by Stephen Gislason MD
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Some Topics from the
Dr Gislason's Preface
What is Gluten?
What is Celiac Disease?
Diseases Related to Celiac Disease
Digestive Tract Permeability
Gluten-Free Diet Revision
Gluten and the Brain
Gluten and Lung Disease
Gluten and Liver Disease
Gluten and Kidney Disease
Celiac Disease & Cancer
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 directing treatment.
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
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
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 noninvasive tests.
- Author Vogelsang H; Genser D; Wyatt J; Lochs H; Ferenci P; Granditsch G; Penner E
- 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 births).
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
- 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; Giera
- 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 bowel biopsy.
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
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
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.
Gluten Free: The exclusion of wheat, rye, barley are the initial steps
when gluten allergy is suspected. Gluten elimination should be part of a more comprehensive
diet revision plan, preferably in the form outlined in the Alpha Nutrition Program. The
Program is gluten-free and is recommended as the best diet revision strategy
for anyone with diagnosed celiac disease, or any person with symptoms suggestive
of gluten allergy. Learn more about the Alpha
Nutrition Program Gluten free recipes are found in the book,
Cooking and Recipes.
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