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    Pentraxin 3 Tied to Major Gastrointestinal Damage in Celiac Disease Patients


    Jefferson Adams
    • A pair of researchers recently set out to assess the relationship between Pentraxin 3 and biopsy status in celiac patients.

    Pentraxin 3 Tied to Major Gastrointestinal Damage in Celiac Disease Patients
    Image Caption: Image: CC--altemark

    Celiac.com 09/11/2018 - Gluten sensitivity is the most common sign of celiac disease. Clinical celiac diagnosis usually involves a positive blood test followed by biopsy confirmation of a typical enteropathy.

    The body’s immune response to celiac disease involves both adaptive and innate immunity, and is marked by anti-gliadin (AGA) and anti-transglutaminase 2 antibodies (tTGA), lymphocytic infiltration in the intestinal epithelial membrane, and expression of multiple cytokines. Researchers know that long pentraxin 3 (PTX3), an acute-phase inflammatory molecule, plays an important role in innate immunity.

    A pair of researchers recently set out to assess the relationship between Pentraxin 3 and biopsy status in celiac patients. Roberto Assandri and Alessandro Montanelli of the Department of Clinical Pathology, Clinical Chemistry Laboratory ASST Ospedale Maggiore di Crema, Italy, and the Clinical Chemistry Laboratory, Spedali Civili di Brescia, Italy, set out to explore a possible relationship between PTX3 and celiac disease.

    They used Marsh Histological grade following Marsh criteria classification to dividing 108 celiac disease patients into three groups: Group 1: Marsh 0, patients with a known history of celiac disease under gluten free diet, complete remission; Group 2: Marsh 1 and Marsh 2; Group 3: Marsh 3.

    As a control group, they used 30 healthy age-matched individuals with no known history of celiac disease or gastrointestinal symptoms. They used sandwich ELISA on an automated platform to measure PTX3 serum levels.

    They found that PTX3 serum levels were substantially higher in group 3 and group 2 compared with the healthy control group. They found no statistically significant differences between group 1 and the healthy control group. They noted a strong linear correlation between PTX3 serum levels and AGA levels in group 2, and group 3, but no such correlations between PTX3 serum levels and tTGA levels. 

    Blood tests showed that PTX3 correlated with major gastrointestinal damage in celiac patients. PTX3 is a part of the innate immune system’s humoral branch. Data from this study show that PTX3 serum levels are high in active disease patients with pathological levels of AGA. They also show that patients with normal AGA IgA levels had PTX3 serum levels compared to healthy control subjects. 

    The team proposes that PTX3 can modulate the innate response to gliadin in celiac disease, and may also regulate the adaptive immune response. 

    Read more at: Gastroenterology and Hepatology

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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, and science. He previously served as Health News Examiner for Examiner.com, and provided 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 Dangerous Grains by James Braly, MD and Ron Hoggan, MA.

  • Related Articles

    Jefferson Adams
    Celiac.com 07/10/2007 - A study published recently in the American Journal of Gastroenterology tracks the appearance and disappearance of antibodies associated with childhood risk celiac disease, and suggests that key antibodies often disappear even when gluten is still present in the diet.
    A team of Finnish doctors set out to evaluate the natural history of antibodies versus tissue transglutaminase (TGA), endomysium (EMA), reticulin (ARA), and gliadin (AGA-IgG and AGA-IgA). They looked at data for children genetically at risk for celiac disease, specifically, children who carried HLA-conferred risk of celiac disease who had been monitored frequently since birth. The research team was made up of S. Simell, S. Hoppu, A. Hekkala, T. Simell, M.R. Ståhlberg, M. Viander, H. Yrjänäinen, J. Grönlund, P. Markula, V. Simell, M. Knip, J. Ilonen, H. Hyöty, O. Simell.
    The team looked at serum samples from 1,320 children who were genetically at risk for celiac disease. Serum samples taken between 2000 and 2003 were assessed for TGA. Samples testing positive for TGA were evaluated for all five antibodies. Also, all future samples for the given patient were similarly evaluated. Also, positive TGA patients were encouraged to have a duodenal biopsy.
    The assessment was completed in August 2004. At that time, the test subjects ranged in age from 1 year to 9.5 years, with a mean age of 4.1 years. In all, 49 children (3.7%) were TGA positive. 26 of these TGA positive children submitted to biopsy. Celiac disease was diagnosed by biopsy in 20 of the 26. Of the 49 children who tested TGA positive, AGA-IgA surfaced at an average age of 2 years (+/- 1.5 over a range of 0.5 to 6.6 years for subjects). Compared to AGA-IgA, TGA, EMA, and ARA all surfaced together about 1 year later (TGA at 3.2 +/- 1.5, 1.0-7.0 yr, P < 0.001).
    Key Antibodies Can Vanish Early in Childhood Celiac Disease
    Even with ongoing gluten consumption, positive TGA values disappeared in 49%, EMA values disappeared in 49%, ARA values disappeared in 43%, AGA-IgA values disappeared in 41%, and AGA-IgG in 32%.
    The research team concluded that there are likely potential triggers for celiac disease that are active before AGA-IgA surfaces, or about 3 months earlier on average than when the TGA-associated antibodies appear.
    In a significant number of children, antibodies vanish spontaneously. This indicates that in many cases, conditions allow the regulatory immune phenomena to eliminate incipient celiac disease in genetically at-risk children even when gluten is still significant part of the diet.
    Am J Gastroenterol 2007;102:1–10
     

    Jefferson Adams
    Gliadin Triggers Innate Immune Reaction in Celiac and Non-celiac Individuals
    Celiac.com 12/31/2012 - In people with celiac disease, eating wheat, barley, or rye triggers inflammation in the small intestine. Left unchecked, this inflammation causes the gut damage that is associated with untreated celiac disease.
    Specifically, the storage proteins in these grains (gluten) trigger an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition.
    Researchers actually have a pretty good understanding of this aspect of celiac disease, part of a process called adaptive immunity.
    However, there has been some research that suggests that gluten proteins might trigger an immune response in people who do not have celiac disease, and who do not carry the HLA-DQ2 or HLA-DQ8 genetic markers that predispose them to developing celiac disease. Such a response is part of a process called innate immunity, and is far less understood than the adaptive immunity process.
    The innate immune system provides an early response to many microbial and chemical stimuli and is critical for successful priming of adaptive immunity.
    To better understand the relationship between adaptive immunity and innate immunity in celiac disease, a research team recently set out to determine if gliadin digests might induce innate immune responses in celiac and non-celiac individuals.
    Specifically, they wanted to know if wheat amylase trypsin inhibitors drive intestinal inflammation, and if so, by what receptor mechanism.
    The research team included Yvonne Junker, Sebastian Zeissig, Seong-Jun Kim, Donatella Barisani, Herbert Wieser, Daniel A. Leffler, Victor Zevallos, Towia A. Libermann, Simon Dillon, Tobias L. Freitag, Ciaran P. Kelly, and Detlef Schuppan. They are affiliated variously with the Division of Gastroenterology and the Proteomics and Genomics Center at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, with the Department of General Pediatrics and the Department of Internal Medicine I at the University Medical Center Schleswig-Holstein Kiel in Kiel, Germany, the Department of Experimental Medicine at the University of Milano-Bicocca in Milan, Italy, the German Research Center for Food Chemistry in Garching, Germany, the Hans-Dieter-Belitz-Institute for Cereal Grain Research in Freising, Germany, the Division of Molecular and Translational Medicine in the Department of Medicine I at Johannes Gutenberg University in Mainz, Germany, and with the Department of Bacteriology and Immunology at the Haartman Institute at the University of Helsinki in Finland.
    A number of earlier studies (Molberg et al., 1998; Anderson et al., 2000; Shan et al., 2002) have found HLA-DQ2– and HLA-DQ8–restricted gluten peptides that trigger the adaptive immune response in people with celiac disease. However, only 2–5% of individuals who show these HLAs develop celiac disease, which means that other factors, especially innate immune activation, are at play in the generation of celiac disease.
    Responsive innate cells are primarily macrophages, monocytes, DCs, and polymorphonuclear leukocytes that by means of their pattern-recognition receptors, such as TLRs, trigger the release of proinflammatory cytokines and chemokines, resulting in recruitment and activation of additional inflammatory cells (Medzhitov, 2007). Earlier studies (Maiuri et al., 2003) showed that peptides p31-43 or p31-49 from α-gliadin, that lack adaptive stimulatory capacity, triggered innate immune reactions by inducing IL-15 and Cox-2 expression in patient biopsies, and MHC class I polypeptide–related sequence A (MICA) on intestinal epithelial cells (Hüe et al., 2004).
    However, these studies have proven difficult to reproduce in cell culture, and researchers could not identify any specific receptor responsible for the observed effects. In a subsequent study, gliadin, in cell culture, reportedly triggered increased expression of co-stimulatory molecules and the production of proinflammatory cytokines in monocytes and DCs (Nikulina et al., 2004; Cinova et al., 2007).
    Two other studies (Thomas et al., 2006; Lammers et al., 2008) implicated the chemokine receptor CXCR3 in increased intestinal epithelial permeability upon gliadin challenge in a MyD88-dependent manner. However, those studies failed to reproducibly identify a specific gliadin peptide as the trigger.
    So far, no clear picture of the role of the innate immune system in celiac disease has emerged. In this study, the researchers show that members of the non-gluten α-amylase/trypsin inhibitors (ATIs), CM3 and 0.19, pest resistance molecules in wheat and related cereals, are strong triggers of innate immune responses in human and murine macrophages, monocytes, and dendritic cells.
    Their results show that ATIs activate the TLR4–MD2–CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients’ biopsies.
    They also show that mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs.
    These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.
    The findings of this study mean that the proteins in wheat may trigger immune reactions not just in people with celiac disease, but in people without celiac disease, and that these reactions may be actively contributing to the development of numerous other intestinal and non-intestinal immune disorders. That's a pretty big deal. Stay tuned to see how future studies elaborate these findings.
    Read the entire study in the Journal of Experimental Medicine.
    Source:
    J Exp Med. 2012 Dec 17;209(13):2395-408. doi: 10.1084/jem.20102660

    Jefferson Adams
    Does Autoimmune Disease Carry Higher Risk of Dementia?
    Celiac.com 04/13/2017 - A team of researchers recently set out to determine whether hospital admission for autoimmune disease is associated with an elevated risk of future admission for dementia.
    The research team included Clare J Wotton, and Michael J Goldacre, both affiliated with the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
    The pair set up their retrospective, record-linkage cohort study using national hospital care and mortality administrative data from 1999–2012. From that patient data, they assembled a study group of people admitted to hospital with a range of autoimmune diseases, along with a control group, and followed forward in time to see if how many patients eventually developed dementia.
    Data revealed a total of 1,833,827 people admitted to hospital with an autoimmune disease. The number of patients for each autoimmune disease group ranged from 1,019 patients in the Goodpasture's syndrome group, to 316,043 people in the rheumatoid arthritis group.
    The researchers found that the rate ratio for dementia after admission for an autoimmune disease, compared with the control cohort, was 1.20 (95% CI 1.19 to 1.21). For patients whose dementia type was specified, the rate ratio ranged from 1.04 to 1.08 for Alzheimer's disease, and 1.26 to 1.31 for vascular dementia.
    Of the 25 autoimmune diseases studied, 18 showed significant positive associations with dementia, 14 of which were statistically significant. Significant associations include Addison's disease (1.48, 1.34 to 1.64), multiple sclerosis (1.97, 1.88 to 2.07), psoriasis (1.29, 1.25 to 1.34) and systemic lupus erythematosus (1.46, 1.32 to 1.61).
    The connections with vascular dementia may be one aspect of a wider connection between autoimmune diseases and vascular damage. Though findings were significant, effect sizes were small. Researchers advise clinicians to note the possibility of dementia in patients with autoimmune disease.
    The researchers are calling for further studies to assess their findings and to explore possible ways to reduce any increased risk.
    Source:
    BMJ

    Jefferson Adams
    Can Targeting Gut Bacteria Prevent Autoimmune Disease?
    Celiac.com 04/25/2018 - A team of Yale University researchers discovered that bacteria in the small intestine can travel to other organs and trigger an autoimmune response. In this case, they looked at Enterococcus gallinarum, which can travel beyond the gut to the spleen, lymph nodes, and liver. The research could be helpful for treating type 1 diabetes, lupus, and celiac disease.
    In autoimmune diseases, such as type 1 diabetes, lupus, and celiac disease, the body’s immune system mistakenly attacks healthy cells and tissues. Autoimmune disease affects nearly 24 million people in the United States. 
    In their study, a team of Yale University researchers discovered that bacteria in the small intestine can travel to other organs and trigger an autoimmune response. In this case, they looked at Enterococcus gallinarum, which can travel beyond the gut to the spleen, lymph nodes, and liver. They found that E. gallinarum triggered an autoimmune response in the mice when it traveled beyond the gut.
    They also found that the response can be countered by using antibiotics or vaccines to suppress the autoimmune reaction and prevent the bacterium from growing. The researchers were able to duplicate this mechanism using cultured human liver cells, and they also found the bacteria E. gallinarum in the livers of people with autoimmune disease.
    The team found that administering an antibiotic or vaccine to target E. gallinarum suppressed the autoimmune reaction in the mice and prevented the bacterium from growing. "When we blocked the pathway leading to inflammation," says senior study author Martin Kriegel, "we could reverse the effect of this bug on autoimmunity."
    Team research team plans to further investigate the biological mechanisms that are associated with E. gallinarum, along with the potential implications for systemic lupus and autoimmune liver disease.
    This study indicates that gut bacteria may be the key to treating chronic autoimmune conditions such as systemic lupus and autoimmune liver disease. Numerous autoimmune conditions have been linked to gut bacteria.
    Read the full study in Science.

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    • Maureen and Cyclinglady, Of the foods you listed. . .. I would focus on the Chocolate. Chocolate has Tyramine in it and it could/can cause rashes that  might be confused for DH. Sometimes Tyramine get's confused for/in high sulfite foods as triggers. Here is a great overview article on this topic. http://www.chicagotribune.com/lifestyles/health/sc-red-wine-headache-health-0608-20160525-story.html you might also have trouble with headaches if it tyramine is causing you your trouble. People who have trouble Tyramine might also have trouble with consuming cheeses. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738414/ As for the Milk causing/triggering your DH don't rule Adult onset dairy allergy. While rare it does occur in the literature/research when you search it out. I am including the research here in the hopes it might help you or someone else entitled "Adult onset of cow's milk protein allergy with small‐intestinal mucosal IgE mast cells" https://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.1996.tb04640.x It is generally thought most of grow out of a Milk Allergy at approx. 3 years old. But for some lucky one (I guess) we never do apparently.  (I speak for my friend on this board JMG).  He found out he was having trouble with dairy as an adult better never realized until about 6 months ago. With delayed onset allergies it is often hard to tell if it (allergen) is effecting us because we might not associate it with our dairy consumption because it might happen a day or two latter. See this WHFoods article about food allergens/sensitivies.  It is very long/exhaustive but it is very helpful if you have time to study it in more detail. http://www.whfoods.com/genpage.php?pfriendly=1&tname=faq&dbid=30 I will quote some key points for your information. Symptoms of Food Allergies "The most common symptoms for food allergies include vomiting, diarrhea, blood in stools, eczema, hives, skin rashes, wheezing and a runny nose. Symptoms can vary depending upon a number of variables including age, the type of allergen (antigen), and the amount of food consumed. It may be difficult to associate the symptoms of an allergic reaction to a particular food because the response time can be highly variable. For example, an allergic response to eating fish will usually occur within minutes after consumption in the form of a rash, hives or asthma or a combination of these symptoms. However, the symptoms of an allergic reaction to cow's milk may be delayed for 24 to 48 hours after consuming the milk; these symptoms may also be low-grade and last for several days. If this does not make diagnosis difficult enough, reactions to foods made from cow's milk may also vary depending on how it was produced and the portion of the milk to which you are allergic. Delayed allergic reactions to foods are difficult to identify without eliminating the food from your diet for at least several weeks and slowly reintroducing it while taking note of any physical, emotional or mental changes as it is being reintroduced." Here is their information on Tyramine's. Tyramine "Reactions to tyramine (an amino acid-like molecule) or phenylalanine (another amino acid-like molecule) can result from eating the following foods: Fermented cheeses Fermented Sausage Chocolate Sour Cream Red wine Avocado Beer Raspberries Yeast Picked Herring Symptoms of tyramine intolerance can include urticaria (hives), angioedema (localized swelling due to fluid retention), migraines, wheezing, and even asthma. In fact, some researchers suggest that as many as 20 percent of migraines are caused by food intolerance or allergy, and tyramine intolerance is one of the most common of these toxic food responses." Here is an old thread on tyramine and especially how it can trigger headaches. https://www.celiac.com/forums/topic/95457-headache-culprit-is-tyramine/ I would also suggest your research a low histamine food diet.  Rashes/hives etc. can be triggered my disregulaton of histamine in the body. The other thing in chocolate that might be causing your problems is Sulfites. Here is a website dedicated to a Sulftie allergy. http://www.allergy-details.com/sulfites/foods-contain-sulfites/ Chocolate bars are on their list of sulfite contaning foods but probably most noted in dried fruits and red wine. Knitty Kitty on this board knows alot about a sulfite allergy. I want to go back to the possible dairy allergy for a second as a possible trigger. . .because it has been established as connected to DH . . .it is just not well known. Here is current research (as I said earlier) most dairy allergies are studied in children but it does occur in approx. 10 pct of the GP unless your of Asian descent where it is much more common. https://www.ncbi.nlm.nih.gov/pubmed/29555204 quoting the new research from this year on children. "When CMP (Cow's Milk Protein) was re-introduced, anti-tTG increased, and returned to normal after the CMP was withdrawn again." and if adults can also (though rarely) it seem develop "Adult onset of cow's milk protein allergy with small‐intestinal mucosal IgE mast cells" (see research linked above) as the research shows  you should at least trial removing dairy from your diet if you haven't already and see if your DH doesn't come back when you re-introduce it. It just takes 15 or 20 years for medical doctor' to incorporate new research/thinking into clinical practice.  And note the research on this happening in adults is 20+ years old and as far I know doctor's . . . are not aware of this.  I know I wasn't until recently and I research things alot of to help myself and my friends. But I know you can't do what you don't know about.  So this is why I am trying to share what I learned so that other might be helped and this research might not  lay hidden another 20 years before doctor's and their Celiac/DH patients become aware of it. And if it helps you come back on the board and let us know so it can help others too! If it helps you it will/can help someone else! if they know it helped you then they will/can have hope it might help them too and why I share and research these things for others'. . . who don't know or don't have time to research this for themselves. I hope this is helpful but it is not medical advice. Good luck on your continued journey. I know this is a lot of information to digest at one time but I hope at least some of if it helpful and you at least have a better idea of what in your chocolate could be causing your DH (idiopathic) as the doctor's say (of an unknown cause mild) DH symptom's. Or at least it is not commonly known yet that Milk can also cause trigger (DH) in children and adults who have a Milk allergy undiagnosed. . .because we don't don't typically think  or associate it with adults like maybe we should if we are not of Asian descent. Maureen if this doesn't help you you might want to start a thread in the DH section of the forum. As always  2 Timothy 2: 7   “Consider what I say; and the Lord give thee understanding in all things” this included. Posterboy by the grace of God,
    • I hooe you can get some answers with your new GI doc.
    • Many of us deal with doctor issues and diagnosis, you got a really bad draw indeed. Most doctors dismiss Celiac as their is no money in the cure for them IE a gluten free diet and not medications.

      Keep up updated on your new doctor and testing, good to see you finally found one that listens and can help, I got through on doc #5 I think it was.
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