interpreting bloodwork / what's it mean that total IgA is low?
 

My daughter was diagnosed w/ gluten sensitivity several wks ago via stool test, so I asked my dr. if I could have bloodwork to test for Celiac's.

Results:
Deamidated gliadin ABS, IgA 1.7 (normal 1-10)
Deamidated gliadin ABS, IgG 0.07 (normal 1-10)
t-transglutaminase, IgA 1 (normal 0-3, weak positive 4-10, positive >10)
t-transglutaminase, IgG 1 (normal 0-5, weak positive 6-9, positive >9)
endomysial antibody, IgA negative
Immunoglobulin A, QN, serum 60 L (normal for > 19 yrs is 70-400)

My dr read this as meaning I'm fine, while acknowledging this isn't her area of expertise. But a naturopath dr I asked about it said that b/c my IgA is low overall, the rest of the test results are invalid, unhelpful. But he didn't have much more to say than that.

Can someone point me to a good source of info to explain what all these tests are about, particularly the last one? What's next? Would IgA stool testing be similarly invalid b/c of lack of IgA? Do I need to do something about the lack of IgA? What problems could I have b/c my IgA is low? Any info helpful. Thanks.

if you dont have a sufficient amount of IgA, then you arent going to mount a defense on that front.....so the all the IgA based tests will be skewed. also, you need the old, not deaminated, tests done....and the IgG tests done....
that being said, if your daughter lives with you, why not go gluten free with her?

Edit to say: What she said...lol. Here is the LONG version of the answer.

What they are looking for is a condition called Selective IgA Deficiency. There are sort of two categories of this.

Total IgA deficiency is of the most concern, and is defined (from what I have read) as an IgA level less than 7. If someone has total IgA deficiency they can run into problems if ever needing a blood transfusion.

Below range IgA is also considered being "IgA deficient", and may make one more prone to general illness, food sensitivity, and such, but isn't considered as big of a deal. Most often, people never even find out they are low in IgA.

My daughter, like you, falls just below normal range. She does have more than her fair share of common colds, throat infections, sinus infections, urinary tract infections, etc. As a child, she couldn't get a cold without it "turning" into a sinus infection, ear infection, etc. Have you been plagued by increased general illness or infections?

How is it related to celiac disease?

There is a higher prevalnce of IgA deficiency in those with celiac disease than in the general public, and there is a higher prevalence of celiac disease in those with IgA deficiency. Increased association both ways.

The bigger issue in diagnostic testing for celiac disease is that any of the IgA tests used for celiac screening are not reliable measures in people who are IgA deficient. If you don't make IgA, you can't show IgA on these tests. So, then it is important to also test the IgG versions of the test... and it looks like they have done that.

Good for your doctor for checking Total IgA and running the IgG versions of the tests. That is a loophole sometimes left open.

However, there is another loophole I see, and it involves the Deamidated gliadin antibody. This is a newer test, replacing the original gliadin antibody test.

The original gliadin antibody test was not considered specific to the finding of villous atrophy (required for a celiac disease diagnosis). The deamidiated gliadin antibody test was developed to be a better predictor of villous atrophy.

The loophole is that you can have gluten sensitivity without having celiac disease. This is something gaining recognition over the past years, but not quite to the point of complete, widespread acceptance.

So... on the one hand... in regard to predicting "celiac disease"... the deamidated gliadin test is a better test than the previous one. Step forward for diagnosing celiac disease (villous atrophy). This may help reduce the number of unnecessary biopsies.

BUT... big BUT... when it comes to diagnosing gluten sensitivity that is manifesting without villous atrophy... the newer deamidated gliadin test becomes as worthless as the anti-tissue transglutaminase test (also very specific for villous atrophy). Neither of these tests will be positive unless someone has villous atrophy. You can absolutely be gluten sensitive and symptomatic without having villous atrophy; without being positive on these blood tests. Step backward for diagnosing gluten sensitivity.

If your doctor is willing, try to get the original antigliadin antibody test ordered. You are more likely to test positive on the original gliadin antibody test than on the newer deamidated gliadin test.

Still, you should now, many people who test negative even on the original antigliadin test often improve on a gluten free diet. The blood tests are not perfect. When it comes to gluten sensitivity without celiac disease, the rate of "false negative" lab results increase. Hence, the popularity of the stool test for identifying crytpic gluten sensitivity.

It should be noted that even in cases of biopsy proven celiac disease, blood tests are negative in up to 20%. This is why if someone is highly symptomatic of celiac disease, they should be biopsied even when blood tests are negative.

I know I just dumped a lot here. Please ask for clarification if it doesn't all make sense.

Here are a couple of articles about IgA deficiency... keep in mind the distinction between IgA deficiency and Total IgA deficiency.

Celiac Disease and Immunoglobulin A Deficiency... by Kumar, et al.

Here are a couple others... the link was broken for the article I usually reference.. but this should help.
http://pediatrics.about.com/od/prima...deficiency.htm
http://www.nlm.nih.gov/medlineplus/e...cle/001476.htm

It might not be a bad idea to test for IgG subclass deficiencies as well.

And, here are some links to pages of The Gluten File that might help clarify some things on Gluten Sensitivity vs. Celiac Disease, Diagnostic Testing, etc. You can also scan the right bar for topics that may be of interest, particularly if there is any family history of other autoimmune disease.

Diagnostic Testing
The Gray Zone
Limitations of Blood / Biopsy
Gluten Sensitivity vs. Celiac Disease
At Risk Population for Gluten Sensitivity/Celiac Disease


Hope this helps!

Cara

I went gluten free primarily to support my daughter. My antibody tests were all negative. But, before long, a life time of nagging GI symptoms just vanished. I've also realized I am sensitive to cow's milk protein, too, as is my daughter. I say... if the shoe fits... wear it... I would absolutely recommend a gluten free diet if you are symptomatic in any way or have any family history of autoimmune disease!

My family's story can be found in The Gluten File at the bottom of the home page, if you are interested. My family is gluten sensitive, but we do not have celiac disease.

Selective IgA Deficiency -IDF Patient/ Family Handbook

Also on IgA deficiency affecting blood and stool testing:

I have heard some doctors say you don't need to worry about IgA deficiency in celiac testing unless you are completely deficient (less than 7)... that you still make enough IgA for it to show up on the tests.

I've heard other doctors, including one of the big specialists (but can't remember who) that below range IgA could affect those results. I would imagine it could go either way.

I think you are right that the stool testing is also based on IgA testing, and can be false negative in IgA deficient people. I'm pretty Dr. Fine addresses the subject somewhere on his website, but I couldn't find it just now. I would think if you are not completely IgA deficient, you'd have a higher chance showing positive on the stool test than the blood test... just because it is a much more sensitive test... but that a false negative would be possible. But, that is just my opinion.

Found it on the Enterolab website under FAQs:
https://www.enterolab.com/StaticPage...rpretation.htm

Quote:

What does it mean that my antigliadin antibody level is just below the upper limit of normal? . . . Although our stool test is multitudes more sensitive in picking up gluten sensitivity than blood tests, no single diagnostic test can rule out gluten sensitivity with 100% certainty (we estimate our antibody test misses about 1 in 500, about equal to the frequency of IgA deficiency in the general population). Thus, while it is very unlikely that a person with an antigliadin antibody level in the normal range has active gluten sensitivity, anyone with symptoms of gluten sensitivity and/or having an autoimmune disease, especially if accompanied by an antibody level just below the cut off, or with a gluten sensitive gene and/or intestinal malabsorption, should consider a 6-12 month trial of a gluten free diet, looking for improvement in symptoms, autoimmune disease severity, and/or intestinal malabsorption. It is only in this population that a gluten free diet should be considered a "trial"; all other people must consider gluten-free diet for positive tests definite and permanent therapy.

Isn't jccgf great?
 

One day, there might be citizen prizes awarded to those non-medical people who have most advanced the public's understanding of medical conditions and gotten medical people to consider their usual mode of behavior and even change it in light of accumulated evidence.

There are a number of people who come to mind, such as the Lorenzo's oil couple, but I'm nominating jccgf right up there, even if The Gluten File is not as easily made into a movie. :D

Thanks, Glenn. You give me too much credit, but I appreciate your kind words ;).

I noticed the links above were broken... and thought I should correct them in case the original poster returns to read them.

Diagnostic Testing

The Gray Zone

Limitations of Blood / Biopsy

Gluten Sensitivity vs. Celiac Disease

At Risk Population for Gluten Sensitivity/Celiac Disease

Thanks. VERY helpful. Thanks for the links to the IgA deficiency articles, too.

Can you tell me more about this? "It might not be a bad idea to test for IgG subclass deficiencies as well." Is that any relation to an ELISA test? I've heard of that.

Yes, I've thought about going GF w/ my daughter and I think we might if she only were gluten/casien free. But at this point she has so many digestive problems / sensitivities -- essentially on an SCD diet but even more limited than that -- that our whole family isn't yet prepared to join her in her diet. Getting some clear test results would help in that decision! Oh well.

You're welcome :).

IgG subclass testing breaks out total IgG, just like they test for total IgA.

IgG SUBCLASSES and TOTAL IgG
IgG 1
IgG 2
IgG 3
IgG 4
IgG, Serum

I am no expert in immunological testing. I do know the integrative doctor we saw did a lot of immunological testing on my daughter, including IgA and IgG subclass testing. She was below range in total IgA (they also broke out IgA1 and IgA2), and she was border low for IgG4. That did not seem to have significant meaning.

It is possible to be IgG deficient, too, so my guess is that like IgA deficiency can cause false results on antigliadin IgA tests, that an IgG deficiency could cause false results on antigliadin IgG tests.

You can have a normal total IgG level, but be deficient in one of the subclasses, which is why they break it out.

Quote:

"IgG subclass deficiencies may accompany IgA deficiency (see chapter titled Selective IgA Deficiency ). Combined deficiencies of IgA with IgG2 and IgG4 deficiency are frequently observed." IgG Subclass Deficiency and Specific Antibody Deficiency http://www.primaryimmune.org/publica...ats/e_ch10.pdf

As an aside, interesting in this Swine Flu season... is that deficiencies in IgG2 may be associated with more severe cases of swine flu: http://www.google.com/search?sourcei...ency+swine+flu

There is also IgG food allergy testing. This might be what you were wondering about. Traditional allergy testing looks only at IgE allergic responses... the type responsible for anaphylactic reactions. IgG food allergy testing is gaining popularity, particularly with "alternative" medicine docs. It is often termed delayed food allergy and may be associated with many chronic conditions. Many of the labs doing IgG food allergy testing are listed on the right bar toward the bottom of this page in TGF:

http://jccglutenfree.googlepages.com/foodallergy

When I talked w/ my dr about the selective IgA deficiency, she said she wondered if pregnancy [I'm 7 mon pregnant] could make my #s low. She's inclined to just wait ... maybe do another test a few months after the baby is born ... but then I'll be breast-feeding, and she doesn't know if that could affect my IgA levels....

Anyone have any knowledge about this? Thanks.

In July I had a scope of my stomach that ruled out celiac or as it is written in the report - neg. for sprue.

I just got back some new blood work and the Gliadin IGG AB was 68.2 ref. range <45. The only other thing out of range wasReticulocytes CGr 35.0 ref. range 25-30. The doctor suggested I try a gluten free diet. But as I understand this it does not indicate celiac. She said give the diet a try and see how I felt.

Is the IGG or the IGA a better marker for celiac?

Hi cat265,

I'm glad your doctor suggested you try a gluten free diet. Although your biopsy was negative, there are many many many cases of people who improve miraculously on a gluten free despite lack of a celiac diagnosis.

This comes down to the difference between gluten sensitivity and celiac disease. Celiac disease, by definition, requires villous atrophy. But, you can be gluten sensitive and have other related disease, such a dermatitis herpetiformis (skin manifestations) or gluten ataxia, or many other wide ranging symptoms, without showing villous atrophy. Gluten sensitivity that doesn't show as celiac disease (villous atrophy) has been a somewhat controversial subject for years, but science is finally beginning to back up what patients have known for decades... gluten causes problems for many who don't meet the diagnostic criteria of celiac disease. And, it may be relative in other autoimmune disease, as well.
http://jccglutenfree.googlepages.com...sceliacdisease
http://jccglutenfree.googlepages.com/zonulin

A positive antigliadin IgG does suggest you are gluten sensitive and will likely benefit from a gluten free diet. Left untreated, you may eventually progress to show villous atrophy. But, there are also those who will never show villous atrophy, but are symptomatic, and do respond to a gluten free diet.

The antigliadin IgA antibodies are more associated with a damaged gut, whereas antigliadin IgG may be more suggestive of non-gut manifestations..... but that is just a generality. My daughter had only a mildly positive antigliadin IgG, yet she had major gut symptoms, neurological symptoms and skin symptoms... and they all resolved on a gluten free diet.

I'm not sure what all of your symptoms are, but gluten sensitivity can cause wide ranging neurological symptoms (neuropathy, ataxia, white matter lesions, seizures, myopathy, and more), gastrointestinal symptoms, skin symptoms, can affect essentially any organ/tissue in the body, and is associated with several autoimmune diseases. If you have any symptoms at all, I'd definitely recommend a gluten free diet. About half of those with gluten sensitivity also have sensitivity to casein (cow's milk protein).


I'm not sure what this means~
Reticulocytes CGr 35.0 ref. range 25-30.
but here is the labtestsonline link for it:
http://www.labtestsonline.org/unders...te/glance.html

Thanks jccgf,

I have had not your typical symptoms; extreme muscle fatigue after exerction (eg. sometimes I can barely make it up a flight of stairs, if I do I have to sit for a few moments until the strength come back into my legs) though the weird thing about this is it comes and goes I could do the same activity the next day and not have the same reaction. Iam always tired. I did have an MRI that showed multipule lesions, I never got an answer as to what casued them. Brain fog/word recall has been a big issue. I did have a low b12 but Iam takeing care of that, my last blood test was 650 (or right around there) I guess my memory (right now I can't think of my symptom, its like I go to use my brain to think and its empty:confused:) and muscle fatigue are my worst symptoms

If your B12 serum level is now 650--
 

--which is not very high, by the way--one wonders what it was before you started "taking care of it" (which I assume means you are supplementing).

Gluten Sensitivity/celiac can certainly result in malabsorption of many nutrients (not just B-vitamins), and that may help to explain some of the fatigue, and it is possible to get central nervous system "plaquing" from B12 deficiency that superficially resembles that of CNS autoimmune diseases like MS.

Can you tell us, in more detail, what tests you're had, and what the results were?

Someone else mentioned cns/csf deficiency and I tried to google it but it was a little over my head. I didn't really understand it. About 2 years ago I was found to be b12 deficient, my level was 209. Because of blurred vison in spots, the dr. ordered an MRI. I came back showing multiple non-enhancing subcortical and deep white matter punctate hyperintensities in both hemisphers. I than had a lumbar puncture to rule out MS (no MS). I had an ANA test show positive 1:80 homogeneous pattern (ref range <1:40) Gliadin IGG AB slightly high at 68.2 (ref range <45) and Anti pareital cell pos. intrinsic factor neg. Alot of other antibody test where done, all were neg. Lyme come up 2 titers pos. so that test was considered negative as well.

I think my symptoms are probabley all from malabsorbtion issue as you mentioned. That makes the most sense.

cat... keep up with the B12 with a goal to get to the top quarter of range or over the top. The brain fog/ word recall problems may be related to the low B12. 9 years after initially correcting my B12 deficiency, I still struggle some with word recall, memory, and concentration problems... but this has greatly improved from its worst. However, these symptoms are also associated with gluten sensitivity.

Cognitive Impairment and Celiac Disease
http://archneur.ama-assn.org/cgi/con...ull/63/10/1440

Most everything that applies to "celiac disease" applies to gluten sensitivity. In gluten sensitivity that presents as celiac disease, the gut is the target organ, but gluten sensitivity can target the nerve, brain, and other organs without targeting the gut.

B12 deficiency and gluten sensitivity have many overlapping symptoms... and often occur together in the same person. You have symptoms and clinical evidence of both. (Low B12 level with parietal cell antibody, antigliadin IgG antibodies).

Gluten sensitivity is associated with neuromuscular problems, and they can be sporadic. There are a few articles in particular that come to mind by Dr. Marios Hadjivassiliou, the leader in gluten related neurological disease. Gluten ataxia itself can cause wide ranging symptoms, some of which fit what you describe.


Here is an accounting of Dr. Hadjivassilou's articles, with a couple excerpts that highlight the importance of a positive antigliadin IgG:
http://jccglutenfree.googlepages.com/halloffame

Of particular interest might be these articles:

You may have to register to get the full text of a couple of these, but if you send me your email addy via pm, I have most of them as pdf files that I could forward to you. The full text articles explain more in terms of patients individual symptoms than you find in the abstracts.

Neuromuscular disorder as a presenting feature of coeliac disease. Dec 1997
Free on Pubmed: http://www.ncbi.nlm.nih.gov/pmc/arti...v063p00770.pdf

Headache and CNS white matter abnormalities associated with gluten sensitivity. Feb 2001

Myopathy associated with gluten sensitivity, Dec 2006

Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Mar 2003
Free full text: http://brain.oxfordjournals.org/cgi/...full/126/3/685


Absolutely give a gluten free diet a trial. It must be a strictly gluten free diet, and it could take months to a year to see improvement...although my daughters neurological symptoms (including leg weakness, leg drag, limp body fatigue, drooping eyelids) all resolved within a couple of months. In the beginning she had fleeting episodes occuring months apart, eventually as often as several times a week, but they would last only for short periods of time... anywhere from 3-30 minutes. Near the end I could see very subtle symptoms always... in her gait... with bigger episodes coming and going.



Cara

Have they checked your potassium level when you are most symptomatic?

I do not know what it was when I was at my worst. I will try to look and see if I have a record of it. I do get muscle cramps fairly easily in my feet and calves when I to extend my foot, particualry in the morning.