled antibodies from the healthy subjects to block labeled antibodies from binding to peptides found in people with and without celiac disease.
    Next, they sorted the cells, collecting only those bacteria displaying both red and green fluorescence.
    Cells labeled with both dyes, the researchers reasoned, help a peptide that could bind to an antibody found in at least two people, one patient from each group. These antibodies, they say, could be markers for celiac disease.
    Additional screening of the peptides with antibodies from healthy patients and those with celiac disease, the researchers narrowed the bacterial pool down to six unique peptides, none of which bind to known celiac antibodies.
    The researchers then measured binding between these peptides and the full suite of antibodies from patients’ blood. Based on that data, they used a statistical analysis to conclude that they could identify correctly 85% of people with celiac disease and 91% of healthy – nearly matching the values of existing diagnostic tests.
    It remains uncertain whether this approach will permit doctors to diagnose celiac disease at earlier stages than current methods, but the results look promising, and the team remains hopeful.
    Daugherty says that the method is applicable to other immune disorders, including difficult-to-diagnose illnesses such as lupus, multiple sclerosis, and some cancers.
    Source:
    Anal. Chem., 2013, 85 (2), pp 1215–1222. DOI: 10.1021/ac303201d

    Jefferson Adams
    Celiac.com 02/06/2013 - Villous atrophy (VA) in the small intestine is one of the prime features of celiac disease, and has been associated with increased mortality, but it is unknown if mortality is influenced by mucosal recovery.
    To better understand the relationship between mucosal healing and mortality in celiac disease, a research team set out to determine whether persistent villous atrophy is associated with mortality in celiac disease patients.
    The research team included B. Lebwohl, F. Granath, A. Ekbom, S.M. Montgomery, J.A. Murray, A. Rubio-Tapia, P.H. Green, and J.F. Ludvigsson. They are variously affiliated with the Celiac Disease Center at the Department of Medicine of Columbia University College of Physicians and Surgeons in New York, NY, the Clinical Epidemiology Unit at the Department of Medicine of Karolinska University Hospital and Karolinska Institutet in Stockholm, Sweden.
    The team used biopsy reports from every pathology department (n = 28) in Sweden to identified 7,648 individuals with celiac disease, which they defined as the presence of villous atrophy, and who had undergone a follow-up biopsy within 5 years of diagnosis. They used Cox regression to assess mortality according to follow-up biopsy.
    Celiac patients were 28.4 years of age, on average, and 63% were female. The average follow-up after diagnosis was 11.5 years. Overall, patients who underwent follow-up biopsy had lower mortality rates than those who did not undergo follow-up biopsy (Hazard Ratio 0.88, 95% CI: 0.80-0.96).
    Of the 7648 patients who underwent follow-up biopsy, 3317 (43%) showed persistent villous atrophy. In all, 606 (8%) patients died. However, patients with persistent villous atrophy died at about the same rates as those with mucosal healing (HR: 1.01; 95% CI: 0.86-1.19).
    Also, children with persistent villous atrophy showed no increase in mortality (HR: 1.09 95% CI: 0.37-3.16) or adults (HR 1.00 95% CI: 0.85-1.18), including adults older than age 50 years (HR: 0.96 95% CI: 0.80-1.14).
    Mortality rates for celiac patients with persistent villous atrophy are about the same as for celiac patients with healthy guts. So, persistent villous atrophy is not tied to higher mortality for celiac disease patients. That means that even though a follow-up biopsy will help doctors to spot refractory disease in symptomatic patients, persistent villous atrophy is not useful in predicting future mortality.
    Source:
    Aliment Pharmacol Ther. 2013 Feb;37(3):332-9. doi: 10.1111/apt.12164.

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