Diagnostic Testing
YOU MUST BE EATING GLUTEN FOR BLOOD AND BIOPSYTESTING TO BE ACCURATE!!!
RESULTS: Twenty patients could be followed during GFD and all antibody titres fell sharply within 1 month after introduction of a GFD and continued to decline during the survey interval. Thirty days after beginning the diet only 58, 84, 74 and 53% of all patients had positive antibody levels of tTGrh, tTGgp, EmA and AGA respectively.
Antibody levels in adult patients with coeliac disease during gluten-free diet: a rapid initial decrease of clinical importance. PMID: 15554953Are you scheduled for a biopsy? Are you eating gluten?
Any changes in your diet can affect the accuracy of your biopsy results. It is necessary for you to be eating gluten every day for at least 4-8 weeks before the procedure. If you are scheduled for a biopsy and are not eating gluten, talk to your doctor about what is necessary to obtain accurate results. If you have a biopsy and have eaten gluten only a short time before the test, you and your physician will not know if a negative test result is accurate or due to your diet.
University of Chicago Celiac Disease Center
If you are symptomatic and/or have tested positive to any of the antibody tests but failed to show biopsy damage, insist on periodic retesting. It is not uncommon for someone to have a negative biopsy one year, but a positive biopsy a couple of years later. It is also not uncommon to have negative blood tests for several years, which turn positive at a later date. And of course, even with a negative celiac biopsy, gluten sensitivity may be the cause of your symptoms. Read on!
A complete gluten sensitivity /celiac panel includes the following blood tests: anti-gliadin (AGA), IgA and IgG anti-deamidated gliadin (DGP), IgA and IgG anti-TG2 (TG2), IgA and IgG total serum IgA Being used in research: anti-TG6 (TG6), IgA and IgG (for neurological manifestion) anti-TG3 (TG3), IgA and IgG (for dermatitis herpetiformis) * * * IMPORTANT about Anti-gliadin antibodies! * * * A newer test, anti-deamidated gliadin, has been developed over the last several years and some labs are beginning to automatically substitute it instead of the original antigliadin antibody tests. The newer test is more specific to "celiac disease / villous atrophy", which is not helpful when looking for gluten sensitivity manifesting in non-gut ways (like neurological disease or other autoimmune disease), or when there are gut symptoms that have not yet caused villous atrophy. BE SURE your doctor orders the original antigliadin tests. DOUBLE CHECK that the right tests are ordered, and DOUBLE CHECK that the right tests were run. You want anti-gliadin IgA and anti-gliadin IgG, over anti-deamidated gliadin.... or all of them! Pubmed: Further explanation of the tests: To save cost, the celiac panel
is often reduced to a single test... the anti-tTG IgA. Insist on more
thorough testing than this single screening test! Total serum IgA should
always be run to rule out a condition called IgA deficiency. The other IgA
tests are not reliable measures in someone who does not make enough
IgA. The anti-endomysial antibody test is very specific for villous atrophy, but it has been replaced by the newer anti-tTG test. In a perfect world, anti-tTG and anti-endomysial will be in alignment, but in the real world sometimes one is positive and other not. A thorough doctor will run both. Reticulin antibodies have fallen out of favor even longer ago, but I do know of one person diagnosed with biopsy proven celiac disease who had only an isolated positive anti-reticulin antibody.
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UNIVERSITY OF MARYLAND CENTER FOR CELIAC RESEARCH RECOMMENDATIONS
The University of Maryland Center for Celiac Research still includes the antigliadin IgA and IgG tests in their celiac panel. Dr. Fasano, who heads this center, is world reknown for his work with celiac disease.
What are the recommended blood tests to diagnose CD?
There is a particular series of blood tests called the ‘Celiac Panel”. These tests measure your immune system’s response to gluten in the food you eat.
tTG-IgA or tissue transglutaminase-IgA
AGA-IgG or Antigliadin IgG
AGA-IgA or Antigliadin IGA
Total IGAThe presence of tTG antibodies is highly suggestive of CD, while AGA can be elevated also in cases of wheat allergy.
Based upon this 2010 article by Drs. Fasano and Catassi, they propose a 4 out of 5 rule for diagnosing celiac disease:
Celiac disease diagnosis: simple rules are better than complicated algorithms.
PMID: 20670718 Aug 2010Proposed by Drs. Fasano and Catassi:
The diagnosis of celiac disease is confirmed if at least 4 of the following 5 criteria are satisfied:
1) typical symptoms of celiac disease;
2) positivity of serum celiac disease immunoglobulin A class autoantibodies at high titer;3) human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes;
4) celiac enteropathy at the small bowel biopsy;
5) positive response to the gluten-free diet.
And... does antigliadin antibody testing have a place after all?
Testing for gluten-related disorders in clinical practice: The role of serology in managing the spectrum of gluten sensitivity.
PMID:21523259 April 2011
This article contains a great diagnostic
flowchart (figure 5) and provides a wonderful overview
Gluten-Sensitive
Enteropathy (Celiac Disease): More Common Than You Think by David A.
Nelson, JR, MD, MS
What do the antibody tests mean?
Having a
positive anti-tTG or anti-endomysial result means there is a very high
probability (90-95%) that villous atrophy will be found on biopsy.
However, a negative anti-tTG result does not absolutely rule out celiac
disease~ it just makes it less likely.
Because a positive
anti-tTG is such a strong indicator of intestinal damage, the trend
seems to be moving away from using the gliadin antibody testing at all.
Isolated gliadin antibodies are a weaker indicator that the intestinal damage needed for a Celiac Disease diagnosis will be found. However, gliadin antibodies can be very meaningful, particularly for those who present with neurologic disease. There are also many people who have gastrointestinal and other symptoms that improve on a gluten free diet, whose only hint of a problem with gluten were positive antigliadin antibodies.
Insist they include the antigliadin IgA / IgG, especially if you have neurologic or other non-intestinal symptoms.
M Hadjivassiliou, R A Grünewald, G A B Davies-Jones
”But antigliadin antibodies lack
specificity”
IgG anti-gliadin antibodies have been
the best diagnostic marker in the neurological
population we have studied. IgG
anti-gliadin antibodies have a very high
sensitivity for CD but they are said to
lack specificity. In the context of a range
of mucosal abnormalities and the concept
of potential CD, they may be the
only available immunological marker for
the whole range of gluten sensitivity of
which CD is only a part. Further support
for our contention comes from our HLA
studies. Within the group of patients
with neurological disease and gluten
sensitivity (defined by the presence of
anti-gliadin antibodies) we have found a
similar HLA association to that seen in
patients with CD: 70% of patients have
the HLA DQ2 (30% in the general population),
9% have the HLA DQ8, and the
remainder have HLA DQ1. The finding of
an additional HLA marker (DQ1) seen in
the remaining 20% of our patients may
represent an important difference between
the genetic susceptibility of patients
with neurological presentation to
those with gastrointestinal presentation
within the range of gluten sensitivity.
”But antigliadin antibodies have
been superseded by
anti-endomysial and
transglutaminase antibodies”
The introduction of more CD specific
serological markers such as antiendomysium
and more recently transglutaminase
antibodies may have helped
in diagnosing CD but their sensitivity as
markers of other manifestations of gluten
sensitivity (where the bowel is not
affected) is low. This certainly reflects
our experience with patients with gluten
sensitivity who present with neurological
dysfunction. Endomysium and transglutaminase
antibodies are only positive
in the majority but not in all patients
who have an enteropathy. Patients with
an enteropathy represent only a third of
patients with neurological manifestations
and gluten sensitivity. Antigliadin
antibodies unlike endomysium and
transglutaminase antibodies are not autoantibodies.
They are antibodies against
the protein responsible for gluten sensitivity.
SERONEGATIVE CELIAC DISEASE EXISTS
It is also possible to
have seronegative celiac disease. Some studies say this may occur in as
many as 20%. A negative result on all antibody tests does not completely
rule out celiac disease. If someone is highly symptomatic they should
pursue a biopsy even if all blood work is negative.
Seronegative celiac disease: increased prevalence with
lesser degrees of villous atrophy.
PMID: 15185855
Reliance on serum endomysial antibody testing
underestimates the true prevalence of coeliac disease by one fifth.
PMID: 10720117
Anti-endomysial antibody negative celiac
disease: does additional serological testing help?
PMID:
11270789
DO I NEED A BIOPSY?
For a "gold standard" diagnosis,
yes..you need a biopsy. If a "gold standard" diagnosis is not important
to you, nobody can force you to have a biopsy if you don't want one.
Some people are happy to let their response to the diet speak for
itself. Others want to have a solid diagnosis before committing to
strict dietary changes for a lifetime. Most, but not all, doctors will
recommend a biopsy to confirm the diagnosis.
One thing is for sure, if you think you will ever want
to have a biopsy done...the time to do it is BEFORE you begin
experimenting with a gluten free diet. You must be consuming gluten for
the biopsy to be accurate.
A biopsy may be important
to rule out other co-existing conditions which might be contributing to
your symptoms. However, if symptoms do not improve with dietary changes,
a biopsy could always be performed at a later date.
Some doctors
who take a common sense approach will diagnosis celiac disease based
upon positive blood work and/or symptoms which improve on a gluten free
diet alone. A positive anti-tTG, for example, is a very strong indicator
that damage will be found on biopsy. So strong, in fact, that some
doctors are beginning to question the necessity of performing the
invasive procedure.
Is
intestinal biopsy always needed for diagnosis of celiac disease?
PMID: 12818277
Whether
or not you need biopsy proof of celiac disease is a personal decision
to be made by you and your doctor. There are many pro's and con's to be
considered, and a case can be built in either direction.
Clearing you of Celiac Disease today does NOT clear you for life.
Celiac disease in first-degree relatives of patients.
PMID: 20711550 July 2010
We conclude that one-time testing for celiac disease among families with affected members is insufficient. Repeat testing should occur irrespective of the presence of symptoms.
Screening for Celiac Disease in Family Members: Is Follow-up Testing Necessary?
PMID: 17380406 April 2007
Among 11 relatives, at the time of the first screening, 6 already had a positive serology and histology for CD, while 5 became positive only after a period of 2 to 5 y of negative testing. Conclusion: CD can manifest itself after years of negative serological testing.
Onset of coeliac disease: a prospective longitudinal study.
PMID: 14632329 Oct 2003
Also: Follow-Up to the Catassi Study -- Scandinavia
Colin, et al, published a follow-up study to the Catassi (Coeliac Disease in the Year 2000:Exploring the Iceberg - University of Ancona, Italy) in the Scandinavian Journal of Gastroenterology 28(7):595-8, 1993, which demonstrated that approximately one third of the patients from the Catassi Study who had raised antibodies but no villous atrophy, did have villous atrophy when tested two years later. These results raise the number of diagnosed celiacs from the Catassi, et al study to over 1 in 200.