Celiac Disease

Celiac disease is known as "the great imitator" and is a potential underlying cause for pretty much any of the health issues that I discuss on this blog.  It should be no real surprise that it looks like I have it, and maybe Roo as well.  However, correctly identifying celiac via testing is complicated and unreliable, and following a celiac-GF lifestyle (not just diet) is extremely challenging, and not at all what "gluten-free" usually means.  While I have always done well on a "gluten-free" diet, I have never seemed to be sensitive to gluten to the degree that many people with celiac are.  Apparently this is deceiving.  Just as food allergies often seem vague and chronic until they are "unmasked", the celiac-level sensitivity to gluten that I have was not evident until I was able to get my gluten exposure WAY WAY down, effectively unmasking it.

The gluten theory of celiac disease was proposed by a dutch physician named Willem Dicke after World War II, and is the story we are all familiar with.  Gluten, a component of the grain seed that is found in wheat, barley, rye, and oats (sort of...long story), causes an autoimmune response in some people that damages the intestines, causing malabsorption and malnutrition, which in turn leads to many health problems.   This view of celiac is well summarized here on the Mayo Clinic site.  This view is also about 60 years old and in that 60 years there has been quite a lot of research done and the understanding of gluten and it's role in celiac has become much more complex.  It also turns out the before the gluten hypothesis, celiac was often treated with the Specific Carbohydrate Diet and success in treatment actually decreased with the change to the gluten-free diet.

What research has been showing is that there are many components that make up gluten that people have reactions to, as well as other components of wheat such as Wheat Germ Agglutinin (WGA).  Gluten is made up of glutenins and gliadins, of which there are many subtypes.  Celiac testing looks for one antibody to one form of gliadin.  There are many other autoimmune diseases that involve other antibodies to other forms, including Hashimoto's Thyroiditis, Cerebellar Ataxia, Narcolepsy, and Rheumatoid Arthritis.  It can be said that these are all "celiacs"...gluten-triggered autoimmune diseases.  This is explained very well by Kris Kresser in his article here:

"Wheat contains several different classes of proteins. Gliadins and glutenins are the two main components of the gluten fraction of the wheat seed. (They’re essential for giving bread the ability to rise properly during baking.) Within the gliadin class, there are four different epitopes (i.e. types): alpha-, beta-, gamma- and omega-gliadin. Wheat also contains agglutinins (proteins that bind to sugar) and prodynorphins (proteins involved with cellular communication). Once wheat is consumed, enzymes in the digestive tract called tissue transglutaminases (tTG) help to break down the wheat compound. In this process, additional proteins are formed, including deamidated gliadin and gliadorphins (aka gluteomorphins).

Here’s the crucial thing to understand: Celiac disease is characterized by an immune response to a specific epitope of gliadin (alpha-gliadin) and a specific type of transglutaminase (tTG-2). But we now know that people can (and do) react to several other components of wheat and gluten — including other epitopes of gliadin (beta, gamma, omega), glutenin, WGA and deamidated gliadin — as well as other types of transglutaminase, including type 3 (primarily found in the skin) and type 6 (primarily found in the brain).

This is a huge problem because conventional lab testing for CD and of gluten intolerance only screens for antibodies to alpha-gliadin and transglutaminase-2. If you’re reacting to any other fractions of the wheat protein (e.g., beta-gliadin, gamma-gliadin or omega-gliadin), or any other types of transglutaminase (e.g., type 3 or type 6), you’ll test negative for CD and gluten intolerance no matter how severely you’re reacting to wheat."

So, how prevalent is celiac disease?  Here Dr Joseph Murray, M.D of The Mayo Clinic presents findings from research that were published in 2009 showing an actual increase in the rate of celiac in the US population since 1950.  The researchers got ahold of blood samples that had been taken around 1950, and found that among those samples the rate of celiac was about 1 in 700.  For people tested now, of the same age as those from whom the old blood samples were taken, the rate was around 1 in 100.  They also tested people who were born around the same time as the people from whom the old samples were taken (born around 1930) and found that their current rate of celiac was almost as high, close to 1 in 100.  This suggests that celiac disease is at least 5 times more common now than it was in 1950.  Such a rapid and dramatic change in the rate of this disease indicates that something in the environment is playing a critical role.  The researchers followed up on the people from the old samples and found that those who had tested positive for celiac were about 4 times as likely to have died in the years since than those who were negative, suggesting that "silent celiac" (which refers to asymptomatic and undiagnosed celiac) are at significant risk from the disease.  Celiac has now become common enough that the risks associated with undiagnosed celiac are a significant public health issue.  He says to suspect celiac disease in patients with a family history of celiac disease, type 1 diabetes, premature osteoporosis, infertility, among other things.  He says we need to find out why celiac has become so much more common.

In an interview here, Dr Fasano gives some information that follows up on some of the questions about the increasing rate of Celiac Disease and what might be driving it.  His research found that the rate of Celiac Disease appears to be doubling every 15 years in North America.  He says that about one third of the population has a genetic predisposition to developing Celiac Disease, but for some reason most don't.  Of those how do, they can develop Celiac at any time in their lives.  While it is unclear exactly what triggers the disease to develop in some people there are some clues.  Babies who are fed gluten too early, such as between 2 and 4 months, have a much higher rate of the disease.  In Sweden in the 1970s, a formula was sold that contained gluten and the rate of celiac in people who received that formula is 9%.  Many researchers suggest that there is an optimal window in which to introduce gluten to children to minimize the risk of disease but no one is quite sure when that window occurs.  He speculates that this reflects the development of the immune system in young children which is influenced by the microbiota in the gut.

It has been found that people with Celiac have an altered gut flora but it is not known if this is a factor in causing Celiac or more of a result of having it.  Much of this interview is spent discussing the role of the gut flora in Celiac Disease, current research that is being done to figure out specifics such as  whether certain shifts in the gut microbiome precede Celiac Disease, and if so if this process can be changed in order to avoid developing Celiac.  He also wonders if changes in our diet, our increasing use of antibiotics over the past 50 years, some infections, or even the increase in travel during that time has played a part in altering our gut microbiome in such a way as to allow Celiac to develop more often.  He says he wouldn't be surprised if this becomes reality in the next 10 years.  However, unlike some doctors, Dr Fasano does not think that everyone is better off without gluten in their diets.  He has this to say:

"“We don’t digest gluten completely, which is unlike any other protein. The immune system seems to see the gluten as a component of bacteria and deploys weapons to attack it, and creates some collateral damage we call inflammation.

“But our bodies are engaging in this war all the time, and for the vast majority of us, there’s a controlled reaction, the enemies are defeated and nothing happens. Very few people eventually lose this battle and may develop celiac disease, gluten sensitivity or wheat allergy.

“So if you argue on that basis that we should all go gluten free, it’s like saying that we should all get rid of germs or bacteria. That’s ridiculous. Our bodies deal with bacteria all the time. We’re awash with them.”

More on the details of gluten composition and reactivity:

The classification and nomenclature of wheat gluten proteins: A reassessment

"It is concluded that the classical division into gliadins and glutenins is based on a secondary characteristic, the formation of interor intra- molecular disulphide bonds, rather than on homology of the primary amino acid sequences."

The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides

"We found that 50% of these patients do not respond to the α-GLIA peptide but to a diverse set of GLIA and glutenin (GLT) peptides, including 6 novel epitopes. Moreover, individual patients respond to distinct (combinations of) GLU peptides."

This is a post I wrote with research showing that many people with celiac disease react to the prolamins in corn independently from contamination with wheat gluten.

Wheat Starch, Gliadin, and the Gluten-Free Diet Some people consider non-protein containing wheat products to be gluten-free but this has not been established.

Immunochemical analysis of prolamins in gluten-free foods.  This is a thesis with a wealth of information about the structure of wheat gluten (also called prolamin) and celiac disease.

More about celiac:

Humoral Immunity Links Candida albicans Infection and Celiac Disease
"The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset. We investigated cross-immune reactivity between CeD and CI.

Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals."

Gluten and oxalate have been found to trigger an immune response in cells by activating a process in the cell called an inflammasome.  This effect is stronger in people with celiac disease than those who don't have it, but may also explain why some people with celiac require additional dietary changes beyond being gluten-free, and why some people have clear sensitivity to gluten but do not have celiac disease.  More on this here: 
Celiac and the Inflammasome: Reasons for the Relevance of Oxalate and Other Triggers

This article by Amy Myers, MD about gluten and celiac sums up the basics of the more current picture of celiac very well, and has a lot of good links in it.

This article has very updated information about the details of celiac disease, why testing may not show celiac, as well as information about other forms of gluten intolerance.

Detecting Celiac Disease in Your Patients is a more thorough and technical article directed at physicians that is a wealth if information about celiac disease.

Recent research has confirmed elevated levels of zonulin in patients with celiac disease.
You can read more about zonulin and how gluten leads to gut damage here (with a very helpful graphic).

This post has more about the common symptoms and diagnosis of celiac.

This post has detailed information about looking for celiac in intestinal biopsies, recent changes in diagnostic approaches based on biopsy, and information about mistakes that can lead to a diagnosis of celiac being missed.

Glyphosate, the active ingredient in the herbicide RoundUp, is suspected to be one cause of the dramatic increase in the prevalence of celiac disease in the twentieth century:
Glyphosate, pathways to modern diseases II:Celiac sprue and gluten intolerance

Information for following a Celiac-GF lifestyle:

American Celiac Disease Alliance
Gluten Free Society
Gluten Intolerance School is a site with recipes, information, videos and more.
Gluten Freedom: The Nation's Leading Expert Offers the Essential Guide to a Healthy, Gluten-Free Lifestyle
Going 100% Gluten-Free from The Liberated Kitchen

Confirmed Gluten-Free Drugs and Medications

New GF product standards have gone into effect as of August 5, 2014
What Does Gluten-Free Certification Actually Mean?
Gluten-Free Products and Warnings this page has a large collection of links to lists of gluten-free products, manyfacturer's sites, and more.
10 Unexpected Places Gluten Lurks
Going out to Eat
Celiac and meat glue
GF craft supplies
Corn mold toxins in the GF diet
This post from SCD Lifestyle discusses why the standard GF diet, which is high in processed foods with low nutrient quality, may not be the best healing diet for people with celiac.
The Gluten File

The possibility of medical treatment for celiac disease:

A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease
"In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease. "

Celiac and GF recipes and blogs:

The Patient Celiac is a blog by an MD with celiac herself
Elana's Pantry
GF Goddess
Gluten-Free Girl
Gluten is my bitch

Celiac and other diseases:

Systemic Autoimmune Disorders in Celiac Disease (a thorough medical review)
Celiac Disease Presenting as Autism
Wheat and Schizophrenia
Celiac can lead to calcifications (calcium stones) in the brain
A similar case presented in the scientific literature
Neurological Dysfunction in Coeliac Disease and Non-Coeliac Gluten Sensitivity.

More concerns about gluten and its effects:

Spectrum of gluten-related disorders: consensus on new nomenclature and classification
Interview with Wheat Belly author Dr William Davis (who is a cardiologist who has seen amazing changes in patients when they remove wheat from their diets).
Is it the gluten or is it the glyphosate (RoundUp)?
GM wheat may damage human genetics permanently
Modern wheat a "perfect, chronic poison" doctor says on CBS This Morning

For more advanced reading:

Structural Basis for Gluten Intolerance in Celiac Sprue

"A 33-mer peptide was identified that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in Celiac Sprue patients."

The Intestinal T Cell Response to α-Gliadin in Adult Celiac Disease Is Focused on a Single Deamidated Glutamine Targeted by Tissue Transglutaminase

"Here we have used recombinant antigens to demonstrate that the intestinal T cell response to α-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition."

VSL#3 probiotic preparation has the capacity to hydrolyze gliadin polypeptides responsible for Celiac Sprue probiotics and gluten intolerance

"The native structure and distribution of gliadin epitopes responsible for Celiac Sprue (CS) may be influenced by cereal food processing. This work was aimed at showing the capacity of probiotic VSL#3 to decrease the toxicity of wheat flour during long-time fermentation. VSL#3 (109 cfu/ml) hydrolyzed completely the α2-gliadin-derived epitopes 62–75 and 33-mer (750 ppm). Two-dimensional electrophoresis, immunological (R5 antibody) and mass spectrometry analyses showed an almost complete degradation of gliadins during long-time fermentation of wheat flour by VSL#3."