Tuesday 13 October 2015

The IgG antibody test: Vital for optimising nutrition? Part 2

Hello there, sorry I've taken a bit of time between posts but part 2 is finally here.

In part 1 of this post about IgG antibodies I aimed to separate the terms allergy and intolerance. I'm sorry if I laboured the point slightly but it is important to be certain of which is which.
If you do suspect you may have a food allergy then you MUST MUST MUST see a doctor! Get a proper diagnosis and then see a dietitian. Don't get all the info from some crackpot on the internet and spend your life unnecessarily avoiding certain foods. 

Here in part 2 I want to give you the information regarding IgG tests and let you decide if it is something that you think will optimise your diet or if it would be of no use at all. 
The post will consist of what we know about the IgG antibody, what the literature is saying on testing for food specific IgG antibodies and then finally I'll offer my thoughts on the topic.
Like I said in the previous post this will be as concise as possible, if you do want to delve deeper or discuss further please feel free to comment.
I didn't do an extensive literature review as I didn't want this post to be too long but I think I collected a good amount of evidence.

The IgG Antibody 

Antibodies are one of several ways that our immune system protects us. Antibodies are made by the B-cells and depending on the environment that this takes place in depends on the class of antibody. IgG is one class of antibody, it is actually the most abundant in humans and has several subtypes (numbered 1-4). Each class of antibody protects us in different ways. All the IgG subtypes are very good at a process called opsonisation, where the antibodies "tag" a pathogen and make it easier for other immune cells to kill it. IgG1 and IgG3 are both good at activating the complement system (a series of proteins that rid the body of pathogens).
Of course things don't always work as they should, remember the IgE antibody? Well that antibody is supposed to help us fight parasitic infection but as we know it also causes allergies. When things go wrong with the IgG antibody they can be involved in a condition called autoimmunity. When the immune system is functioning properly it is excellent as recognising self from non-self. In other words it can tell what cells are part of your body and what cells are foreign. This is why after a transplant the patient must take medication otherwise their immune system will attack the transplanted organ. With autoimmunity the immune system cannot tell the difference and starts to attack self! (1)
Coming back to the topic, the questions is can some reactions to food be mediated by the IgG antibody?

The Evidence 

I think one of the most frustrating things when reading about a topic on the internet is when the author writes "studies show" but then doesn't tell you which study so you can't go away and read it yourself and you just have to take the author at their word. I find this happens quite frequently in the health and fitness world. I even heard on one podcast that you should take written evidence "with a pinch of salt" and rely more on personal experience. Being diplomatic I'd say I strongly disagree with that statement so when writing this piece I wanted to make sure I provided references to studies that you could go and read and then form your own opinions. Although I do offer my opinion later I didn't want it to be just that alone.

Today a lot of health problems are attributed to the food we eat. We are becoming a lot more aware of the power of food, both good and bad. Some food related diseases are pretty clear cut, for example IgE mediated allergy, where as others are less so. When one study showed that the IgG4 antibody might induce histamine release (2) people began to question whether some food related symptoms that were not allergy could be mediated by this subtype of antibody. This idea began to look more credible when several studies demonstrated that removing foods that had high IgG levels improved symptoms in IBS patients (3-5). At the first glance this seems a strong argument for the need of the IgG test, however, we must be careful to not fall into the trap of confusing association with cause. Getting association mixed up with cause is a common problem when the headlines of a study are reported but not the actual details. Do we all remember the TV and Type II diabetes story that ran in the papers a few years back? Well it went like this, research found that the more time people sat in front of the TV the higher the prevalence of Type II diabetes. So our tabloid press announced that watching TV increased your risk of Type II diabetes. Of course people who thought about it for a second would realise that the TV doesn't increase the risk but because you are sat on your bum for many hours of the day does, the TV watching was just an association. If you spent the same amount of time staring at a wall your diabetes risk would probably be the same.
So back on topic, did the fact these IBS patients found that their symptoms improved after removing foods with high IgG levels show a causal relationship between high IgG and IBS symptoms or was it just an association? .
A study conducted in Norway wanted to look at whether the levels of IgG in the general (symptom free) population were different from those with IBS (6). There were 269 IBS subjects and 277 control subjects, diet was recorded through food frequency questionnaire and blood samples were collected and measured for specific IgG and IgG4. The results showed that there were no differences in levels of IgG/IgG4 between the populations and interestingly they found that lower levels of IgG specific to egg and beef were actually associated with an increased severity of symptoms. They also found that higher levels of IgG specific to chicken were associated with more severe symptoms. What you would expect to find is that the higher levels of IgG would be associated with the more severe symptoms regardless of food, obviously you would also expect to find higher IgG in the IBS population in general wouldn't you???
What the authors did discover was that the IBS group tended to view egg and beef as "problem" foods and avoided them, whereas they saw chicken as a "safe" food and ate it often.
This led the authors to conclude that IBS symptoms are unlikely to be mediated by the IgG antibody and that the presence of this antibody may merely reflect one's diet. In other words the more you eat something the higher the presence of IgG specific to that food. This is a point I will be returning to later.
An article in the journal of gastroenterology and hepatology which looked at alternative investigations for IBS concluded that they could not recommend exclusion diets based on high levels of IgG due to a lack of sufficient evidence and limited efficacy of such diets(7).
Wheat is often reported as a culprit for food related problems. Even without Coeliac disease or wheat allergy (not the same thing) people still report problems when consuming foods containing wheat proteins. A condition with the catchy name, Non-Coeliac Gluten Sensitivity (NCGS) has been gaining more attention over the last few years. Patients with NCGS will not be picked up with standard wheat allergy or Coeliac diagnostic testing but they still react when given food that contains wheat proteins.
A study in Italy wanted to look at the profile of a group of children with NCGS and compare them to a group of Coeliacs and a control group that had no problems with wheat/gluten (8). They found that 66% of the NCGS group had IgG antibodies specific to gliadin (part of gluten) compared to 86% in the coeliac group. However there was also 13% of the control who were found to have gliadin IgG. The authors concluded that as they suspected the only way to diagnose NCGS is with a food challenge and that any blood testing would not provide conclusive results.
Although it must be noted that this was only a small study (only 15 in each group) it does raise some interesting points. Firstly, most of the coeliac group showed IgG to gliadin, but if you cast your mind back to my first post I said that Coeliac is not a food intolerance/sensitivity. As the name suggests Coeliac is a disease and a complex one at that, it does involve antibodies against gluten and also some autoantibodies (antibodies against "self"). So it is important to remember that IgG in Coeliac disease does not prove the efficacy of IgG testing for all food intolerances. In fact, even when diagnosing Coeliac they tend to ignore the anti-gliadin antibodies (IgG) and look for the autoantibodies.
So what about the NCGS group? 66% of them had gliadin specific IgG. Now this makes me wonder if the IgG antibody was mediating their symptoms what was behind the other 44% of the group's symptoms? Remember this group were all confirmed to have reactions to gluten/wheat. The authors suggested that the innate immune system may play a part in NCGS. The innate immune system is a part of our immunity that is not involved in making antibodies. It was also suggested by the authors (and others) that NCGS may actually sit somewhere on the spectrum of Coeliac disease or may be a precursor to full on Coeliac. That could certainly explain the presence of gliadin IgG in just over half of the NCGS group.
So in summary I had found a few studies that reported positive results from avoiding high IgG foods but I hadn't found anything that demonstrates actual mediation of symptoms by this antibody.
In 2008 the European academy of allergy (EAACI) released a position paper on the use of testing for IgG4 against foods (9). A position paper is basically a "This is what we think" report and EAACI are one of the top associations when it comes to allergy (and intolerances).
Their conclusion was "Testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints".
Within the article they state that there is a lack of evidence that IgG4 causes any symptoms within humans. They state the one study that found IgG4 causing histamine release (2) was under very specific lab conditions that would be very unlikely within a human. They state that the procedure of testing is against a large spread of foods that often shows positive results without any corresponding symptoms. This is a point I will pick up in the next section. They also state that the presence of IgG4 indicates that the person has been repeatedly exposed to that food and that their immune system has recognised it as foreign but has also recognised that it is harmless. This statement mirrors what the authors of the Norwegian study concluded. They go on to state that the presence of IgG4 should not be thought of as a marker for hypersensitivity but as a marker of immunological tolerance.

So that is a brief look at what the literature is saying about IgG testing. In the following section I am going to add my opinions based on what I knew and what I have learned through my studies and reading the evidence.

My Thoughts 

Now even though I have spent most of this post trying to differentiate food allergy from food intolerance, for the next few paragraphs I will be comparing the testing protocols of each. It is important to rememebr that although allergy and intolerance are different, the blood testing part is essentially same. A sample of your blood is sent to a lab and the only difference is with allergy they look for IgE antibodies whereas with the other they look for IgG. I am not going to talk about the lab part of the test as it isn't the focus of this post and to be honest it isn't the issue. They say they detect the presence of specific IgG and that's exactly what the blood test does (although they don't say which particular sub-type of IgG they are looking at). It is the interpretation of those results and what comes before (or doesn't come before to be exact) that I have an issue with.
If we put the evidence to one side for a second and focus on the process as a whole. Even if IgG mediated food hypersensitivity was an established condition, the current method of diagnosis would be deeply flawed.
If you ask any professional who works in the field of food allergy what is the most important part of allergy diagnostic procedure they will almost certainly say "the patient history". This is an in-depth discussion with the patient, almost like an interview, where they discuss everything from their medical history, their work and social life, timing and type of symptoms. There are a few reasons for doing this, one is you can usually tell what is likely to be an allergy or not through a comprehensive history taking without having to resort to expensive and potentially dangerous testing. One allergist told me he often diagnoses from the history alone! Another reason is to avoid ambiguous blood test results and/or presence of IgE in an unexpected food. Lets say for example that you suspect you may have a peanut allergy. You ate a Snickers and then around half an hour later you noticed a rash appear and some swelling around the mouth. You go to the doctor and they take some blood and test you for every known allergen under the sun. When you get your results you find that yes you do have a very high IgE specific to peanut, at this point the doctor could be confident that symptoms + high IgE = peanut allergy. However, the doctor also notices that you have IgE to cow's milk. It's not as high as the peanut but its there. Does that mean you are also allergic to milk??? You tell the doctor that you have milk in tea and coffee and on your cereal but have never had any symptoms. But now you're not sure what to do, you're worried you may have a milk allergy too!!!
Now had the doctor taken a comprehensive history before the testing they would have known that you drank milk regularly and had no symptoms and therefore would not have even bothered asking the lab to test for milk IgE.
Before you think, "hang on a minute! The guy still had IgE to milk", it is important to remember that the presence of IgE alone is not diagnostic of clinical allergy. You must have a history of symptoms when consuming that particular food to be given the diagnosis of a food allergy. The presence of IgE alone is known as sensitisation. Basically your immune system has seen it and decided to make an IgE antibody specific to it. So would you recommend that the patient now avoids milk? The short answer is NO! IgE sensitisation without allergic symptoms indicates that you have become tolerant to that food and if you were to cease having it you may actually become allergic and may have a reaction when encountering that food in the future.This is why when people have immunotherapy they must continue eating the food regularly otherwise they may slip back into being allergic.
So coming back to the topic, a blood test without a patient history is at best unhelpful. Using my friend's client as an example, he was not asked to fill any kind of patient history, just a drop of blood was taken and he was tested against 200 (yes 200!!) foods. One of the many foods that came back as red, meaning high IgG, was egg (surprise surprise for a professional rugby player). I asked him if he had any problems eating egg, he told me not only does he eat loads of eggs without any problems he even owns his own chickens! This is a perfect example of how a blood test without a history can be unhelpful and potentially counter-productive. Had this guy then followed the advice that is given he would have avoided eggs (along with the other "red" foods) and would be without what was once a vital source of protein. The fact that he showed a high presence of IgG backs up what I found in the previous section where high IgG is more likely to be reflective of diet as opposed to food intolerance.
It must be noted that although none of the companies I looked at offered a pre test history some companies may offer it.
You could of course do your own patient history. A good method is to keep a food and symptom diary. Basically write down everything you eat and drink and record any symptoms you have and at what time they occurred. Then if you still want, you take the IgG test and match the foods with the symptoms to the test results. Or take this diary to a dietitian and they should be able to pick out the likely culprits and modify your diet accordingly.

So to conclude would I recommend the IgG antibody test? As things stand now with the lack of evidence and the problems with the diagnostic procedure I would have to say no. These tests are not cheap either and I would want to see some improvements in both the protocol and evidence before I'd consider parting with my cash. Of course there are many many people who have found that they have benefited greatly from avoiding their high IgG foods. But that brings me back to the question of association vs cause.
However that is just my opinion and I suggest you go and read the evidence and make your own mind up. I did consider doing an IgG test for this blog but due to price I decided not to, maybe if one of the companies comes across this post they'd offer me one?

I hope you found this post useful and if you want to discuss further please either comment below or tweet me at  @conditionforthe

References

1. Owen J, Punt J, Stranford S, Jones P. Kuby Immunology. Seventh ed: MacMillan Higher Education; 2013.
2. Parish WE. Short-Term anaphylactic IgG antibodies in human sera. Lancet 1970; 2: 591-592  
3. Atkinson W et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised control trial. Gut 2004; 53:1459-1464 
4. Zar S et al. Food specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastro 2005; 100: 1550-1557
5. Zar S et al. Food specific IgG4 antibody-guided exclusion diets improve symptoms and rectal compliance in irritable bowel syndrome. Scan J Gastro 2005; 40 :800-807
6. Ligaarden et al. IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population. BMC Gastro 2012; 12:166-174
7. Philpott H et al. Alternative investigations for irritable bowel syndrome. JGHF 2012; 28; 73-77
8. Francavilla R et al. Clinical, Serologic, and Histologic Features of Gluten Sensitivity
in Children. Journal of paediatrics 2014; 164: 463-467 
9. Stapel S et al. Testing for IgG4 against foods is not recommended as a diagnostic
tool: EAACI Task Force Report*. Allergy 2008; 63: 793-796