Gluten Summit Speakers Series: What Did They Say?

For the second report (see here for the first) Micki Rose focuses on immunology with Dr Aristo Vojdani who, because he had so much interesting stuff to say, gets an article all to himself.

Dr Aristo Vojdani, clinical immunologist and microbiologist

Dr Vojdani’s focus in the field of immunology is on how environmental triggers like food peptides, toxic chemicals and infections are involved in complex diseases. He has published over 120 peer-reviewed articles over 40 years and, in fact, invented the IgG antibody test in 1985. He’s currently scientific advisor to Cyrex Labs, helping to develop better gluten testing.

An Immunology Lecture

Dr Vojdani started with a lesson on immunology. In effect, we have the innate, first cellular response where we don’t produce antibodies but release inflammatory chemicals like cytokines to fight any potential pathogens. It should stop there, but if the first response is overwhelmed and the body barriers are breached, we then start the second humoral response, creating antibodies which, in turn, sparks immunological cascades involving T cells, B cells, lymphocytes and other elements, which cause damage to the body and symptoms we can feel.

For IgE immediate reactions, he advises using a combination of skin prick plus IgE blood tests as he no longer feels that skin prick is reliable enough on its own. 

For delayed responses, even though he invented it, he cautioned against reliance on just IgG antibody testing because people can produce IgA and IgM instead of or as well as IgG, which I agree with wholeheartedly – I have offered that choice for over five years now.

He explained that the type of antibody can tell you a lot about the progress of sensitivity to a particular food.

We produce IgA first in the mucosal areas of the body including saliva and the gut lining. That IgA then sits on top of the lining and is ready to react as soon as it next sees some of the allergen, in this case gluten. Once the IgA is bound to the gluten, we should eliminate it via the bowel as usual. But, if this is happening a lot, it causes inflammation, which eventually is so damaging that we start to get hyper-permeability of the lining, mainly via the effect gluten has on zonulin, the gatekeeper molecule of the lining’s tight junctions. The more gluten reaction we have, the more zonulin we make and the more the tight junctions become permeable.

When the gluten and IgA bond gets through the barrier via the weakened tight junctions, the lymphocytes will start the process of making IgG or IgM antibodies over a week or so. Next, we make ‘complement’ and that attaches to the IgA/gluten bond and this is known as an immune complex, which are the most damaging and inflammatory molecules in our bodies; they’re like little bombs. Off they travel throughout the body and wherever these complexes of IgA, IgM or IgG get to, they will cause damage. That could be the joints, kidneys, brain, nerves, thyroid, adrenals; in fact, wherever your body weakness lies.

The Different Markers

So, by looking at the IgE antibody, we can see an immediate response to an allergen; at IgA, IgG and IgM, we see a delayed response. IgA specifically tells us it’s a mucosal and early antibody reaction and IgM/IgG tells us it’s now systemic. Vojdani reminds us that it can take up to ten years for symptoms or pathology in both coeliac and NCGS to show so it is wrong to ignore any positive antibodies.

I was delighted that he also reminded us that some people will not produce antibodies at all: some will have a cellular-mediated reaction, meaning lymphocytes will react to the food in the body and become activated, releasing cytokines and triggering the immunological cascades. Unless you look for those eg. using ALCAT type tests, you would miss them.

His reason for explaining all this, he said, was to show how daft it is that we just focus on IgE (and skin prick) responses in mainstream allergy medicine and on IgG for delayed sensitivity. He says unless we look at all of the antibodies, the cytokines, the cellular immune reactions, natural killer cell activity, T cell function, B cell function, the subpopulation of the lymphocytes eg Th1, Th2,Th3, Th17 and the follicular T helper cells, we are going to miss major components. In other words, unless all of that has been looked at – which is highly unlikely – the possibility of a gluten related disorder is still there. Gasp moment: I have never actually heard anyone come out and admit that before.

In terms of gluten specifically, the other advice he gives is - another gasp moment – that we shouldn’t just be looking for the anti-gliadin 33-mer peptide. What have I been saying now for 4 years?! It is well-known that 50% of coeliacs will test positive for gliadin antibodies, but 50% of them won’t. Vojdani says that error has led to many misdiagnoses. His new Cyrex 3 test has significantly widened the diagnostics, although I also suggest cellular testing like ALCAT for the very reasons he gave above. It’s not a perfect approach but it’s currently the best we have.

Vojdani’s recommendation is that we test as early as one year old for salivary IgA and IgM to the gluten peptides (Cyrex 1) and take action if they turn up positive. He quoted a paper published in 2011, where researchers found that, for 5,000 Italian children, this test was almost 100% accurate in diagnosing coeliac disease. Far easier and nicer than a biopsy!

The Importance of the B Cells

In terms of treatment, on a GFD, Vojdani advises that the gluten antibodies will remain elevated and detectable in the saliva or blood for at least 2-3 months and then, in an ideal exposure-free world, should start to reduce. But, after our first few exposures to gluten (and any other allergen), we make memory B cells, whose job it is to remember that antigen and sit, much like the earlier IgA, ready and primed to attack if it sees it again, even years later.

The problem is that those B cells are very quickly available in the body now instead of having to be built from scratch and, sadly, much more powerful, so if you have an exposure to your allergen, you will react much more strongly and need less and less each time to trigger it. He also cautions that they can eventually start to affect other body systems and organs. That explains why we get so hyper-sensitive where we weren’t before and why new symptoms start seemingly out of the blue.

It is for this reason that Vojdani doesn’t recommend rotation diets, a return to eating a positive food, or, importantly, a gluten challenge for diagnostics. The risks, particularly for gluten sensitives, he says, are just too high. The problem is that it is not just the outward symptoms we need to bear in mind, but the triggering and continuation of the hidden immune and inflammatory cascades internally.

In terms of monitoring, Dr Vojdani suggests regular testing of the antibodies, which should be lowering if the treatment is successful. Same goes for the cellular markers.

Finally, but importantly, he advises testing for common autoimmune antibodies, especially if the early salivary IgA and IgM test or Cyrex 3 is positive. It takes many years for pathology to actually develop so you can feel it, so testing early gives you a chance to stop any progression. He recommends re-testing the autoimmune antibodies after a year or so to check they are coming down. It takes time.

Suffice to say, I wandered around feeling depressed for days after this lecture. Dr Vojdani seems to be saying that once you have been exposed to the allergen, especially gluten, you can’t ever stop reacting to it and will do so at ever-decreasing amounts.

In my, happily, more positive view and having listened to the other speakers, it seems that the key is in stopping anything getting through that barrier. If the antigen can’t get in to the bloodstream, we don’t trigger the memory B cells as easily presumably and it is dealt with at IgA mucosal level. So, for me, anyway, I choose to believe that barrier healing and supporting IgA production is pretty vital!

Key Practical Messages:

• Diagnostically, look for as many indicators as you can especially the antibodies and cellular markers to confirm a gluten problem.
• Re-test after 3-4 months on a GFD to check they are reducing. In fact, this goes for any type of sensitivity.
• Check autoimmune antibodies so that you can identify anything early enough to stop it, then re-test regularly after 1-2 years to make sure they are coming down.
• Do not do rotation diets or gluten challenges because of the risk of doing further damage via molecular mimicry.
• Avoid exposure to your allergen even in tiny amounts for the same reason. • Exposure triggers a stronger and more symptomatically acute reaction to less and less each time

To read the introduction to the Gluten Summit, see here. Catch up with the mini-series 1, 2, 3, 4 and 5. And to read the conclusion see here

For more from me and on gluten related disorders generally, see my TrulyGlutenFree site.

July 2014

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