A Purposely Provocative Question: Is IgG and IgG4 Food Allergy Testing Unreliable?

[Scotty81]

Hello,

I've got a question about food allergy testing and I have seen conflicting opinions on this. The particular question I have concerns whether blood tests that measures IgG and IgG4 responses for foods are accurate. If you have an opinion, I would appreciate if you are aware of any scientific (i.e. reputable) studies that support your point of view.

Here are some links that propose the merits of IgG/IgG4 testing:

• IgG Food Antibodies from Genova Diagnostics
• Allergix® IgG4 Food Antibodies 90 – Serum
• Also, Dr. Neil Nathan, in his book "Healing is Possible" mentions in particular a type of blood testing called the ELISA/ACT test that Dr. Russell Jaffe developed. It seems that Dr. Jaffe started up a company called ELISA/ACT Biotechnologies LLC. I did see, in one posting that this company was reported to have mysteriously closed down about the 2005 timeframe, but they seem to be up and running from the looks of their website.

However, when doing an Internet search, it doesn't take long to find references that strongly suggest that the above methods yield too many false positives to be of diagnostic value. Other references even suggest that an IgG/IgG4 response to a food just means that one has eaten it many times, and that it is a body's normal physiological response to exposure, rather than an intolerance.

Here are some links that question the validity of IgG/IgG4 testing in general:

• A 2008 article in the journal, Allergy, titled "Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report". There's even a link to this article on Great Plains Laboratory website; they recommend IgG testing instead.
• A 2012 article in the journal, Allergy, Asthma & Clinical Immunology, titled CSACI Position statement on the testing of food-specific IgG
• There are many others that purport to discredit the above testing. But, just because one doesn't have any symptoms when eating a particular food doesn't mean that the food it actually good for that particular person. It could be doing damage to the GI system when consumed over a long time period.

I see that a similar question was raised in this forum back in 2011, but when reading it, I didn't come away with the feeling that I had a definitive answer to the original author's questions. I also realize that another way to test for food sensitivities is to do an elimination trial. But, other than testing empirically, I'm just trying to find if there is any validity to doing the test at all.

Thank you in advance for your insights.

Scotty81

 

[halcyon]

I've been curious about this as well but wasn't able to come up with much other than the noted criticism of the idea of IgG4 allergy testing. Admittedly I didn't dig very deep and kind of gave up on the subject.

I did have the IgE/IgG4 food allergy test done by HDRI. I was interested in this test (and ordered it before I learned of the criticisms) because I had suddenly developed a bunch of intolerance to foods (foods I never had a problem with before) after becoming ill with ME. Also, my IgG subclass test turned up elevated levels of IgG4 so it seemed like a possible link. The HDRI panel showed no IgE responses but did show an IgG4 response to a large number of foods, including a lot of the foods that I had suddenly become intolerant of. Yes, there were reactions to foods I eat often, but there were also foods I eat often with no reaction, and foods I haven't eaten in years with a reaction.

After learning of the criticisms I was discouraged and didn't bother trying to eliminate any of the reactive foods from my diet to see if it made any difference.

 

[Jonathan Edwards]

I think the 2012 CSACI report makes things fairly clear. As far as I know there is no evidence to link IgG levels with food intolerance and no immunological reason to think that there would be. The adverts for the tests you cite give no scientific basis or evidence and include a lot of pseudoscientific muddle.

These are not in fact 'responses' anyway. People with blood group O, which means that they lack the A and B antigens on their red cells, always have antibodies to A and B even though these are antigens on other people's blood cells that they have never met. The immune system is programmed to make antibodies to ANYTHING that is not self, in a random way. If you come into contact with something in the form of an invasive infection you do make more antibody to that something, but not generally if you eat it as food, because it is broken down before it gets into the tissues and the gut does not respond the same way as other tissues anyway.

So having IgG antibodies that bind a food does not mean a 'response' to the food. You may never have ever met it before. It just means that some of your antibodies react to that food - which is normal because it is non self. IgE is quite different and does relate to allergy.

I would start from the scientific position that there is absolutely no reason to think these tests mean anything. I would be interested to know if there is evidence that does in fact show some correlation with food intolerance but I suspect it does not exist.

 

[Scotty81]

@Jonathan Edwards,

Thank you for your timely reply to my question about the validity of IgG/IgG4 testing. I certainly agree with your statement that none of advertisements for the IgG tests provided any scientific references for their claims. In fact, I did a quick Internet search to find such articles and didn’t find any.

After I posted my question though, I checked the textbook titled “Laboratory Evaluations for Integrative and Functional Medicine, 2nd edition, by Lord and Bralley, for further information. I do know that these two authors work for Metrametrix (now Genova Diagnostics), so I am aware that I looked at a potentially biased source.

In their section on “Food-Specific IgG Antibody Testing”, the authors state that IgG/IgG4 antibody production does not necessarily reflect a reaction to the food itself, but rather is an indirect indicator of intestinal permeability (i.e. leaky gut). They also state that food should ordinarily be broken down into simpler substances that are non-allergic, which will not product IgG/IgG4 antibodies. (So, I actually think their statements are consistent with the ones you made above). The authors do say that if the gut is somewhat permeable however, then the partially “undigested” macromolecules can produce such a response. They also state that simply avoiding these foods is not the complete answer. Rather, they suggest avoiding the most “offending foods” for a time, take a supplemental protocol to heal the gut, and then slowly reintroduce the foods.

They cite 2 studies in this section:
Treatment of delayed food allergy based on specific immunoglobulin G RAST testing.
Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial.

I do see that there are concerns about the authors’ experimental design in the 2nd article, and therefore their subsequent conclusions about the relevancy of IgG/IgG4 antibody testing. However, I don’t think these concerns disprove the premise either.

In PubMed, there are further studies by other researchers that suggest IgG testing has merits. Two such studies are:

Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome.
The value of eliminating foods according to food-specific immunoglobulin G antibodies in irritable bowel syndrome with diarrhoea.

If, in fact, IgG/IgG4 antibodies are a response to foods that a person has eaten a lot of, then I wonder why more asymptomatic people don’t respond positively to such testing. (I wonder if this study has ever been done). Is it possible that the following hypothesis is valid? If the gut is normally tight, then chicken macromolecules will be converted into non-allergic compounds. Then, in the blood test, a person’s blood will say: “I’ve never seen that chicken before”, and not produce any or many antibodies. However, if a person’s gut is permeable, then a portion of the chicken will get through the intestinal wall before it is completely broken down into non-allergic components. Then, in the body, the blood will produce IgG/IgG4 antibodies to these macromolecules, consistent with your statement that the body is just producing normal antibodies to what it has been exposed to before. For the blood test, the blood will say “I know what this is; it is chicken”, and produce such antibodies. On the other hand, if the IgG/IgG4 antibody response is totally random, then so much for my hypothesis.

As an advocate for my daughter, who has CFS, FM and IBS among other issues, I am interested in whether any of the IgG/IgG4 tests are clinically relevant. My daughter has not had this testing though. In a stool test, she did have a very low total secretory IgA, (SIgA), which is a measure of “gut-associated lymphoid tissue” (GALT), and therefore another measure of intestinal permeability. So, that is why I’m thinking that a practitioner may recommend such testing in her future.

Thank you in advance for any follow up remarks you may have.

Regards,
Scotty81

 

[Sushi]

As an advocate for my daughter, who has CFS, FM and IBS among other issues, I am interested in whether any of the IgG/IgG4 tests are clinically relevant.

I can only respond from personal experience. I have had this testing and the foods that were flagged "for avoidance" were ones that I had a history of reacting too--i.e. I had regularly noticed that if I ate these foods my symptoms would exacerbate.

Sushi

 

[Jonathan Edwards]

None of the quoted studies look very convincing and certainly it does not look as if any firm evidence has been gathered here. The problem with this sort of popular theory is that someone is bound to test it not very well and only publish if they seem to get a positive result. I would have thought that a better way to look for food intolerance problems was simply to keep a diary of what foods are followed by problems and try cutting out what look like likely culprits for a period. What matters is what works rather than what turns up on a test. This sort of test now seems to be being sold to people widely without any reliable evidence and I would suspect it is a waste of money - and effort if you follow the test and get nowhere.

 

[Jonathan Edwards]

I can only respond from personal experience. I have had this testing and the foods that were flagged "for avoidance" were ones that I had a history of reacting too--i.e. I had regularly noticed that if I ate these foods my symptoms would exacerbate.

Sushi

Then I guess you didn't need the tests, Sushi?!

 

[Sherlock]

What about the idea that, with bad leaky gut, large peptides can get into circulation and cause an IgG response to almost any food?

...

Is it possible that the following hypothesis is valid? If the gut is normally tight, then chicken macromolecules will be converted into non-allergic compounds. Then, in the blood test, a person’s blood will say: “I’ve never seen that chicken before”, and not produce any or many antibodies. However, if a person’s gut is permeable, then a portion of the chicken will get through the intestinal wall before it is completely broken down into non-allergic components

As far as I'm concerned, that is perfectly valid.

I had pondered for years if I was allergic to whey. It seemed that sometimes I was, sometimes I wasn't. I compared to skim or full fat milk, to casein, to yogurt, etc. Finally, I realized that I did have a reaction to whey only when I had leaky gut -- like a conditional sensitivity, with dark eye circles and other symptoms. I never had such a conditional problem with anything other than whey, btw. Certainly not atopy.

You would probably find that out in the world this idea relating to permeability is generally accepted. It also explains why any food elimination that you try might give inconsistent results. But still the testing is probably a waste of money.


You would also find that out in the world, with e.g. eosinophilic disorders of the digestive tract, that standard allergy patch or prick testing is commonly negative to foods that are known problem foods. The only advantage that I see in testing is in possibly pointing to possible problem foods once you've eliminated the usual top 6 foods and found no relief from symptoms... dairy eggs gluten seafood nuts soy Burt even then the testing is probably wasted.

 

[Sushi]

Then I guess you didn't need the tests, Sushi?!

Nope, for me they were just a confirmation. I have had the habit for years of tracking the variables that might be associated with an increase in symptoms so I had naturally been tracking food too. The test might be helpful for someone who wasn't in the habit of doing this though.

Sushi

 

[Forbin]

Yes, but what if one were "allergic" to a food that was so ubiquitous in the food supply that it would otherwise be nearly impossible to tease out what you were having a bad reaction to? I'm thinking of corn specifically. Corn (in one form or another) is to be found in a vast number of processed foods, but unless you actually were to note a reaction to eating unprocessed corn, you might search in vain to figure out what it was among all the ingredients of processed foods that you were sensitive to.

 

[Valentijn]

Then I guess you didn't need the tests, Sushi?!

I did. I got the blood drawn for my first test in the Netherlands shortly before traveling to the US to visit family. I already knew I was reacting to some foods (primary symptoms were itching in the gut area and widespread swelling), but started getting a much more intense reaction shortly after arriving in the US. After a few days it was bad enough that having my legs resting on a soft couch was constantly painful because of pressure.

We went to the urgent care weekend clinic, where the doctor referred to my swelling as "non-pitting soft-tissue swelling" but the tests he ordered came back pretty normal a few hours later, aside from elevated ESR and traces of blood in my urine, both of which I've had consistently since getting ME. I emailed the Dutch lab to ask if any of my results were in because I was having some worrying problems, and it turned out that one of the strongest positive results was for cranberries.

Sure enough, my mother had been feeding me wonderful salads with dried cranberries as one of the ingredients. Within a day or so of avoiding those, the swelling went down to my "normal" levels. I'm an American from the Pacific Northwest (cranberry country!) and have been eating cranberries at least yearly since I was little kid, as it's a traditional Thanksgiving food, and I was also drinking cranberry juice on a regular basis. And suddenly I couldn't eat it anymore without getting visible full-body swelling.

Not all of my intolerances showed up on the test, but just the ones where I tend to get different sorts of symptoms after eating those foods were missing. Another test from a different lab a couple years later turned up the same results, though showed milder reactions for the same foods.

So my personal experience is that it was pretty accurate and extremely helpful. Even if there isn't much science behind it yet, at least the cost is reasonable.

 

[jack blogs]

I did. I got the blood drawn for my first test in the Netherlands shortly before traveling to the US to visit family. I already knew I was reacting to some foods (primary symptoms were itching in the gut area and widespread swelling), but started getting a much more intense reaction shortly after arriving in the US. After a few days it was bad enough that having my legs resting on a soft couch was constantly painful because of pressure.

We went to the urgent care weekend clinic, where the doctor referred to my swelling as "non-pitting soft-tissue swelling" but the tests he ordered came back pretty normal a few hours later, aside from elevated ESR and traces of blood in my urine, both of which I've had consistently since getting ME. I emailed the Dutch lab to ask if any of my results were in because I was having some worrying problems, and it turned out that one of the strongest positive results was for cranberries.

Sure enough, my mother had been feeding me wonderful salads with dried cranberries as one of the ingredients. Within a day or so of avoiding those, the swelling went down to my "normal" levels. I'm an American from the Pacific Northwest (cranberry country!) and have been eating cranberries at least yearly since I was little kid, as it's a traditional Thanksgiving food, and I was also drinking cranberry juice on a regular basis. And suddenly I couldn't eat it anymore without getting visible full-body swelling.

Not all of my intolerances showed up on the test, but just the ones where I tend to get different sorts of symptoms after eating those foods were missing. Another test from a different lab a couple years later turned up the same results, though showed milder reactions for the same foods.

So my personal experience is that it was pretty accurate and extremely helpful. Even if there isn't much science behind it yet, at least the cost is reasonable.

Thanks for sharing, was this Igg or igg4 testing?

 

[anciendaze]

You might check on genetic variants in genes connected with Igg4. Here's a patient who went through all manner of false diagnoses before discovering this allele was in her family. Expecting a single chemical tripwire for diagnosis is unrealistic.

As for the unreliable tests, I could say the same about most other tests for autoimmune diseases. Things typically identified with allergies are classically connected with IG E. Mast cells alone release some 200 different biochemicals, so there is plenty of room for pathological interactions that don't count as allergies. Considering "self versus other" there is nothing preventing the body from generating autoimmune responses; the immune cells involved are created, then fight it out with other immune cells to determine which count as "self". You can find some level of autoantibodies in everyone.

Microbial populations on mucous membranes outnumber human cells, yet attacking all of them as "other" would lead to chronic inflammation, immune exhaustion and death. The exact mechanism for triggering specific immune responses in the liminal region between microbes and the interior of the body remains unclear. There is no barrier between the body's immune defenses and these microbes; there can't be when molecules as small as amino acids, glucose and oxygen have to pass back and forth. I'm afraid the whole subject of autoimmune disease is filled with social constructs made by doctors for doctors. A patient without such convenient clinical signs as the pathognomonic rash of systemic lupus erythromatosus is likely to get different diagnoses from different doctors. Some of these will say "It's never lupus", to quote the esteemed Dr. House in one episode.

This state of the art is far from satisfactory.

 

[Learner1]

Detecting food intolerances/allergies is not a perfect science. The tests may provide valuable clues, but aren't perfect.

I did the Genova Diagnostics Elisa test. It showed that reacted to 43 foods, many of which are regularly, including things no one is allergic to, like pears. They suggested a rotation diet, which I tried, but it drove me crazy - with tomatoes one day, cucumbers the next, lettuce the next, and so on....I'm a flexible and creative cook, but it was ridiculous.

Ffinally, I went to the Bastyr clinic and saw a doctor who specializes in allergies. He said, I know you've been tested, but we've been getting good results with this one. the US BioTek IgE/IgG/IgA test.

My results showed huge IgG reactions to cow and goat milk, including casein and chicken eggs, as well as reactions to pineapple and oysters. No IgE or IgA. I do violently react to eggs and cow and goat milk products, even hidden in foods, where I didn't used to before I cleaned up my diet.

The test didn't show corn, which I break out in hives with or wheat, which I've had antigliadin antibodies. And I seem to be able to eat pineapple... I've seen a lot of people show up with it on tests but still became to eat it...and have concluded theres something odd about testing pineapple.

One of my children did an elimination diet and now avoids wheat, cow and goat milk, eggs, and came sugar. (She did this before I was tested.)

My other child did the US BioTek test and showed IgE reactions to oranges, rice, and eggplant, which she reacts to, and IgG reactions to milk and eggs.

I know what the allergy doctors associations say, but we've found testing to be highly useful at pinpointing what we have a problem with, if not a perfect science.

As for IgG, seems to me, if your immune system reacts to it, you've got a problem... reducing inflammation and having a happy immune system is a good thing. So is fixing a leaky gut, so that foods aren't getting into your bloodstream for your immune system to see them.

Also, we've found the "Food Intolerance Bible" by Anthony Haynes to be a helpful resource.