Antibody Tests Non-Invasive and Screening
Physicians are preoccupied with tests, believing that test results are more
scientific than real life information. Patients want simple answers to complex
problems. The reality that I confronted for many years was that very sick
patients would get better with diet revision that excluded gluten regardless of
their laboratory test results. My attitude is that positive antibody tests
are interesting findings in research, but may not be helpful in the management
of sick patients. I concluded that negative test results were not helpful in
A prevalent attitude of physicians is that proper diet revision is too
difficult to undertake and they would not consider diet revision to be a
suitable experiment to undertake when a patient was chronically ill and not
benefiting from treatments offered. I believe that the primary duty of the
physician is to find an effective treatment for disease.
Tests, such as anti-gliadin, anti-endomysium, and anti-transglutaminase
antibody estimation can be used as screening tests in groups considered at risk
of celiac disease. These include first-degree relatives of celiac patients and
patients with irritable bowel syndrome, arthritis, diabetes mellitus,
iron-deficiency anemia, epilepsy, cerebellar ataxia, autoimmune diseases,
depression, weight loss and malnutrition. While these antibody tests are useful
in identifying potential celiacs, they should not be used to “rule out’ celiac
disease nor can they exclude a wider range of gluten-induced diseases.
Since intestinal biopsy, by definition, is required for a diagnosis of celiac
disease (CD), researchers have looked for and found non-invasive tests that
correlate well with biopsy results. The first antibody test to emerge was the
detection of serum anti-gliadin antibodies. The logic follows traditional
allergy practice, where the finding of antibody against a food antigen, suggests
that the antigen has a pathogenic role.
Transglutaminase antibodies (TGA) are the most recent
markers of CD. Transglutaminase is a normal enzyme and it appears to be the main
antigen target for AEA. In a study of 181 celiac patients Scoglio
et al reported high
correlations of antibody results with intestinal biopsy and suggested that
antibody tests repeated in patients with high probability of having the disease
could replace biopsy.
Gliadin is just one protein among many in the gluten complex. Digestion of
gliadin produces a number of peptides that are likely to be the active agents of
disease. Remember that are 4 majors classes of antibodies and many subtypes. It
is estimated that one person can make a large number of antibodies that interact
with a million or more targets.
Every person has circulating serum antibodies to some food proteins, but
there is no easy cause and effect connection between the presence of antibody
and the activity of a disease. While some diseases are marked by the presence of
a specific antibody, no disease can be reliably diagnosed by the presence or
absence of single antibodies. An antibody that is made to interact with one
target may also interact incidentally with other targets. The original target
may be a food protein and the incidental target maybe cells in normal tissues
that are damaged by an immune attack.
Screening for celiac disease: a prospective study on the value of
- Author Vogelsang H; Genser D; Wyatt J; Lochs H; Ferenci P; Granditsch G;
- Source Am J Gastroenterol, 1995 Mar, 90:3, 394-8
- Abstract OBJECTIVE: Celiac disease is frequently diagnosed in patients
with nonspecific abdominal symptoms. Therefore, highly sensitive,
specific, and simple noninvasive screening tests are needed. METHODS: This
study compared the usefulness of IgG- and IgA-antigliadin antibodies,
IgA-endomysial antibodies, and intestinal permeability in diagnosing
celiac disease in 102 adult patients with nonspecific abdominal symptoms.
In addition, all patients underwent small bowel biopsy as a gold standard
for the diagnosis of celiac disease. RESULTS: Forty-nine patients were
ultimately diagnosed as having celiac disease because of flat mucosa.
Flatulence and signs and symptoms dating back to childhood were more
frequent and abdominal pain less frequent (p < 0.05) in celiac disease but
were not helpful for screening. IgA-endomysial antibodies showed a
sensitivity and specificity of 100%; an altered intestinal permeability
had also a 100% sensitivity, but only 55% specificity. IgG- and
IgA-antigliadin antibodies' sensitivity (73% and 82%, respectively) and
specificity (74% and 83%, respectively) were much lower. Combining the two
antigliadin antibodies did not significantly improve the sensitivity and
specificity. CONCLUSIONS: Our data show the advantage of IgA-endomysial
antibodies for screening of celiac disease except in the case of patients
with IgA-deficiency or dermatitis herpetiformis. In these patients, the
permeability test could improve noninvasive differential diagnosis.
IgA antigliadin antibodies as a screening method for nonovert celiac disease
in children with insulin-dependent diabetes mellitus.
- Author Calero P; Ribes-Koninckx C; Albiach V; Carles C; Ferrer J
- Source J Pediatr Gastroenterol Nutr, 1996 Jul, 23:1, 29-33
- Abstract One hundred forty-one children with insulin-dependent
diabetes mellitus were screened for serum immunoglobulin A (IgA)
antigliadin antibodies by means of an enzyme-linked immunosorbent assay
(ELISA) method. None of them had gastrointestinal symptoms, and no major
nutritional disturbances were detected except for a girl with moderate
growth delay. Twelve patients with positive IgA antigliadin antibodies on
two or more consecutive measurements underwent a small intestinal biopsy;
four of them had a subtotal villous atrophy, and celiac disease was
diagnosed; in another patient, a partial villous atrophy was observed.
Children suffering from both diabetes and celiac disease showed an onset
of diabetes at a younger age than did nonceliac patients. Prevalence of
celiac disease in the screened population is 2.85%, which is higher than
in the general population of the Comunidad Valenciana (one in 2,500 live
Preliminary results from follow-up of a large-scale population survey of
antibodies to gliadin, reticulin and endomysium.
- Author Johnston SD; Watson RG; McMillan SA; McMaster D; Evans A
- Source Acta Paediatr Suppl, 1996 May, 412:, 61-4
- Abstract Coeliac disease is often under-diagnosed, particularly in
cases which are atypical or asymptomatic. OBJECTIVE: The aim of this study
was to comprehensively assess the prevalence and clinical profile of adult
coeliac disease in our community. METHODS: One-hundred-and-thirteen
subjects from the most recent MONICA (multinational MONItoring of trends
and determinants in Cardiovascular disease)1991/2 survey with positive
serology were followed up 3 years after initial screening and assessed by
means of (i) a clinical questionnaire, (ii) screening blood tests, and
(iii) jejunal biopsy. RESULTS: Forty-six subjects (21 male, mean age 51
years) have been followed up to date. Prior to follow-up, two of these
subjects were diagnosed as having coeliac disease. Ten (3 male, mean age
51 years) of 44 subjects had enteropathy. Three of these 10 subjects were
relatively asymptomatic, 3 had folate deficiency and 3 had iron
deficiency. Thus 12 of the 1823 initially screened had enteropathy
consistent with coeliac disease. CONCLUSIONS: Coeliac disease is more
prevalent than previous estimations and was found to be at least 1 in 152.
Diagnostic value of various serum antibodies detected by diverse methods in
childhood celiac disease.
- Author Sacchetti L; Ferrajolo A; Salerno G; Esposito P; Lofrano MM; Oriani
G; Micillo M; Paparo F; Troncone R; Auricchio S; Salvatore; F
- Source Clin Chem, 1996 Nov, 42:11, 1838-42
- Abstract The diagnostic performances of antiendomysium IgA detected on
monkey esophagus and human umbilical cord smooth muscle, of antireticulin
IgA, and of antigliadin IgA and IgG were calculated in 74 children with
celiac disease (CD) or other gastrointestinal disorders. We also compared
four methods for gliadin antibody detection. With a diagnostic specificity
of 100%, diagnostic sensitivity was 94% for antireticulin IgA, 93% for
antiendomysium IgA when detected on human umbilical cord smooth muscle,
and 97% when detected on monkey esophagus. The diagnostic sensitivity for
gliadin antibody was highest with an ELISA procedure, followed by
fluorogenic detection (94% for IgG, 91% for IgA, 97% with IgA and IgG
combined). Because of its high diagnostic sensitivity and ease and speed
of use, the combined antigliadin IgG and IgA antibody assay is suitable
for screening large groups of patients. In IgG- or IgA-positive cases, the
more demanding and more specific antiendomysium IgA evaluation is required
to confirm suspected CD.
Serum and salivary antigliadin antibodies and serum IgA anti-endomysium
antibodies as a screening test for coeliac disease.
- Author Rujner J; Socha J; Barra E; Gregorek H; Madali?ski K; Wo?niewicz B;
- Source Acta Paediatr, 1996 Jul, 85:7, 814-7
- Abstract Serum and salivary IgA and IgG antigliadin antibodies were
determined by an enzyme-linked immunosorbent assay in 18 children with
villous atrophy and 30 children on a gluten-free diet for coeliac disease
in whom normal intestinal mucosa was found. Serum IgA anti-endomysium
antibodies were also determined by an immunofluorescence method in these
children. Serum IgG antigliadin and IgA anti-endomysium antibodies had the
highest sensitivity (100 and 94.4%, respectively), followed by serum IgA
antibodies to gliadin (72.2%), salivary IgA antigliadin (61.2%) and IgG
antigliadin (50%) antibodies. The highest specificity was found for serum
IgA anti-endomysium (100%) and IgA antigliadin (96.6%) antibodies and
salivary IgA and IgG antigliadin antibodies (93.3%), while serum IgG
antigliadin antibodies were found to be least specific (63.3%).
Is small bowel biopsy necessary in adults with suspected celiac disease and
IgA anti-endomysium antibodies? 100% positive predictive value for celiac
disease in adults.
- Author Valdimarsson T; Franzen L; Grodzinsky E; Skogh T; Str?m M
- Source Dig Dis Sci, 1996 Jan, 41:1, 83-7
- Abstract The comparative diagnostic value of IgA anti-endomysium and
IgA antigliadin antibodies in adults with histologically confirmed celiac
disease is reported. Sera from 144 adult patients (without concurrent
dermatitis herpetiformis or IgA deficiency) who underwent small bowel
biopsy were analyzed for both IgA anti-endomysium and IgA anti-gliadin
antibodies. Nineteen patients (13%) had celiac disease. The presence of
IgA antiendomysium antibodies had a sensitivity of 74% and a specificity
of 100%. The positive and negative predictive values were 100% and 96%,
respectively, and the diagnostic accuracy was 97%. In contrast, IgA
anti-gliadin antibodies had positive and negative predictive values of 28%
and 96%, respectively, with a diagnostic accuracy of 71%. Based on these
data, we suggest that small bowel biopsy is not necessary to diagnose
celiac disease in symptomatic adults with IgA antiendomysium antibodies.
Due to a negative predictive value of 96%, some symptomatic adults lacking
anti-endomysium antibodies will not be correctly diagnosed without small
IgA and IgG binding components of wheat, rye, barley and oats recognized by
immunoblotting analysis with sera from adult atopic dermatitis patients.
- Author Varjonen E; Kalimo K; Savolainen J; Vainio E
- Source Int Arch Allergy Immunol, 1996 Sep, 111:1, 55-63
- Abstract IgA and IgG antibody response of adult atopic dermatitis patients
against neutral/ acidic fractions of wheat, rye, barley and oats was analyzed
utilizing an immunoblotting method. Moreover, the antibody response against
ethanol-soluble fraction of wheat was examined with serum pools of healthy
donors, atopic dermatitis patients and patients with dermatitis herpetiformis or
adult celiac disease. All patient sera revealed polymorphic IgA and IgG binding
to cereal peptides with molecular weights of 11-97 kD. The antibody staining was
essentially identical with atopic dermatitis patients and controls. Patients
with dermatitis herpetiformis or celiac disease showed more intensive staining
with the ethanol extract of wheat and showed more IgA-stained bands in
immunoblotting. It seems that the presence of IgA and IgG antibodies to
different cereal antigens is a result of natural exposure and in atopic
dermatitis displays little diagnostic significance, in contrast to antigliadin
antibody response in dermatitis herpetiformis and celiac disease.
Measurement of sugar probes in serum: an alternative to urine measurement in
intestinal permeability testing.
- Author Fleming SC; Duncan A; Russell RI; Laker MF
- Source Clin Chem, 1996 Mar, 42:3, 445-8
- Abstract The percentage dose of lactulose and mannitol excreted in
urine after oral ingestion is used as a noninvasive method of assessing
small intestinal permeability. The collection of incomplete or
inaccurately timed urine samples can lead to errors in estimation of sugar
probe molecules. We describe an HPLC method for the simultaneous
determination of lactulose and mannitol in serum after oral ingestion of
test sugars. We applied the test to healthy volunteers and to subjects
undergoing jejunal biopsy for suspected gluten-sensitive enteropathy. The
ratio of concentrations of lactulose and mannitol in serum discriminated
well between subjects with a normal biopsy and those with villous atrophy,
discrimination being best at 90 min postdose. The results agree well with
lactulose:mannitol ratios determined in urine (r= 0.88), and the two
methods can be used interchangeably. The determination of mannitol and
lactulose in serum provides an acceptable alternative to urine collection
and may be particularly useful in young children. It also reduces the time
spent on the investigation from 5 h to 90 min.
- The book, Gluten Problems and Solutions provides both an
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