Cereal Grain Proteins

Some Topics

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 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 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 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; Giera 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 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 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.

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