Wednesday, November 5, 2014

Whose idea was it to re-classify coelic disease (gluten intolerance) as an autoimmune condition? Which special interests allowed that bonkers idea to become received wisdom - and why?

A typical description of coeliac/celiac disease, stating it to be an "automimmune condition". Fact?  Or a misguided PR attempt to exonerate wheat and some other cereal proteins? (" It's not the bread that 's at fault, dear, it's the way your body reacts to it.")

Suppose I were claim that HIV/AIDS was not primarily a viral disease, that the fault was really down to you and your over-reactive immune system. 

You’d say I was mad, and rightly so.

But something dangerously close to that thinking is now being touted as “received wisdom” as I discovered this morning, scanning the new headlines on AOL (they flash across my email inbox), and then going to Google and wiki to have my worst fears confirmed.

Yes, it's  being claimed this morning on AOL that gluten intolerance, aka coeliac disease, is an "autoimmune" condition.  In other words, a condition that develops when the body's immune system goes awry and  turns on itself, regarding its own proteins etc as though "foreign invaders" that have to be intercepted and neutralized.

But gluten, a major class of proteins in wheat (primarily) and other cereals IS foreign. The body does not make its own gluten. So how come coeliac disease is now being classified as an autoimmune condition, as if it were essentially no different from Type 1 (insulin-dependent) diabetes?

Here's a blow-by-blow account in pictures:

See AOL news item on right: "Gluten. Coeliac Disease. Know the Facts. This autoimmune condition is more common than some think"
 Autoimmune? Coeliac disease? Gluten intolerance?  Since when has coeliac disease been an autoimmune condition, given it's triggered by a foreign antigen?

Here's a close up of the article.
Surely the journalist go it wrong?  But lo and behold, wikipedia says coeliac disease is an autoimmune condition (words inside my yellow rectangle). On what basis can a disease triggered by a foreign protein be considered 'autoimmune' ( a reaction to one's own proteins etc)?

Here's what wiki has to say under "autoimmune disease".

 It says (exact words): Autoimmune diseases arise from an abnormal immune response of the body against substances and tissues normally present in the body .This may be restricted to certain organs or ??? a particular tissue in different places".

"...normally present in the body?". But there are substances normally present in most people's bodies that are of foreign origin, like the common components of diets. So what earthly use is this wiki definition of "autoimmunity" (auto- meaning self) given it fails to differentiate between one's own and foreign proteins? Already it's becoming clear how coeliac disease could come to  be misclassified given that autoimmune disease has been sloppily defined to mean pretty well anything.

So has coeliac disease been added to wiki's list of "autoimmune diseases"? Answer- YES!

There it is in the list of autoimmune diseases, between Castleman's disease and Chagas disease.

Note is says "Accepted" (as an autoimmune disease). By whom, and on what authority? Three references are given, numbers 15,16 and 17 in blue.

Here are the three references that we are told back the classification of coeliac disease as an autoimmune condition.

Ref 15: Uninformative title. No authors or date.

Ref 16: Meize-Grochowski, R. (2005)  "Celiac disease:a multisystem autoimmune disorder."

Is that in a recognized journal of immunology? No, it's in "Gastroenterol.Nurs", which appears to be primarily concerned with patient care, not fundamental science.

Ref 17:  Sollid,L.M., Jabri,B (2005) "Is celiac disease an autoimmune disorder?"  Current opinion in Immunology.

So it's not stating categorically that coeliac disease is autoimmune. It's asking if it's autoimmune. So what's it doing in a list of 3 references that are supposed to be supporting a claim that the classification is "accepted" when it's merely being proposed?

There is something profoundly not right here. I shall now have to try and find what those 3 papers say, but already have a strong suspicion that coeliac disease has been misclassified. Why? Who might benefit from that, i.e a kind of whitewash?  "Don't blame us, it's your own over-reactive immune system that's at fault"

So what's this blogger's beef you may ask. Does it really matter what label you attach to coeliac disease - autoimmune condition or food allergy (I believe it's the latter). Either way the individual has to eliminate gluten as much as possible from the diet.

But that's the whole point. Eliminate the foreign substance to which you may  be sensitive, and chances are your gut epithelium will start to recover and your the symptoms will subside. So yes, you were ALLERGIC to wheat, and don't let anyone tell you different, or try to blind you with immunological mumbo jumbo.

So why attempt to whitewash cereal gluten, making out the fault is with the individual's immune system, that they are somehow "faulty" humans. No, they are not. They have simply inherited a set of genes from mankind's earlier caveman history that had not yet acquired tolerance to a particular source of protein that was becoming a major food source with the arrival of agriculture.

So why did early man probably react in far greater numbers to wheat and other proteins (as a sizeable proportion of the Irish still do, with potato having been their staple for centuries, not wheat)?

Answer: because wheat grains and their food stores are that species means of sustaining the next generation of plants. They did NOT evolve to be a staple of human diet. Indeed, one might hypothesise that wheat gluten evolved not only as a handy way of storing protein, but as a means of making its predators ill and less likely to reproduce. (OK. it's a long shot, but I may have more to say on that score at the biological and molecular level in future posting).

OK. let's cut to the chase, and see how science is being doctored to foster cosy illusions re health and diet. The narrative runs as follows. Bread and other cereals are 'friendly' - the staff of life etc etc. The 'gluten intolerance' thing must not be allowed to distract from that entirely fanciful view of human nutrition. So if you are one of the unfortunate people who is intolerant to gluten, for whom it's in fact a chronic poison, wrecking the lining of your gut, then it's because there's something wrong with you. Your reacting against gluten is essentially no different from your reacting against your own body tissues - i.e. an autoimmune condition, because cereal protein is so wonderfully essential a part of our diet, and has been for millennia that it's essentially ONE OF US. So we'll not only declare you to be a freak and evolutionary cripple for being gluten intolerant. We'll even doctor the definition of autoimmune disease, replacing an immunological reaction against your own tissues with a reaction to anything that is a "normal part of your tissues", handily making out that anything most folk can tolerate in their diet must be considered essentially no different in immunologocal terms from human tissue.

All of this needless to say is a shameless travesty of reality. We are born with a unique mix of genes that represents a particular and probably unique blend of inherited components that have been passed on because each confers some survival advantage, long enough to be passed on to progeny. What one can't be certain of  is whether tha particualr MIX one has inherited is ideal for the life circumstances in which one finds oneself  with certain foods readily available, others less so.

If there's a particular item of diet that you react against - be it gluten or something else - then it's not a "fault" in your metabolism or immune system. It's simply that you are one variant of "healthy" but ill-adapted to a  particualr foodstuff your body still regards as "foreign" and which tries to reject at the cellular and molecular level. In short you are allergic to that food. Attempts to reclassify coeliac disease as an autoimmine condition are simply a ploy to get the term "wheat allergy" out the public domain. It's a PR job, pure and simple, one that is designed to protect the image of cereals as ideal, made-for-man food whose reputation must not be sullied by the 1% who show intolerance.

Coeliac disease is NOT an autoimmune condition, any more than an anaphylactic reaction to a bee or wasp sting. It's your body reacting, or over-reacting- to a foreign protein to which your immune system for whatever reason is on constant high alert. Repeat: you are a variant of "normal", part of a normal bell-shaped distribution curve.

It's time to put the clock back and start re-educating the public on the realities of diet and immune response. The first priority should  for wiki to exclude coeliac disease from its list of autoimmune conditions. Hopefully journalists will get the message too, instead of uncritically transmitting industry-friendly narratives.

Late addition

Have been googling 'coeliac disease autoimmune' and have come up with the following.

First: an abstract of one of the three papers listed above:

Curr Opin Immunol. 2005 Dec;17(6):595-600. Epub 2005 Oct 7.

Is celiac disease an autoimmune disorder?


Celiac disease, which results from an immune reaction to ingested cereal gluten proteins, has several autoimmune features. In particular, celiac disease patients produce highly disease specific IgA and IgG autoantibodies to tissue transglutaminase when they are on a gluten-containing diet, and they have small intestinal intraepithelial lymphocytes which can mediate direct cytotoxicity of enterocytes expressing MIC molecules in an antigen non-specific manner. Similar to typical autoimmune disorders, celiac disease has a multifactorial aetiology with complex genetics, and several autoimmune diseases are commonly presented by patients with celiac disease. Much has been learned about the immunology of celiac disease in recent years, and there is overwhelming evidence that the immune response to gluten is central to the pathogenesis. In light of this, the many autoimmune phenomena associated with celiac disease are thought-provoking, and they challenge us to rethink the boundaries between autoimmunity and immunopathology.

My response: will be added tomorrow.

Second:  This passage from this link  really says it all and frankly astonishes me for its failure to spot the obvious - namely that it's a specific FOREIGN protein that is being 'mistakenly' recognized IN THE FIRST INSTANCE as the enemy in the first instance.The subsequent immune response is a secondary SYMPTOM, not a primary cause.

Cut-and-paste from the article (my highlighting):

What is coeliac disease?

Coeliac disease is a condition that causes inflammation in the lining of the small intestine (part of the gut).

Coeliac disease is not a food allergy or a food intolerance. It is an autoimmune disease. The immune system makes white blood cells (lymphocytes) and antibodies to protect against foreign objects such as bacteria, viruses, and other germs. In an autoimmune disease, the immune system mistakes part or parts of the body as foreign. Other autoimmune diseases include type 1 diabetes, rheumatoid arthritis and some thyroid disorders.
The cause is a sensitivity to gluten. Gluten occurs in common foods including wheat, barley, and rye, and any foods made from these such as bread, pasta and biscuits. Some people with coeliac disease are also sensitive to oats.

People with coeliac disease make antibodies against gluten. Antibodies are proteins in the immune system that normally attack bacteria, viruses, and other germs. In effect, the gut mistakes gluten to be harmful, and reacts against it as if it were fighting off a germ. These antibodies lead to inflammation developing in the lining of the small intestine.

Coeliac disease can develop in babies. Older children or adults who have not previously had problems may also become gluten-sensitive at some point in their life and develop coeliac disease. It is not known why the immune system of some people becomes sensitised to gluten.

Here's a third splendid-looking feature that I've only had time to skim briefly, but already it's clear that the lady's focus and thinking chimes closely with my own. It's the gluten that is the culprit, and the primary reason is to do with its specific amino acids sequences, i.e.  the order in which they are linked that prevents them being digested down to individual  amino acids. The digestion stops at the peptide stage, and its those peptides that get absorbed and trigger the immune response.

Celiac Disease: How gluten invades and sets up an auto-immune reaction

Julianne Taylor, RN
Primal Docs
Mon, 23 Sep 2013 09:29 CEST

Discussion to  follow. Comments/criticism invited.

Thursday 6th October

I think I know how the decision to re-classify coeliac disease as an autoimmune disease was arrived at. But there are two elements to it. One is to do with mechanism, inasmuch as there is a secondary autoimmune phase that gives rise to the chronic inflammation and malabsorption. But there's a deeper philosophical one that I strongly suspect to represent an aversion on the part of the medical fraternity towards a key plank of modern biology - the one that supports a host of otherwise inexplicable phenomena

Here's a clue to the shape of the hole that exists in the medical mindset, at least at GP level.

 D for ?  

Part of what's to follow is an appreciation of the natural life cycle of wheat and other cereals, not the modern strains, but the kinds that existed as wild grasses prior to agriculture. Yes, the D word will feature more and more here.

In passing,  it came as a pleasant surprise on reading the wiki entry on "Wheat" to come across this section which, to my mind, is spot on re the TOXICOLOGY, a word I use not lightly, with no mention of the A word.

Yes. wheat did not evolve to serve human nutritional needs. Wheat evolved to serve the interests of wheat. D for ?

Health concerns

Main article: Gluten sensitivity
Several screening studies in Europe, South America, Australasia, and the USA suggest that approximately 0.5–1% of these populations may have undetected coeliac disease.[54] Coeliac (also written as celiac) disease is a condition that is caused by an adverse immune system reaction to gliadin, a gluten protein found in wheat (and similar grains of the tribe Triticeae which includes other species such as barley and rye). Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the bowel tissue, causing an inflammatory reaction. That leads to flattening of the lining of the small intestine, which interferes with the absorption of nutrients. The only effective treatment is a lifelong gluten-free diet.
The estimate for people in the United States is between 0.5 and 1.0 percent of the population.[55][56][57]
While gluten sensitivity is caused by a reaction to wheat proteins, it is not the same as a wheat allergy.

More later, once I've had a chance to read that Julianne Taylor paper.


Thibault Heimburger said...

Hello Colin,

The coelic disease (CD) has not been "reclassified" as a autoimmune disorder. It has been recognized as a autoimmune disorder since many years.

"Autoimmune" means that the immune system reacts against antigens that are normally present in the body.
This is true for the CD, in which the immune system reacts against the transglutaminase enzyme which is present in the bowels (and in other organs). It also reacts against the endomysium (connective tissue).
Gliadine is the "starter".

As a general rule, an autoimmune disorder implies:
- A genetic HLA predisposition:95% of the CD patients are HLA DQ2 or DQ8 (20-30% in the general population)
- T Lymphocytes and/or B lymphocytes abnormal reaction. This is true for CD which is primarily a T lymphocyte (HLA mediated) reaction against the gliadine/transglutaminase molecular complex. The T activated lymphocytes then "produce" B lymphocytes which produce the antitransglutaminase and anti-endomysium antibodies. Both T and B lymphocytes are involved in the lesions and then the symptoms of CD

Things are much more complex.

It seems to me that you don't understand truly the concept of autoimmune disease.

sciencebod said...

Hello again Thibault

(That's Thibault Heimburger MD for then information of others reading this).

I don't dispute for one moment that CD presents as if it were an autoimmune disease, where the body ceases to discriminate between self and non-self. But gliadins are not just a "starter". Take them away from the diet and the gut begins to recover. So I would describe CD as a wheat allergy, albeit one in which there's a secondary auto-immune phase that produces the major damage.

I note what you say about genetic predisposition, and that makes it easier to think of the condition as being something wrong with the patient. But people differ in all kinds of ways that may predispose them to opportunist pathogens etc. But as a biochemist by training (arguably more biologist than chemist) I see things from a Darwinian standpoint. That reaction to gluten is no biological accident, wheat etc are not as benign as some would have us belief ("the staff of life" etc) and there were probably reactions on a far greater scale and severity when man first began growing and consuming cereals in quantity.

I see it in terms of biological warfare. Wheat gluten with its peculiar amino acid sequences (high proline etc) giving its peptides unusual properties (resistance to enzymic digestion etc)did not just evolve to be a good storage protein. It evolved to produce gut problems in animals and later people who tried to gorge on the grains before they had time to germinate. The mechanism of action is fearsome, exploiting a weakness in our immune systems, some genetically more vulnerable than others, that makes us react against ourselves. Take the gluten away, and hey presto one's on the road to recovery.

Autoimmune? Not in the same way as arthritis etc where as I recall there is no obvious external provoking factor, certainly not a life form defending itself against predation.

Having worked for several years in UK hospitals and medical schools, I've developed a hunch that the conservative medical profession has little time for Darwinian biology (understandably, given it's a bleak subject in the context of preventing or curing disease). But the reality is that we live in a dangerous world, as the Ebola epidemic is proving.

So why not tell CD sufferers they are maladapted to a food that was once potentially toxic to most of our ancestors, and they have to concentrate on eliminating it from their diet, at least till a selective immunosuppressant is discovered. How does it help the patient to be told they are suffering from an "autoimmune disease" when there are presently no drugs to treat it, when prevention is then only viable option - and WORKS!

sciencebod said...

Here's a paper that would seem to me to point the finger of blame firmly at gluten - a failure of the gliadin to be completely digested, accompanied by absorption of the peptide fragment that acts as a potent antigen.

Recent studies on -gliadin have uncovered the molecular explanation of why a 33 amino-acid stretch of -gliadin possesses such immunodominant characteristics. Shan et al demonstrated that this portion of gliadin is apparently extremely resistant to intestinal digestion leaving such regions available for T-cell recognition and activation of pathogenic T cell. Remarkably, all the patients tested responded to this portion of -gliadin.36 It was demonstrated that this 'digestion-resistant' section of -gliadin has a high affinity for tTG deamidation and the up to 6 T-cell epitopes, including the ones previously described by Sollid's group.37

Gene Therapy (2003) 10, 835–843. doi:10.1038/
Celiac Disease: a model autoimmune disease with gene therapy applications
M Londei1, S Quaratino2 and L Maiuri1,3

There's another way of discriminating between gluten toxicity, with an autoimmune component ("autoimmune disease" being an unhelpful misnomer. That is to look at the prevalence of CD in animal models, and see whether or not there are common genetic and immunological factors between human beings and animals.

A brief session with search engines shows there is indeed a rapidly expanding literature on animals models. One paper describes how CD mice were produced by raising several generations of mice on a gluten-free diet and then provoking a CD response with gluten.

I shall report back in due course once I've developed a feel for the literature.

sciencebod said...

Come to think of it - in summer we walk past fields of ripening wheat and other cereals, and by the time the combine harvesters arrive that will be almost fully mature grain with its store of starch, protein (including that gluten etc), vitamins, minerals etc. SWo why is it one only sees an occasional mouse, vole or other rodent? One would surely expect an explosion in their numbers to take advantage of the feast on offer. Could it be that wheat etc is toxic to rodents - and they know it?

I say that CD should be seen as the tip of an iceberg of cereal grain toxicity, and that the mechanism of toxicity, arrived at through chance via evolution, is a derangement of the immune system such that the animal or person ceases to distinguish between self and non-self. The progressive damage to the gut with loss of villi etc gradually weakens the animal which can then no longer forage for food so well, and then more cereal grains survive to then germinate and make new progeny. (I could rfine this by mentioning the rodents' tendency to collect grains and store them away in nooks and crannies but will leave that for now).

Instead of trying to fix our immune systems to make them more resistant to gluten, ought we not to concentrate on wheat breeding programmes that make the gluten less damaging to our guts and immune systems?