|
Diagnosis
What are the appropriate
screening tests for celiac disease?
The tests of choice are
antibody measurements in the blood, ideally performed
before the patient has removed gluten from the diet.
However, patients and physicians must remember that no
screening test is perfect, and that the keys to
confirming the diagnosis of CELIAC DISEASE remain a
small intestinal biopsy combined with the patient’s
subsequent clinical response to a gluten-free diet.
Thus, a patient (especially a young child) with symptoms
of CELIAC DISEASE should have a small bowel biopsy, even
if the antibodies are not highly suggestive.
What are the different
antibody tests available? Can there be errors in
testing?
The blood tests can be
divided into 2 different types of antibodies: those
which are “anti-gluten”, and those that “anti-self”.
The “anti-gluten” antibodies are the anti-gliadin IgG
and IgA. Ig stands for “immunoglobulin” or
“antibody”. The “anti-self” antibodies are anti-endomysial
IgA and anti-tissue transglutaminase IgA (tTG). Each antibody test varies
widely in its sensitivity and specificity for predicting
whether the disease is present in any individual.
It must be remembered that NO test in medicine is
correct 100% of the time in each person!
There are
also several conditions which may yield false negative
antibody results. A false negative means that the
patient actually has the disease, but the test result is
negative. One of the conditions that may give a
false negative result is Immunoglobulin A or IgA
deficiency. If a patient has a low total IgA
level, the antibodies may be falsely low. For this
reason, it is recommended that a patient have a total IgA
level drawn at the same time the antibody testing is
done. Young children may not make the some of the
“anti-self” antibodies, as it takes a somewhat mature
immune system to make them. So in a young child,
antiendomysial antibody, or the TTG antibody, can have
false negative results. An inexperienced lab can
misread the anti-endomysial IgA test, which requires
someone to read a slide through a special microscope.
It is possible that a celiac patient could have a
positive antibody test at one lab, and a negative test
at another. This is because different labs may use
different commercial test kits, which vary in their
sensitivity and specificity. And lastly, a person
has to be ingesting gluten at the time the antibodies
are drawn. A gluten-free diet will make the
antibody tests negative.
Let’s
discuss the different antibodies and what the strengths
and weaknesses are for each.
Antigliadin antibodies
The antigliadin antibodies IgG and IgA recognize a small
piece of the gluten protein called gliadin. These
antibodies became available during the late 1970’s and
were the first step towards recognizing CELIAC DISEASE
as an autoimmune disorder. Antigliadin IgG has
good sensitivity, while antigliadin IgA has good
specificity, and therefore their combined use provided
the first reliable screening test for CELIAC DISEASE.
Unfortunately, many normal individuals without CELIAC
DISEASE will have an elevated antigliadin IgG, causing
much confusion among physicians. The antigliadin
IgG is useful in screening individuals who are IgA
deficient, as the other antibodies used for routine
screening are usually of the IgA class. It is thought
that 0.2-0.4% of the general population has selective
IgA deficiency, while 2 to 3% or more of celiacs are IgA
deficient.
If a
patient’s celiac panel is only positive for antigliadin
IgG, this is not highly suggestive for CELIAC DISEASE if
the patient has a normal total IgA level, corrected for
age. Younger children make less IgA than older
children and adults. A markedly elevated
antigliadin IgG, such as greater than three to four
times the upper limit of normal for that lab, is highly
suggestive of a condition where the gut is leakier to
gluten. This can happen in food allergies, cystic
fibrosis, parasitic infections, Crohn’s disease, and
other types of autoimmune GI diseases. These
antibodies may also be slightly elevated in individuals
with no obvious disease.
A strength of the antigliadin
antibodies is that they are ELISA tests. An
ELISA test also involves an antibody or antigen.
ELISA tests
are utilized to detect substances that have antigenic
properties, primarily proteins, such as gliadin.
The importance of an ELISA test is that it is rapid,
inexpensive, and run by a machine. Thus the
results are independent of observer variability.
The tTG test is also an ELISA test. This is in
contrast to the antiendomysial IgA, where a slide has to
be made, and a person has to look at it through a
microscope. These are more prone to human error.
Antiendomysium antibodies
The antiendomysial IgA antibody is an excellent screening
test for CELIAC DISEASE, with both a high sensitivity
and specificity. It is considered the gold
standard of antibodies. However, the subjective
nature of this test (someone still needs to look at the
slide under a microscope) may lead to false negative
values and unacceptable variability between
laboratories. This antibody was discovered in the
early 1980’s, and rapidly gained use as part of a
screening “celiac panel” by commercial labs in
combination with antigliadin IgG and IgA. Its
major drawbacks are that it may be falsely negative in
young children, in patients with IgA deficiency and a
lesser degree of villous atrophy, and in the hands of an
inexperienced laboratory.
Tissue transglutaminase
antibodies or TTG
Since tTG had been first
described as the autoantigen of celiac disease in 1997,
it has been utilized to develop innovative diagnostic
tools. The tTG IgA ELISA test is highly sensitive
and specific. The tTG assay correlates well with EMA-IgA
and biopsy. However, it represents an improvement
over the antiendomysial antibody assay because it
inexpensive, rapid, is not a subjective test, and can be
performed on a single drop of blood using a dot-blot
technique. One negative aspect of the TTG antibody
is that it can be falsely positive in a patient who has
another autoimmune condition. TTG false positivity
has been described in patients with both type I diabetes
and autoimmune hepatitis. Theoretically, it can
also be falsely positive in other autoimmune disease.
|
