Frequently Asked Questions About Results Interpretation
Frequently Asked Questions About Results Interpretation
What is the numeric range of positive antigliadin antibody results?
Our antibody tests range numerically from a positive value of 10 to as high as 500
Units. The average positive value is about 45 Units. The "units" are based on the
amount of antibody detected in the assay which is reflected by more color developing
as the result of a color-generating chemical reaction. Thus, the more antibody present,
the higher the units of positivity. However, the amount of antibody present is not
a measure of clinical severity, but rather, the amount of antibody being produced
by the plasma cells in the intestine in response to gluten at that site. A positive
value of any degree means your immune system is reacting to dietary gluten in the
way the immune system reacts to an infection. With an infection, this immune reaction
ultimately kills and clears the infectious organism. But with gluten, the reaction
continues as long as it is eaten. Thus, the only way to halt this immune reaction
is to remove all gluten from the diet. This is true whether your positive test is
10 units, 500 units, or anything in between.
Are the numeric values of antigliadin antibody a measure of severity?
As mentioned above, the numeric value of antibody is not necessarily a measure of
severity of how your body is reacting to gluten, or the resultant damage of the
reaction. This is because the main perpetrator of the immune response to gluten
is not antibody but T lymphocytes (T cells) producing tissue-damaging chemicals
called cytokines and chemokines. How much antibody is produced at the stimulus of
T cells differs in different people. Furthermore, some people simply do not or cannot
make alot of intestinal IgA antibody even though gluten may be stimulating a severe
T cell-mediated immune response. Unlike antibody levels, the numeric value of malabsorption
test results are an indicator of severity of intestinal damage (see below).
If my antigliadin antibody levels are only mildly elevated, does that mean I can
eat some gluten?
This question is more "wishful thinking" resulting from the mind trying to turn
a positive test into what might want to be called "low positive" or even the equivalent
of negative. However from our experience, a positive antigliadin antibody of any
degree is like a positive pregnancy test. When a pregnancy test is positive, you
are not a little pregnant, you are pregnant. The same is true for gluten sensitivity.
Why is my antigliadin antibody elevated if I have been on a gluten-free diet?
There are several reasons why an antigliadin antibody test can be positive despite
being on a gluten free diet. The most obvious reason is that there may be hidden
gluten in the diet. Gluten is ubiquitous, and if a person does not prepare 100%
of their own food, one can not guarantee no gluten intake. Hidden gluten in unsuspected
sources or contaminating otherwise gluten-free foods is also possible. But more
often, the values are indeed on the lower end of positive, and previous values may
have been higher still. So in fact the "elevated value" in fact may represent a
marked improvement over previous antibody levels. Sometimes, however, people are
so immune suppressed from damage to the intestine and malnutrition that a gluten
free diet actually can make the antibody values go up for a time, a reflection of
enhanced immune function and response.
What does it mean that my antigliadin antibody level is just below the upper limit
All clinical laboratory tests must define a normal range that best distinguishes
those with disease from those without. Depending on what range is used to define
normal will determine how many people with disease will fall into the normal range,
and conversely, how many people without disease will fall into the abnormal range.
Our determined cut off for normal of 10 Units was derived after years of comparing
antibody levels with gene and malabsorptive test results, as well as clinical histories
before and after treatment with a gluten free diet. 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.
Is gluten-induced intestinal damage causing malabsorption reversible?
Gluten-induced intestinal damage is fully reversible provided gluten-free dietary
treatment is strict and permanent. However, the length of time to full healing and
disappearance of malabsorption depends on the severity and disease duration at onset
of treatment. Hence, children and those with more mild disease at onset of treatment
will resolve malabsorption quicker, usually within 6-12 months. Some adults with
severe disease, or those who do not quickly grasp or employ strictness to their
gluten-free diet, may have continued nutrient malabsorption for longer periods.
If intestinal malabsorption persists beyond 18-24 months, dietary and clinical re-evaluation
should be undertaken. Unlike antibody levels, our malabsorption test is a measure
of disease severity in the intestine. Values from 300 to 600 malabsorption units
represent mild malabsorption; 600-1000 moderate; 1000-1500 severe; and greater than
1500 very severe malabsorption (and possibly indicating a combination of gluten-induced
intestinal damage and insufficient pancreatic enzyme secretion).
Why do I need a gluten-free diet if I do not have intestinal damage?
So that you do not get it, or damage of any other organ. Prevention is the key to
lasting health. Once disease sets in, it is much harder and takes more healing energy
to reverse than it does to prevent it. An ounce of preventive health eradicates
a ton of disease. Do not wait for villous atrophy, osteoporosis, autoimmune disease,
or even symptoms to treat gluten sensitivity; prevent it all!
Do my positive results mean I have celiac sprue or that I need an intestinal biopsy?
The immune reaction to gluten is gluten sensitivity. Testing for the presence of
an antibody produced against gluten is the diagnostic hallmark of gluten sensitivity
(for years in the blood, and now more sensitively detected in stool with our testing).
Although the immune reaction to gluten, i.e., gluten sensitivity, is the cause of
the villous atrophy of celiac sprue, having these antibodies in stool, or even malabsorption,
does not necessarily mean you will have detectable villous atrophy in an intestinal
biopsy. But why does it matter, since it is known that a person can have every last
complication from gluten sensitivity and never have villous atrophy? In other words,
one can have gluten sensitivity damaging the intestine on a sub-microscopic level
destroying function, or damaging other organs/tissues without having celiac sprue.
Thus, there is no reason to expose yourself to the risks, invasive nature, and expense
of an intestinal biopsy. This idea is not new. Some have said this for years with
respect to positive antiendomysial antibodies. Now we extend this ideology to our
stool testing; if you have the immune reaction, and especially if you have detectable
malabsorption, symptoms, and/or immune disease, what is there to wait for to go
gluten-free? And if you have none of these consequences, why wait for them to appear?
Be thankful you do not, and go gluten-free.
Can autoimmune diseases or reactions improve with a gluten-free diet?
Clearly most immune-related damage in the intestine heals with a gluten-free diet.
Now it appears from early research of this question that many if not all autoimmune
diseases such as autoimmune thyroid disease, psoriasis, alopecia, arthritis, lupus,
hepatitis, diabetes, among others, and autism improve with a gluten-free diet. Because
the immune reactions to cow's milk proteins also are immune and autoimmune stimulating,
new research is focusing on the benefits of what has come to be called a gluten-free/casein-free
diet, which likely is more beneficial in this regard than a gluten-free diet alone
(see below). The less immune-stimulating the diet, the less fuel on which the immune
fire has to burn. Other immune-stimulating foods include other grains, legumes (including
soy), dietary yeast, and especially for arthritic patients, nightshades (tomatoes,
potatoes, egg plant, and hot red peppers).
Why are gene results so complicated, and which genes predispose to gluten sensitivity/celiac
Gene tests for gluten sensitivity, and other immune reactions are HLA (human leukocyte
antigen), specifically HLA-DQ, and even more specifically, HLA-DQB1. The nomenclature
for reporting HLA gene results has evolved over the last two decades as technology
has advanced. Even though the latest technology (and the one we employ at EnteroLab
for gene testing) involves sophisticated molecular analysis of the DNA itself, the
commonly used terminology for these genes in the celiac literature (lay and medical)
reflects past, less specific, blood cell-based (serologic) antigenic methodology.
Thus, we report this older "serologic" type (represented by the numbers 1-4, e.g.,
DQ1, DQ2, DQ3, or DQ4), in addition to the integeric subtypes of these oldest integeric
types (DQ5 or DQ6 as subtypes of DQ1; and DQ7, DQ8, and DQ9 as subtypes of DQ3).
The molecular nomenclature employs 4 or more integers accounting together for a
molecular allele indicated by the formula 0yxx, where y is 2 for DQ2, 3 for any
subtype of DQ3, 4 for DQ4, 5 for DQ5, or 6 for DQ6. The x's (which commonly are
indicated by 2 more numbers but can be subtyped further with more sophisticated
DNA employed methods) are other numbers indicating the more specific sub-subtypes
of DQ2, DQ3 (beyond 7, 8, and 9), DQ4, DQ5, and DQ6. It should be noted that although
the older serologic nomenclature is less specific in the sense of defining fewer
different types, in some ways it is the best expression of these genes because it
is the protein structure on the cells (as determined by the serologic typing) that
determines the gene's biologic action such that genes with the same serologic type
function biologically almost identically. Thus, HLA-DQ3 subtype 8 (one of the main
celiac genes) acts almost identically in the body as HLA-DQ3 subtype 7, 9, or other
DQ3 sub-subtypes. Having said all this, it should be reiterated that gluten sensitivity
underlies the development of celiac sprue. In this regard, it seems that in having
DQ2 or DQ3 subtype 8 (or simply DQ8) are the two main HLA-DQ genes that account
for the villous atrophy accompanying gluten sensitivity (in America, 90% of celiacs
have DQ2 [a more Northern European Caucasian gene], and 9% have DQ8 [a more southern
European/Mediterranean Caucasian gene], with only 1% or less usually having DQ1
or DQ3). However, it seems for gluten sensitivity to result in celiac sprue (i.e.,
result in villous atrophy of small intestine), it requires at least 2 other genes
also. Thus, not everyone with DQ2 or DQ8 get the villous atrophy of celiac disease.
However, my hypothesis is that everyone with these genes will present gluten to
the immune system for reaction, i.e., will be gluten sensitive. My and other published
research has shown that DQ1 and DQ3 also predispose to gluten sensitivity, and certain
gluten-related diseases (microscopic colitis for DQ1,3 in my research and gluten
ataxia for DQ1 by another researcher). And according to my more recent research,
when DQ1,1 or DQ3,3 are present together, the reactions are even stronger than having
one of these genes alone (like DQ2,2, DQ2,8, or DQ8,8 can portend a more severe
form of celiac disease).
Is it possible to tell which parent gave me the celiac or gluten sensitivity gene?
Everyone has two copies (or alleles as they are called scientifically) of every
gene in the body; one from mother and one from father. The only way to know if a
parent definitely has a gluten sensitive or celiac gene without testing them directly,
is if a child has two such genes (having received one from mother and one from father).
If only one gluten sensitive or celiac allele is present in a child, there is no
way to know if it came from mom or dad. One gene is enough, however, to get clinically
significant gluten sensitivity or celiac disease, and from published research, two
copies yields an even stronger reaction and hence, potentially more severe gluten-related
If I do not have a gluten sensitive or celiac gene, does that mean my parents/siblings/children
Because everyone has two copies (alleles) of every gene, but a parent only gives
one of these genes to each of their offspring (distributed randomly between a parent's
two alleles), even if a child does not have a gluten sensitive or celiac gene, one
or both parents could have one of these predisposing genes as their other allele.
Hence, a person without a predisposing gene could still have parents or siblings
with these genes. To be sure, each family individual must be tested to know. (The
only certainty with respect to genetic testing is that if a person is found to have
two predisposing genes, then every one of his/her children and both parents will
have at least one copy of these genes, which is enough to get clinically significant
gluten sensitivity or even celiac disease.) Because a child gets one allele from
each of their parents, even though a particular person does not have a gluten sensitive
gene, their children have a good chance of getting one from the other parent since
these genes are very common (see next paragraph).
How common are the gluten sensitivity and celiac genes?
DQ2 is present in 31% of the general American population. DQ8 (without DQ2) is present
in another 12%. Thus, the main celiac genes are present in 43% of Americans. Include
DQ1 (without DQ2 or DQ8), which is present in another 38%, yields the fact that
at least 81% of America is genetically predisposed to gluten sensitivity. (Of those
with at least one DQ1 allele, 46% have DQ1,7, 42% have DQ1,1, 11% have DQ1,4, and
1% have DQ1,9.) Of the remaining 19%, most have DQ7,7 (an allele almost identical
in structure to DQ2,2, the most celiac-predisposing of genetic combinations) which
in our laboratory experience is associated with strikingly high antigliadin antibody
titers in many such people. Thus, it is really only those with DQ4,4 that have never
been shown to have a genetic predisposition to gluten sensitivity, and this gene
combination is very rare in America (but not necessarily as rare in Sub-Saharan
Africa or Asia where the majority of the inhabitants are not only racially different
from Caucasians, but they rarely eat gluten-containing grains, and hence, gluten-induced
disease is rare). Thus, based on these data, almost all Americans, especially those
descending from Europe (including Mexico and other Latin states because of the Spanish
influence), the Middle East, the Near East (including India), and Russia, are genetically
predisposed to gluten sensitivity. (That is why we are here doing what we do!) But
be aware that if a person of any race has a gluten sensitive gene, and eats gluten,
they can become gluten sensitive.
Is milk protein sensitivity as bad as gluten sensitivity and do I need to be strict
with a dairy-free diet?
Research showing a high association of antibodies to cow's milk proteins in people
who react similarly to gluten has been around for over 40 years. More recent research
has now confirmed that these reactions to cow's milk proteins (mainly casein but
also lactalbumin, lactoglobulin, and bovine serum albumin) are indeed epidemiologically
related to autoimmune diseases such as diabetes, psoriasis, eczema, and asthma,
among others. While formal studies of dairy-free diets, either alone or in combination
with gluten-free, have not yet been conducted on a wide scale, the idea of a gluten-free/casein-free
diet is not new, having been employed for decades by many health practitioners.
From my objective assessment of this field, and my personal experience with my own
dietary elimination for health, I recommend complete avoidance of all dairy products
in anyone found to be immunologically sensitive to cow's milk protein by our tests,
and anyone with an established autoimmune or chronic immune disease. I predict future
research will support this recommendation. Do not bury your head in the sand waiting
for such studies. Do your own study and go gluten-free/dairy-free.
Is it okay to drink or eat goat or sheep's milk products if I am cow's milk protein
The main difference between the milk of cow's versus that of these smaller animals
is the percent protein content, being smaller in the smaller animals (because the
newborns do not have to grow as large as fast as calves grow to become cows; human
milk is even lower in protein relative to these animals). Thus, to consume products
made from goats or sheep is really to consume less of the protein. I believe this
is why these alternative milk products tend to be less antigenic than cow's milk
protein. Another potential reason is that goat's and sheep milk are consumed infrequently,
and hence established immune reactions are rare at the time they are introduced
to replace cow's milk. However, less antigenic is not "not antigenic." They are
still foreign proteins to the human body capable of, and often, stimulating immune
reactions in the intestine and body. It is like this from my perspective: mammals
(mammary animals) are supposed to suckle and drink their mother's milk until weaning,
when the conversion to their natural food source commences and ultimately replaces
the milk completely. The replacement is so complete that the genes breaking down
milk sugar lactose are down regulated to become absent because they are not to be
needed since milk is no longer to be consumed. This is what we call lactose intolerance
but is, in fact, the natural evolution of the gut mucosa. There really is no explanation
in natural terms that can justify an adult mammal consuming milk beyond the age
of weaning, much less the milk of another mammal. It is done (obviously), but it
is not natural (and seemingly not healthy).
What does it mean to be immunologically sensitive to the dietary yeast Saccharomyces
The immune system considers Saccharomyces cerevisiae foreign causing a reaction
that may damage the intestine and other tissues of the body, and/or possibly lead
to the development of or indicate the presence of Crohn's Disease.
What follow-up testing should I have and when?
The main abnormality of testing to be followed up with a repeat test is an abnormally
high malabsorption test. If this is not followed to normality, chronic malabsorption
may lead to nutrient, vitamin and mineral loss from the body, causing osteoporosis,
osteomalacia, calcium oxalate kidney stones, and other complications of chronic
malabsorption. The best interval for this follow up is one year. If moderate to
severe malabsorption persists despite a strict gluten-free diet, other causes, including
inflammatory bowel disease (especially Crohn's disease which is more common in gluten
sensitive people likely because of the associated immune reactivity to Saccharomyces
cerevisiae, dietary yeast) and deficient excretion of pancreatic enzymes,
should be considered. Follow up of an abnormal antigliadin antibody also can be
done at 1-2 year intervals as a guide to dietary compliance, but remember that in
the first year or two, the levels rarely go to normal, and sometimes, because of
enhanced immune function, may rise for a time before ultimately trending down. There
is no need to repeat a gluten sensitivity gene test.