Tag Archives: celiac research

CeliAction Study Update

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Even when you try your best to stay gluten-free, you never know for sure if something you’ve eaten has been cross-contaminated or mislabeled until after the fact. Most people with celiac disease can relate to accidentally ingesting gluten and then paying the price later on.

Well, there is research currently underway to evaluate if an investigational drug can reduce the symptoms of unintentional exposure to gluten. If proven effective, the drug would offer a new way to manage celiac disease and supplement a gluten-free diet by reducing the risk of gluten’s impact on the body. The best part is that you have to stay on your gluten-free diet in order to participate – no gluten challenge!

The clinical research study is called the CeliAction Study and you may qualify if you:

  • Have been diagnosed with celiac disease by a healthcare professional
  • Are attempting to be on a gluten-free diet
  • Have experienced at least one moderate or severe symptom of celiac disease in the past month

If you participate in the CeliAction Study, you:

  • Will be able to maintain your current diet restrictions
  • Will be provided with study-related care at no cost
  • Do not need medical insurance to take part
  • May be compensated for time and travel
  • Will help advance medical research for celiac disease

To learn more about this research study and see if you qualify, visit www.CeliActionStudy.com
or call 1-855-3333-ACT.

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“Celiac Disease Now”

Note: This is part 2 of several posts summarizing information discussed at the International Celiac Disease Symposium (ICDS) 2013 in Chicago 9/23-9/25. 

The introductory lecture of the clinical forum of the International Celiac Disease Symposium (ICDS) 2013 in Chicago last week was entitled “Celiac Disease Today: An Overview” given by Drs. Alessio Fasano and Peter Green.

Although the official slides and presentations from the symposium are not yet available for purchase, based on my notes the following topics were addressed during this opening session:

Celiac Disease involves both an innate and an adaptive immune system response to gluten. 1 in 133 Americans have Celiac Disease. The risk of Celiac Disease in 1st degree relatives of Celiac patients (parents, siblings, and children) is 1 in 22. The risk in 2nd degree relatives (aunts and uncles and grandparents) is 1 in 39.  Research has shown that the true prevalence of Celiac Disease has increased by 15% in the last few decades.  Most people with Celiac Disease (83%) are unaware that they have it…

Although the current “gold standard” for diagnosing Celiac Disease is to perform an endoscopy and small intestinal biopsy, Dr. Fasano did bring up the concept of the “4 out of 5” rule, in which some have proposed that Celiac Disease can be diagnosed if a patient meets at least 4 of the following 5 criteria:

  1. Adverse symptoms when gluten is ingested
  2. Elevated Celiac antibodies on serology (blood tests)
  3. An improvement in symptoms when gluten is removed from the diet
  4. Genetic markers (HLA DQ2 and/or 8, although he did mention that 1-2% of Celiacs are DQ2 and DQ8 negative)
  5. Abnormal small intestinal (duodenal) biopsy

Anti-TTG IgA antibodies are greater than 95% sensitive and 95% specific for Celiac Disease.  The DGP IgA antibodies have a sensitivity and specificity of greater than 90%.

No one is born with Celiac Disease and it can develop at any age. Celiac Disease involves a shift from gluten tolerance to an immune (autoimmune) response to gluten.  The current thinking is that in order to develop Celiac Disease, one must have a genetic predisposition, ingest gluten, and be exposed to a (yet to be defined) environmental factor. In order to figure out exactly what the environmental factor(s) are, researchers will need to follow a large cohort of children from birth and monitor them for the development of Celiac Disease.  We did learn later during the conference that this is actually being done as part of the “Prevent Celiac Disease Study” in Europe, which I will discuss in a later post (www.preventCD.com).

It is now believed that a change in the gut microbiome (bacteria) is involved in the pathogenesis and development of Celiac Disease.  Although our gut microbiomes are inherited from our mothers,  the composition of our gut bacteria is continually changing.  There has been some recent research showing that birth by c-section increases a child’s risk of Celiac Disease by 2-3x. During a normal vaginal delivery newborns’ digestive tracts are colonized by bacteria that they pick up from their mothers’ bodies during labor and delivery.  During a c-section this mother to infant transfer of bacteria does not take place.

There are over 70 clinical trials of Celiac Disease going on right now, many of which are currently enrolling subjects.  You can check out www.clinicaltrials.gov and search for “celiac disease” for more information.

Dr. Green stated that currently recognized gluten related disorders include Celiac Disease, gluten ataxia, dermatitis herpetiformis, wheat allergy, and non celiac gluten sensitivity (NCGS).  NCGS was discussed at the ICDS pre-conference (see my previous post for more details).  Celiac Disease can be differentiated from these disorders by the presence of intestinal inflammation and villous atrophy.  Based on a 2012 publication, only 17% of people with Celiac Disease have actually been diagnosed. Young men in the age range of 20-30 have the lowest rates of diagnosis.

Currently recognized risk factors for Celiac Disease include formula feeding, being introduced to gluten before 4 months of life or after 7 months of life, being born during the winter months, PPI (proton pump inhibitor, a type a reflux medication) use, and frequent respiratory infections during infancy.  Much of this information comes from Sweden, where there was an epidemic of Celiac Disease in children during the 1980s and 1990s which triggered much research and analysis.

We were cautioned of a few pitfalls in the diagnosis of Celiac Disease, many of which I will describe in more detail in future posts.  Some of the researchers have found that TTG (tissue transglutaminase) antibody testing from certain labs can be unreliable.  Likewise, some research has shown that only 35% of the biopsies performed during evaluations for Celiac Disease are done correctly. Most GI docs take only 2 samples of small bowel, despite the current recommendations that 4-6 samples be taken.

Although Celiac Disease is often associated with digestive symptoms, many patients do not have any symptoms at all (i.e. they are picked up because they are screened due to having a family member with Celiac).  Some of the most severe cases of Celiac Disease have been found in patients whose only symptom is anemia (low red blood cell count).  On the flip side, a 2009 study showed that only 51% of patients with symptoms of Celiac Disease were actually screened.

A few sort of depressing stats:

-only 20% of patients with Celiac Disease have adequate follow-up after diagnosis

-the average U.S. medical student learns about Celiac Disease for one hour during medical school (I can personally relate to this one!)

And things that I think everyone should know:

-If a patient has dermatitis herpertiformis (DH), then they have Celiac Disease. Dr. Green stated that if one has DH, there is no need for a small bowel biopsy.

-1st degree family members of Celiac Disease patients should be screened every 5 years.

-The Celiac Center at Beth Israel Deaconess Medical Center in Boston has a great new website called “Celiac Now.” Check it out here.

More ICDS information to come soon…Also, any questions are welcome in the meantime!

 

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Recap of Non Celiac Gluten Sensitivity ICDS Pre-Conference 9.22.2013

I was fortunate to be able to attend the International Celiac Disease Symposium (ICDS) in Chicago last week, during which I was able to hear lectures given by world expert doctors, researchers, and nutritionists.  Although I got home 3 days ago, my mind is still spinning from all of the information that I learned and tried to absorb during the 22 hours of lectures.  I was also fortunate to meet some awesome people from the Celiac internet community, including Erica from Celiac and the Beast, Rebecca from Pretty Little Celiac, G-Free Laura, and The Gluten-Free Professor. Although I was not one of the official bloggers from the conference, I did learn some information that I’d like to share with you.

Over the next few weeks I plan to summarize much of the information that I learned about both Celiac Disease and Non Celiac Gluten Sensitivity (NCGS) at the symposium, as well as to try to convince you to attend the next ICDS in Prague in 2015 with me, as my dear husband has already declined.

On Sunday night there was a pre-conference on NCGS with a panel of speakers who are world’s experts on NCGS.  I am very interested in this topic as I have several family members who have NCGS and I am amazed by the lack of awareness of this condition in the medical community. There are many doctors who believe that you cannot get sick from gluten unless you have Celiac Disease (intestinal damage) and as you may already know, this is not true!

The experts who presented information about NCGS included Drs. Fasano, Green, Kelly, Mooney, Volta, Schuppan, and Leffler. Below is a summary of some of the information that was shared with the audience:

Patients with NCGS experience adverse symptoms after ingesting gluten but they do not meet the criteria for getting diagnosed with Celiac Disease (namely, they do not have the findings of Celiac Disease on small bowel biopsy).  NCGS is a “diagnosis of exclusion” meaning that, ideally, Celiac Disease is ruled out before a diagnosis of NCGS is given. Despite this, many with NCGS are self-diagnosed.

Between 0.5 to 6% of U.S. population has NCGS, depending on which study is referenced.  The average age of diagnosis is around 40 years, but the research on NCGS is really still in its infancy. Some patients with NCGS have abnormally high antibodies that are associated with Celiac Disease, such as TTG IgA and/or anti-gliadin antibodies, and others do not. About half of patients with NCGS have one of the two main Celiac genes (HLA-DQ2 and/or DQ8) and half do not.  There are currently no biomarkers for NCGS, which plays a large part in the difficulty of diagnosis.

In a large Italian survey, the most common symptoms associated with NCGS included abdominal pain, bloating, diarrhea, fatigue, headache, anxiety, and a “foggy mind.” This mirrors the symptoms that have been described in previous studies.

Dr. Green introduced the acronym PWAWG which stands for People Who Avoid Wheat and Gluten.  According to Dr. Green, not all PWAWGs have NCGS, and many have other problems such as small intestinal bacterial overgrowth (SIBO) and fructose intolerance.  In one recent study, which has gotten a lot of attention, many NCGS patients’ reactions to gluten totally disappear when FODMAPs are also removed from the diet (see link to paper in references below).  However, the researchers only looked for a resolution of abdominal and digestive symptoms and we do not know if other symptoms of NCGS, such as headaches and anxiety, also improved when FODMAPs were removed.  More research is needed in this area. Although I will discuss FODMAPs more in the upcoming weeks, you can refer to Stanford’s website for more information on the low FODMAP diet if interested.

I learned that both autism and schizophrenia have been associated with anti-gliadin antibodies. There was a publication in 2011 that showed that there is subset of autistic children whose symptoms improve on a gluten free and casein free diet.  There are also ongoing clinical trials to see if the GF diet can help improve symptoms associated with schizophrenia.  The tissue transglutaminase antibody (TTG) type 6 looks to be a marker of neuroinflammation and is a possible biomarker for schizophrenia. TTG type 2 antibodies are what are currently measured in blood tests for Celiac Disease.

The pathogenesis of NCGS appears to involve the innate immune system and it is possible that wheat amylase trypsin inhibitors (ATIs), a totally different portion of wheat than the gluten proteins, may be involved. I wrote about this a bit last winter (see link) and the article referenced can be found in the references below.

During the panel discussion, we were reminded that the only way that a NCGS individual who is already GF can find out if he or she has Celiac Disease is to undergo a “gluten challenge.”

One of the last questions to the panel was, “Who should be avoiding gluten?” The answer given was patients with Celiac Disease, NCGS, and possibly autism and schizophrenia.

I also learned that Dr. Fasano recently published a book called “A Clinical Guide to Gluten-Related Disorders,” which I plan to purchase a copy of ASAP. It is available on Amazon.com (see here).

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Dr. Fasano reminded us that there is currently more confusion than understanding of NCGS, and that it is similar where we were with understanding Celiac Disease 20 to 30 years ago. The great thing is NCGS is finally being recognized and properly studied!

For a great overview of NCGS, please check out the following abstract from PubMed by Dr. Volta, who was one of the experts on NCGS at the symposium:

Volta U, Caio G, Tovoli F, De Giorgio R.Cell Mol Immunol. Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness.  2013 Sep;10(5):383-92. doi: 10.1038/cmi.2013.28. Epub 2013 Aug 10.

Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues.

Additional References from ICDS pre-conference:

1. DiGiacomo, et al. Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the Continuous National Health and Nutrition Examination Survey 2009-2010. Scand Journal Gastroenterol. 2013 Aug;48(8):921-5. doi: 10.3109/00365521.2013.809598. Epub 2013 Jul 8.

2. Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol 2011;106:508–14.

3. Biesiekierski JR., et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology. 2013 Aug;145(2):320-8.e1-3. doi: 10.1053/j.gastro.2013.04.051. Epub 2013 May 4.

4. Junker, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012 Dec 17;209(13):2395-408. doi: 10.1084/jem.20102660. Epub 2012 Dec 3.

 

 

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Celiac Disease “Journal Club” 2013 Part 1

As some of you may have figured out, I love to keep up to date with the latest research regarding celiac disease and non-celiac gluten sensitivity (NCGS). My interest in research stems from the countless Journal Clubs that I participated in during my decade of medical training. Journal Club gives medical students, residents, fellows, and other trainees the opportunity to learn how to read, interpret, and critically review research articles. Although there are many things which I do not miss about medical training (especially the sleep deprivation), I do miss Journal Club.

I have created my own overview for you of some of the most interesting research articles about gluten-related diseases that have been published during the past few months. This is part 1 of 2.

1. “Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease.” Authors: Pulido, et al. Published in the Canadian Journal of Gastroenterology in August 2013.

-Almost 6000 adults with Celiac Disease were surveyed regarding their symptoms of Celiac Disease and their recovery on the GF diet. Average age at diagnosis was 45 and average delay in diagnosis was 12 years.

-Conclusions: Although many subjects had a complete resolution of symptoms after 5 years on the GF diet, almost half reported continuing problems with migraines, lactose intolerance, constipation, itchy skin, and depression after being GF for 5 years. Women were less likely than men to report full recovery from symptoms, especially in the areas of abdominal pain, bloating, weakness, diarrhea, anemia, muscle cramps, constipation, migraine headaches, and swelling of the hands and feet.

2.  “Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study.” Authors: Lebwohl, et al. Published in Annals of Internal Medicine in August 2013.

-Researchers found that 43% of adults with Celiac Disease in their study population had persistent villous atrophy on follow-up biopsies after being GF. These patients were found to have a significantly higher (3.5x) risk of lymphoma than the general population.

-Conclusion: Partially treated Celiac Disease is associated with cancer.

-For more information please check out this summary article from Columbia University.

3. “Antibiotic exposure and the development of celiac disease: a nationwide case-control study.” Authors: Marild, K., et al. Published in BMC Gastroenterology in July 2013.

-Main objective of the study was to examine the association between antibiotic use and the subsequent development of celiac disease by comparing subjects with celiac disease with matched controls (subjects without celiac disease).

-Antibiotic exposure was found to be associated with an increased risk of celiac disease, intestinal inflammation, and “potential” celiac disease (elevated Celiac antibodies on blood testing without any small intestinal changes seen on small bowel biopsy).

-Conclusion: The first study to show an association between antibiotic doses and the subsequent development of celiac disease. The authors postulate that an alteration of gut flora (ie. killing off of “good” bacteria) may play a role in the development of celiac disease.

4. “Markers of celiac disease and gluten sensitivity in children with autism.” Authors: Lau, N, et al. Published in PLOS One in June 2013.

-The researchers examined 37 children with autism and found that they had significantly higher levels of anti-gliadin IgG antibodies than children without autism (controls)

-Of the autistic children with anti-gliadin antibodies, most did not have either of the celiac genes (HLA-DQ2 and DQ8) and did not have other celiac antibodies (TTG IgA and IgG and DGP IgA and IgG). However, the majority of autistic children with anti-gliadin antibodies did have gastrointestinal symptoms.

-Conclusion: The anti-gliadin (gluten) immune response in autism involves a mechanism that is different from celiac disease.

5. “Colonic involvement in celiac disease and possible implications of the sigmoid mucosa involvement in its diagnosis.” Authors: Picarelli, A., et al. Published in the Journal of Clinical Immunology in July 2013.

-Researchers took samples of the colon (large intestine) of patients with Celiac Disease and evaluated the samples for celiac antibodies. They found that 75% of patients with Celiac Disease had anti-endomysial antibodies and 81% had anti-TTG antibodies in colonic tissue.

-Conclusion: The immune tissues of the large intestine are affected by Celiac Disease. In the future, large intestinal biopsies may be used in diagnosis.

Part 2 will be coming soon. Please feel free to comment and share articles related to celiac disease and/or non-celiac gluten sensitivity which you have found interesting as well. I would love to discuss.