<<Disclaimer: Verify this information before applying it to your situation.>>
The Listowners are in the process (which may take months) of making
revisions to the FAQ, and from time to time we will post additions which
we feel would be of immediate interest to the listmembers. The
following material on biopsies and blood tests is especially critical to
every celiac and his/her family. Therefore, even though it is long, we
are posting the information in full. We are splitting this post into
3 segments to make it easier to download on certain mail systems.
This file was prepared in cooperation with Vijay Kumar, M.D., Research
Associate Professor at the University of Buffalo and President and
Director of IMMCO Diagnostics, and Karoly Horvath, M.D., Ph.D.,
Associate Professor of Pediatrics; Director, Peds GI & Nutrition
Laboratory; University of Maryland at Baltimore. Both run laboratories
which provide services in the areas of autoimmunity, including tests for
celiac disease. Thanks to both!
Bill Elkus, for the CELIAC listowners
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Q. How long must gluten be taken for the serological tests to be
meaningful?
K (Dr. Kumar). There is no simple answer to this question as the
susceptibility of the patient to developing CD is dependent upon several
factors. One factor is the amount of gluten intake. Another is the
genetic makeup of the individual. However, we feel that several weeks
of gluten intake, especially in doses of 2 gm gluten/day, should result
in positive serology in patients with CD.
H (Dr. Horvath). The result of serological tests depends on the diet.
Generally, three to six months of a gluten-free diet may result in
normal antibody levels in a new patient. A strict gluten-free diet for
more than three months may result in inconclusive serological tests in
patients, who have started a diet without any diagnostic test. In this
case a gluten challenge should be introduced for a proper diagnosis.
Each patient has different sensitivity to gluten for reasons that are
unclear. The period of gluten challenge and the amount of gluten
necessary to provoke serological immune response are individually
different.
A 0.3 g/kg body weight/day of single gluten challenge causes
immunological changes (cellular immunity) in the intestine (J Pediatr
Gastroenterol Nutr 1989; 9:176-180) in patients on a gluten-free diet,
however, the serological response is much slower.
Our recommendation is to ingest at least 0.3 g/kg/day of gluten for two
months prior to the serological tests. However, if somebody experiences
symptoms during the gluten challenge we recommend to perform serological
tests earlier.
The protein content of wheat flour is between 7-15% and approximately
90% of the protein content is gluten. That means a slice of bread may
have 2-3 g of gluten.
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Q. What is the probability of false positive and false negative results
from the serological tests?
K. The three serological tests that are used for diagnosing CD are:
Anti-endomysial antibody (EMA)
Anti-reticulin antibody (ARA)
Anti-gliadin antibody (AGA)
Each of these three tests provide a certain degree of reliability for
diagnosing CD. Of these, endomysial antibody is the most specific
test. The following table is taken from our studies (Lerner, Kumar,
Iancu, Immunological diagnosis of childhood coeliac disease:
comparison between antigliadin, antireticulin and antiendomysial
antibodies). [Editor's note: view this in a monospaced font, such as
Courier, to get the numbers and titles to line up]
% Sensitivity % Specificity Predictive Value
% Pos. % Neg.
EMA 97 98 97 98
ARA 65 100 100 72
AGA
IgG 88 92 88 92
IgA 52 94 87 74
The following definitions related to sensitivity, specificity, positive
and negative predictive values may help.
Sensitivity is the probability of a positive test result in a patient
with disease.
Specificity is the probability of negative test result in a patient
without disease.
Positive predictive value is the probability of disease in a patient
with positive test result.
Negative predictive value is the probability of no disease in a patient
with negative test result.
H. The summary below shows the results of the main serological tests
based on several publications including 388 patients with CD, and 771
healthy subjects.
SENSITIVITY- the proportion of subjects with the disease who have a
positive test. It indicates how good a test is at identifying the
diseased.
IgA AGA: average: 78% range: 46-100%
IgG AGA: average: 79% range: 57-94%
IgA EMA: average: 97% range: 89-100%
SPECIFICITY- the proportion of subjects without the disease who have a
negative test. It indicates how good a test is at identifying the
nondiseased.
IgA AGA: average: 92% range: 84-100%
IgG AGA: average: 84% range: 52-98%
IgA EMA: average: 98.5% range: 97-100%
POSITIVE PREDICTIVE VALUE- the probability that a person with positive
results actually has the disease.
IgA AGA: average: 72% range: 45-100%
IgG AGA: average: 57% range: 42-76%
IgA EMA: average: 92% range: 91-94%
NEGATIVE PREDICTIVE VALUE- the probability that a person with negative
results does not have the disease.
IgA AGA: average: 94% range: 89-100%
IgG AGA: average: 94% range: 83-99%
IgA EMA: average: 100% range: 100%
REFERENCES:
McMillan SA, Haughton DJ, Biggart JD, Edgar JD, Porter KG, McNeill TA.
Predictive value for coeliac disease of antibodies to gliadin,
endomysium, and jejunum in patients attending for jejunal biopsy. Brit
Med J 1991;303:1163-1165
Ferreira M, Lloyd Davies S, Butler M, Scott D, Clark M, Kumar P.
Endomysial antibody: is it the best screening test for coeliac disease?
Gut 1992;33:1633-1637.
Khoshoo V, Bhan MK, Puri S, Jain R, Jayashree S, Bhatnagar S, Kumar R,
Stintzing G. Serum antigliadin antibody profile in childhood protracted
diarrhea due to coeliac disease and other causes in a developing
country. Scand J Gastroenterol 1989;24:1212-1216.
Chan KN, Phillips AD, Mirakian R, Walker-Smith JA. Endomysial antibody
screening in children. J Pediatr Gastroenterol Nutr 1994;18:316-320.
Bode S, Weile B, Krasilnikoff PA, Gdmand-Hyer E. The diagnostic value
of the gliadin antibody testing celiac disease in children: a
prospective study. J Pediatr Gastroenterol Nutr 1993;17:260-264.
Calabuig M, Torregosa R, Polo P, Tom s C, Alvarez V, Garcia-Vila A,
Brines J, Vilar P, Farr C, Varea V. Serological markers and celiac
disease: a new diagnostic approach ? J Pediatr Gastroenterol Nutr
1990;10:435-442.
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