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Objective: The aim of this study was to investigate the metabolic function of intestinal microflora in children with screening-detected celiac disease (CD) to see if there is an aberrant gut flora in screening-detected CD similar to symptomatic CD and contrary to healthy controls., Materials and Methods: As part of a Swedish multicenter screening for CD, 912 12-year-old children were screened with serum anti-human tissue transglutaminase-IgA. Small bowel biopsy specimens from children with positive serology revealed 17 individuals with CD. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. Our previously published findings in children with symptomatic CD and healthy controls were used as comparison., Results: The children with screening-detected CD had a similar fecal SCFA profile to children with symptomatic CD, but differed significantly from that in healthy children., Conclusions: This is the first study on SCFA patterns in fecal samples from children with screening-detected CD. The similarity of the fecal SCFA profile in screening-detected and symptomatic CD indicates common pathogenic mechanisms. This could open the way for new therapeutic or prophylactic measures based on novel biological principles.

Aim: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD)., Methods: Children with suspected CD and positive EMA (>or=1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n=133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n=39; 59% female, mean age at the first biopsy 7.3 years, range 1.4-16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n=94; 56% female; mean age 7.6 years at the first biopsy, range 0.70-17)., Results: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2-7 years (median 4.5 years)., Conclusions: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.

Background: The use of oats in a gluten-free diet for children with coeliac disease is presently under investigation. In this study we measured the content of antibodies to oat prolamines (avenin) in sera from coeliac children and reference children., Methods: Crude avenin was prepared by extraction with ethanol and salt-solution and used as antigen in a three-step ELISA. Sera from 81 children, including 34 children with verified coeliac disease, were analysed for both IgA and IgG antibodies to avenin and gliadin. Sera were also incubated with gliadin before exposure to avenin, and vice versa, to assess a possible cross-reaction between the species. Keyhole limpet hemocyanin (KLH) was used as a negative control., Results: Children with coeliac disease on a normal diet had significantly higher levels of antibodies to avenin, both IgG and IgA, than reference children (P < 0.001) and the levels correlated positively with gliadin antibodies, especially of IgA-type (r = 0.798). Both anti-avenin and anti-gliadin antibodies were only absorbed by the corresponding protein., Conclusions: Children with coeliac disease have antibodies to oat proteins at significantly higher levels than reference children. The absorption test did not indicate a cross-reactivity between the prolamines of wheat and oats. The method will be employed for repeated sampling of anti-avenin antibodies during a prospective interventional study with a gluten-free diet supplemented with oats.

Background: Previously, a gluten challenge was customary to establish the diagnosis of celiac disease in children. There are no clear recommendations on how to perform this challenge or what markers to rely on for timing the biopsy after the challenge. The authors' aim was to monitor gluten intake, clinical symptoms, and antibody kinetics to evaluate the influence of gluten exposure during the challenge., Methods: Twenty-five children under investigation for suspected celiac disease were challenged. One child was excluded because blood samples, food records, or biopsy was lacking. Median age at the postchallenge biopsy was 3.8 (2.7-8.8) years. The families kept daily records of the children's gluten intake and of symptoms that occurred. Blood samples were taken monthly for analysis of antigliadin and endomysium antibodies and total immunoglobulin A (IgA). A third biopsy was performed when clinical symptoms suggested a relapse., Results: All 24 children showed deterioration of the mucosa or elevated antibodies during gluten challenge. Median duration of the challenge was 13 (5-51) weeks, and mean gluten intake was 1.7 (0.2-4.3) g/d and 0.1 (0.02-0.26) g/kg daily., Conclusions: Gluten intake during the challenge varied widely, and the parents were unable to give their children the recommended amount. Despite the small amounts given, all children showed signs of relapse at a clinical, laboratory, or histologic level. Much smaller amounts of gluten than previously suggested seem sufficient to cause relapse during gluten challenge in children.

Anti-gliadin and anti-endomysium antibodies were analyzed in 174 children with suspected or verified coeliac disease with the aim of developing a practical routine. The biopsy was performed without knowledge of the antibody levels. To screen for coeliac disease is children younger than 2 years, we suggest the use of IgA anti-gliadin antibodies, giving a sensitivity of 100% and a specificity of 86%. In older children both tests should be used in parallel, i.e. a biopsy should be performed if at least one of the tests is positive, giving a sensitivity of 98% and a specificity of 81%. To avoid unnecessary biopsy before mucosal relapse can be demonstrated during gluten challenge in a child without clinical symptoms, we suggest that the tests are used as serial testing, i.e. a biopsy should be performed if both tests are positive.

To assess whether dietary antigens play a role in inflammatory bowel disease, 26 monozygotic twin pairs with inflammatory bowel disease and 52 healthy controls were investigated for serum antibodies (IgA, IgG, IgM) against ovalbumin, betalactoglobulin, gliadin, whole yeast (Saccharomyces cerevisiae) and yeast cell wall mannan. The twins were made up of five pairs concordant and nine pairs discordant for Crohn's disease, and two pairs concordant and 10 pairs discordant for ulcerative colitis. Two patients with Crohn's disease had a slight increase in disease activity, the others were in clinical remission. Two striking observations were made: first, individuals with ulcerative colitis were indistinguishable from healthy twins, and controls except for the response to gliadin. Both healthy and diseased twins had higher IgA levels to gliadin than controls. Second, twins who had developed Crohn's disease displayed higher antibody titres towards yeast cell wall mannan in particular, but also to whole yeast (Saccharomyces cerevisiae) of all antibody types (IgA, IgG, and IgM). In contrast, the response to gliadin, ovalbumin, and betalactoglobulin did not differ from healthy twins and was even lower than in the controls. The results argue against an increased systemic antigen presentation caused by an impaired mucosal barrier in the inflammatory bowel disease. Rather, they suggest that yeast cell wall material--that is, mannan, or some antigen rich in mannose and cross reacting with mannan, may play an aetiological role in Crohn's disease, but not in ulcerative colitis. The increases in IgA and IgM, as well as IgG suggest that local and systemic immune systems are selectively activated by antigen(s) present in the cell wall of baker's yeast.

Rough Salmonella typhimurium 395 MR 10 bacteria sensitized with SIgA were used to assess the effect of secretory IgA (SIgA) on bacterial association with the intestine of rat and with a column of hog gastric mucin, and on IgG-mediated surface properties and interaction with polymorphonuclear leucocytes. It was found that SIgA increased the affinity for mucus belt of the intestine and for the mucin column, but reduced IgG-enhanced phagocytosis and surface hydrophobicity and charge of the bacteria. It is suggested that the ability of SIgA to render bacteria mucophilic and to modify IgG-mediated reactions serve the purpose of secluding bacteria from contact with mucosal membranes and depress inflammatory reactions at the site of infection.

A hydrophilic effect of human colostrum and colostral antibody SIgA binding on Escherichia coli o86 has been demonstrated by hydrophobic interaction chromatography on Octyl-Sepharose and partition in a polymer two-phase system containing dextran, poly(ethyleneglycol) and poly(ethyleneglycol)-palmitate. Furthermore, antibody SIgA binding reduced the negative surface charge of the E. coli bacteria. The reaction between centrifuged but not further purified colostrum and bacteria yielded a complex which, compared to bacteria alone, showed decreased negative and increased positive surface charges, the latter being sensitive to pepsin. Binding of SIgA or colostrum to E. coli showed no definite effect on the attachment to and phagocytosis by polymorphonuclear cells in vitro. The effects observed are discussed in relation to the structure of SIgA.

Serum levels of IgG, IgA, and IgM antibodies against ovalbumin, beta-lactoglobulin, and gliadin were measured in a series of 210 "allergy-risk" infants and their mothers. The antibody levels were determined with ELISA in sera obtained from mothers at delivery, and from their babies at birth, 6 weeks, 6 months, and 18 months. High levels of maternal IgG, IgA, or IgM antibodies to food at delivery did not appear to protect the baby against development of atopic disease. Maternal avoidance of cow's milk and egg during pregnancy had no significant influence on the level of food antibodies in cord blood, but the mother's intake of these foods during lactation affected the immunologic response of the baby, not only to these antigens but also to gliadin as well. Babies with minimal cow's milk exposure before 6 months had significantly lower levels of IgG to beta-lactoglobulin than babies regularly exposed to cow's milk. We conclude that maternal elimination diet during lactation influences the immunologic response of the baby, but if this prevents the development of atopic disease or just delays the immunologic maturation remains to be evaluated.

Binding of human colostral secretory IgA (SIgA) to Salmonella typhimurium 395 MR10 decreased the liability to hydrophobic interaction of the bacteria, as analysed by hydrophobic interaction chromatography on Octyl-Sepharose and partition in an aqueous polymer two-phase system consisting of dextran, poly(ethyleneglycol) (PEG) and poly-(ethyleneglycol)-palmitate (P--PEG). SIgA also reduced the negative charge of the bacteria. Treatment of the bacteria with centrifuged but not further fractionated colostrum added positive charge to the bacteria which was removed by treatment with pepsin. Colostral SIgA reduced the in vitro phagocytosis of S. typhimurium MR10 by polymorphonuclear leucocytes. The adhesion of the bacteria to cellulose membrane filters in the absence of phagocytes was also reduced after the interaction with SIgA. It is proposed that the binding of SIgA to bacterial surfaces has hydrophilic and anti-adhesive effects, which may serve to exclude antigen from mucosal surfaces.