ovalbumin and Celiac-Disease

We have shown that PLG nanoparticles loaded with peptide antigen can reduce disease in animal models of autoimmunity and in a phase 1/2a clinical trial in celiac patients. Clarifying the mechanisms by which antigen-loaded nanoparticles establish tolerance is key to further adapting them to clinical use. The mechanisms underlying tolerance induction include the expansion of antigen-specific CD4

Topics: Animals; Antigens; Antigens, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Celiac Disease; Cell Lineage; Epitopes, T-Lymphocyte; Glycoproteins; Humans; Immune Tolerance; Mice; Mice, Transgenic; Nanoparticles; Ovalbumin; Peptide Fragments; Peptides; Polylactic Acid-Polyglycolic Acid Copolymer; T-Lymphocytes, Regulatory; Viral Proteins

Intestinal reovirus infection can trigger T helper 1 (T

Topics: Administration, Oral; Animals; Caliciviridae Infections; Capsid Proteins; Celiac Disease; Diet; Disease Models, Animal; Female; HEK293 Cells; Humans; Immunity; Inflammation; Interferon Regulatory Factor-1; Lymph Nodes; Mice; Mice, Inbred C57BL; Norovirus; Ovalbumin; Th1 Cells; Virus Shedding

In celiac disease, enhanced permeability to gliadin peptides can result from their apico-basal transport by secretory immunoglobulin A1 (SIgA1) binding to the CD71 receptor ectopically expressed at the gut epithelial surface. Herein, we have established a mouse model in which there is apico-basal transport of the model antigen ovalbumin (OVA) by specific SIgA1 and have analyzed local T-cell activation. Transgenic DO11.10 mice were grafted with a hybridoma-secreting OVA-specific humanized IgA1, which could bind mouse CD71 and which were released in the intestinal lumen as SIgA. CD71 expression was induced at the gut apical surface by treating the mice with tyrphostin A8. Following gavage of the mice with OVA, OVA-specific CD4⁺ T cells isolated from the mesenteric lymph nodes displayed higher expression of the activation marker CD69 and produced more interferon gamma in mice bearing the hybridoma-secreting OVA-specific IgA1, than in ungrafted mice or in mice grafted with an irrelevant hybridoma. These results indicate that the protective role of SIgA1 might be jeopardized in human pathological conditions associated with ectopic expression of CD71 at the gut surface.

Topics: Animals; Antigens, CD; CD4-Positive T-Lymphocytes; Celiac Disease; Disease Models, Animal; Enterocytes; Female; Humans; Immunoglobulin A, Secretory; Intestinal Mucosa; Lymph Nodes; Mesentery; Mice; Mice, Transgenic; Ovalbumin; Protein Binding; Protein Transport; Receptors, Transferrin; Th1 Cells; Tyrphostins; Up-Regulation

CD4(+) T cells specific for dietary gluten and interleukin 15 (IL15) contribute to the pathogenesis of celiac disease. We investigated whether and how they interact to damage the intestine using mice that overexpress human IL15 in the intestinal epithelium and have CD4(+) T cells specific for ovalbumin, a dietary antigen.. We crossed mice with CD4(+) T cells specific for ovalbumin (OTII) with mice that overexpress human IL15 under an intestine-specific promoter (B6 × IL15Tge). The offspring (OTII × IL15Tge mice) received control or ovalbumin-containing diets until 3 months of age. Enteropathy was monitored by weight, ratio of villous:crypt length, and the number of intestinal lymphocytes. Phenotype, cytokine production, and degranulation of mucosal and spleen lymphocytes were analyzed by multicolor flow cytometry or enzyme-linked immunosorbent assay. Regulatory T-cell function and CD8(+) T-cell activation were analyzed in co-culture assays.. Exposure to ovalbumin reduced growth and led to enteropathy in OTII × IL15Tge mice but not in control OTII × B6 littermates. Enteropathy was associated with expansion of mucosal granzyme B(+) CD8(+) T cells, and developed despite increased frequency of functional ovalbumin-specific regulatory T cells. Ovalbumin-activated CD4(+) T cells secreted IL2, which along with IL15 stimulated expansion of noncognate intestinal cytotoxic CD8(+) T cells, which did not respond to regulatory T cells and induced epithelial damage.. We observed that in mice given food antigen, cooperation between IL15 and CD4(+) T cells is necessary and sufficient to activate CD8(+) T cells and damage the small intestine. We propose that this process is involved in the development of celiac disease.

Topics: Adoptive Transfer; Animals; Antigens; beta 2-Microglobulin; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Celiac Disease; Cell Degranulation; Cell Proliferation; Cells, Cultured; Coculture Techniques; Cytokines; Diet; Disease Models, Animal; DNA-Binding Proteins; Granzymes; Histocompatibility Antigens Class II; Humans; Immunity, Mucosal; Interleukin-15; Interleukin-2; Intestinal Mucosa; Intestine, Small; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Phenotype; Signal Transduction; Spleen; T-Lymphocytes, Regulatory

Activation of small intestinal gluten-reactive CD4(+) T-cells is a critical event in celiac disease. Deamidation of specific glutamine residues by tissue transglutaminase enhances the binding of T-cell activating gliadin epitopes to DQ2, increasing T-cell recognition. Our purpose was to investigate whether deamidated gliadin epitopes can be generated in the small intestinal mucosa by tissue transglutaminase and to characterize the location of the process. Intestinal explants from pig intestine and frozen biopsy slices from human and rat intestine were incubated with alpha-gliadin peptides containing the immunodominant motif. Monoclonal antibodies specifically recognizing the non-deamidated and/or the deamidated epitope were used for immunofluorescence studies. We conclude that endogenous tissue transglutaminase can mediate extracellular deamidation of gliadin peptides in the lamina propria. Gliadin peptides with more than one recognition site can be simultaneously cross-linked and deamidated extracellularly in the lamina propria, and might be of importance for the antibody response seen in untreated celiac disease patients.

Topics: Animals; Antibodies; Biopsy; Celiac Disease; Deamination; Disease Models, Animal; Duodenum; Gliadin; Glutens; Humans; Mucous Membrane; Ovalbumin; Peptides; Rats; Serum Albumin, Bovine; Swine; Transglutaminases

To investigate the humoral and cellular immune response against cow's milk proteins in Behçet's disease and to distinguish any behaviour during active or inactive disease.. Peripheral blood mononuclear cells from 16 patients and from eight normal controls were cultured in the presence of phytohaemagglutinin (PHA), beta-casein, beta-lactoglobulin, or chicken egg albumin. Interferon gamma (IFNgamma) and interleukin 4 (IL4) were measured in the culture supernatants by enzyme linked immunosorbent assay (ELISA). Serum samples from 46 patients with Behçet's disease and from 37 healthy subjects were also studied for antibody detection. Antibodies to beta-casein, beta-lactoglobulin, and chicken egg albumin were determined by ELISA.. High IFNgamma but not IL4 levels were found in the supernatants of lymphocytes from patients with active disease cultured in the presence of cow's milk proteins. Levels were comparable with those obtained in cultures stimulated with PHA. A significantly higher level of anti-beta-casein and anti-beta-lactoglobulin IgG and IgA antibodies was found in patients with active Behçet's disease. No relation was found between their occurrence and the age of the patients, the duration of disease, or the presence of gastrointestinal abnormalities. Antibodies to chicken albumin were detected at low levels and with a prevalence similar to that of healthy subjects.. The results indicate that an active immune response occurs in Behçet's disease. This response involves an increased frequency of antibodies to cow's milk protein and a strong Th1 polarisation after exposure to these antigens. The occurrence of these abnormalities supports a putative role for cow's milk proteins immune response in the pathogenesis of Behçet's disease.

Topics: Acute Disease; Adolescent; Adult; Aged; Animals; Antibodies; Behcet Syndrome; Case-Control Studies; Caseins; Cattle; Celiac Disease; Chickens; Crohn Disease; Female; Humans; Immunity, Cellular; Immunoglobulin A; Immunoglobulin G; Interferon-gamma; Interleukin-4; Lactoglobulins; Leukocytes, Mononuclear; Male; Middle Aged; Milk Proteins; Ovalbumin

Abdominal symptoms in the absence of mucosal abnormalities are features of both the irritable bowel syndrome (IBS) and latent/potential celiac disease (cd). To identify a possible subgroup of IBS patients with latent/potential cd, surrogate markers of cd were investigated in IBS patients.. IBS patients suffering from diarrhea (n = 102), and patients with active cd (n = 10), treated cd (n = 26), and latent cd (n = 5) were included in the study. We measured serum immunoglobulin (Ig) A against gliadin and tissue-transglutaminase, and IgA and IgM against gliadin, tissue-transglutaminase (intestinal cd-associated antibodies), and the dietary proteins beta-lactoglobulin and ovalbumin in duodenal aspirate by enzyme-linked immunosorbent assay. Intraepithelial lymphocytes (IELs) were counted in histology sections, and the expression of HLA-DQ2 (A1*0501/B1*0201) was investigated by polymerase chain reaction. In 26 IBS patients, the effect of 6 months of gluten withdrawal was examined.. Most cd patients expressed HLA-DQ2 and had increased intestinal cd-associated antibodies, whereas cd-associated serum IgA and IEL counts were increased in active cd in contrast to treated or latent cd. In IBS patients, 35% were HLA-DQ2-positive, 23% had increased IEL counts, and 0% and 30% had increased cd-associated antibodies in serum and duodenal aspirate, respectively. Furthermore, stool frequency and intestinal IgA decreased significantly under a gluten-free diet in the subgroups of HLA-DQ2-positive and intestinal antibody-positive IBS patients when compared with IBS patients without these markers.. HLA-DQ2 expression and increased intestinal cd-associated antibodies are markers that can identify latent/potential cd in a subgroup of IBS patients who consequently appear to profit from a gluten-free diet.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Antigens; Celiac Disease; Colonic Diseases, Functional; Diet; Duodenum; Female; Gliadin; Humans; Immunoglobulin A; Immunoglobulin M; Lactoglobulins; Male; Middle Aged; Ovalbumin; Reticulin; Transglutaminases

We compared the peptide binding specificity of three HLA-DQ molecules; HLA-DQ(alpha1(*)0501, beta1(*)0201), HLA-DQ(alpha1(*)0201, beta1(*)0202), and HLA-DQ(alpha1(*)0501, beta1(*)0301). The first of these molecules confers susceptibility to celiac disease and insulin-dependent diabetes mellitus, while the two latter molecules, which share either the alpha chain or the nearly identical beta chain with HLA-DQ(alpha1(*)0501, beta1(*)0201), do not predispose to these disorders. The binding of peptides was detected in biochemical binding assays as inhibition of binding of radiolabeled indicator peptides to affinity-purified HLA-DQ molecules. Binding experiments with several peptides demonstrated a clear difference in peptide binding specificity between the three HLA-DQ molecules. Further, single amino acid substitution analyses indicated that the HLA-DQ molecules have different peptide binding motifs. The experimental data were corroborated by computer modelling analysis. Our data suggest that the three HLA-DQ molecules prefer large hydrophobic residues in P1 of peptides with subtle differences in side-chain preferences. HLA-DQ(alpha1(*)0501, beta1(*)0201) and HLA-DQ(alpha1(*)0201, beta1(*)0202) both prefer large hydrophobic residues in P9, whereas HLA-DQ(alpha1(*)0501, beta1(*)0301) prefers much smaller residues in this position. HLA-DQ(alpha1(*)0501, beta1(*)0201) and HLA-DQ(alpha1(*)0201, beta1(*)0202), in contrast to HLA-DQ(alpha1(*)0501, beta1(*)0301), prefer negatively charged residues in P4 and P7. A less prominent P6 pocket also appears to differ between the three HLA-DQ molecules. Our results indicate that polymorphic residues of both the alpha and the beta chain determine the peptide binding specificity of HLA-DQ(alpha1(*)0501, beta1(*)0201), but that the beta chain polymorphisms appears to play the most important role. The information on peptide residues which are advantageous and deleterious for binding to these HLA-DQ molecules may make possible the prediction of characteristic features of peptide that bind to HLA-DQ(alpha1(*)0501, beta1(*)0201) and precipitate celiac disease.

Topics: Amino Acid Sequence; B-Lymphocytes; Binding Sites; Binding, Competitive; Celiac Disease; Cell Line, Transformed; Genes, MHC Class II; HLA-DQ Antigens; Humans; Models, Molecular; Molecular Sequence Data; Ovalbumin; Peptide Fragments; Polymorphism, Genetic; Static Electricity; Surface Properties

Serum antibodies IgA, IgG, and IgM against gliadin, ovalbumin, and beta-lactoglobulin were analyzed at the time of 228 small bowel biopsies in 116 celiac children. These were compared to the antibody levels at the time of biopsies performed in 199 children, where the biopsy discarded a clinical suspicion of celiac disease. For antibodies against gliadin, the enzyme-linked immunosorbent assay (ELISA) and diffusion-in-gel (DIG)-ELISA methods were compared. It was found that the combined information from IgA and IgG antigliadin antibodies gave the highest specificity (94%) and sensitivity (89%). The antibody responses to food antigens decreased with age in both celiac and reference children. The ELISA and DIG-ELISA methods gave comparable results and were equally efficient.

Topics: Adolescent; Aging; Antibodies; Antibody Specificity; Celiac Disease; Child; Child, Preschool; Diet; Diffusion; Enzyme-Linked Immunosorbent Assay; Gliadin; Glutens; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Infant; Lactoglobulins; Ovalbumin

Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha-lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy.

Topics: Adolescent; Adult; Aged; Antigens; Caseins; Celiac Disease; Edible Grain; Enzyme-Linked Immunosorbent Assay; Female; Food; Gliadin; Glycine max; Humans; Immunoglobulin A; Immunoglobulin G; Lactalbumin; Lactoglobulins; Male; Middle Aged; Ovalbumin

We have measured antibodies to gliadin (AGA), bovine beta-lactoglobulin, and chicken egg ovalbumin with a four-layer solid phase radioimmunoassay (RIA) in 62 children and adolescents with coeliac disease and in 36 healthy controls. The geometric mean titre of IgG AGA in patients at initial diagnosis was more than 100-fold that of controls (p less than 0.0001). Even patients on gluten-free diet had significantly higher IgG AGA titres than the controls (p = 0.0001), the difference being more than 5-fold. All the 42 patients with active disease (30 at initial diagnosis and 12 after gluten challenge) had their IgG AGA titre above 1,000, as compared with 2 (5.7%) of the 35 controls (p less than 0.0001). Both IgG and IgA AGA were quite sensitive and specific in identifying children with coeliac disease; the sensitivities for IgG and IgA AGA were 100% and 95.2%, the specificities 94.3% and 97.2%, respectively. We conclude that determination of IgG and IgA AGA with RIA is suitable for monitoring dietary compliance in children with coeliac disease, and the method is sensitive and specific for screening for coeliac disease in children.

Topics: Adolescent; Age Factors; Antibodies; Celiac Disease; Child; Child, Preschool; Evaluation Studies as Topic; Finland; Gliadin; Humans; Immunoglobulin G; Infant; Lactoglobulins; Mass Screening; Ovalbumin; Radioimmunoassay; Sensitivity and Specificity

In 47 children with coeliac disease, IgG1 was the dominant IgG subclass (mean 61%) in antibodies to gliadin, a protein component of wheat; IgG2 (22%) and IgG3 (15%) were also found. Very little IgG4 (3%) was detected. Both G2m(n)allotype and the age of the patient had an independent effect on the subclass distribution. The effects of these two factors seem similar to those described earlier on responses to polysaccharides; both G2m(n) and age increase the expression of IgG2 antibodies and concomitantly the share of IgG1 is decreased. The average increase in the share of IgG2 brought about by n/n-genotype was 25.3% (95% confidence limits 12.2-38.4%; P less than 0.001) and that brought about by each additional year of age of the patient 1.1% (0.3-1.9%; P = 0.006). IgG antibodies to beta-lactoglobulin and ovalbumin consisted mainly of IgG1 and IgG4. The titres of the IgG subclasses were low and in many cases below detection level. No association with G2m(n) genotype and share of IgG1 or IgG4 could be demonstrated. Age was inversely correlated with the shares of IgG1 in antibodies to beta-lactoglobulin and ovalbumin.

Topics: Adolescent; Adult; Aging; Analysis of Variance; Celiac Disease; Child; Child, Preschool; Dietary Proteins; Genotype; Gliadin; Humans; Immunodiffusion; Immunoglobulin G; Immunoglobulin Gm Allotypes; Infant; Lactoglobulins; Ovalbumin; Regression Analysis

Using a sensitive enzyme-linked immunoassay (ELISA), a significantly increased prevalence (p less than 0.001) of serum antibodies reactive with wheat gliadin, bovine milk or ovalbumin has been demonstrated in 75% (33/44) of adult patients with dermatitis herpetiformis (DH), compared with healthy adults. There was no significant difference in the prevalence of antibodies (79%) in patients on a gluten-free diet or not on a gluten-free diet (72%). These serum antibodies reactive with gliadin, milk and ovalbumin were of the IgG isotype. However, IgA anti-gliadin antibodies were also detected in DH patients, but only in patients who were not on a gluten-free diet. In contrast, IgA anti-milk antibodies were also detected in DH patients irrespective of whether the patient was on a gluten-free diet. In DH patients, antibodies reactive with ovalbumin were often restricted to the IgG4 subclass and antibodies reactive with bovine milk antigens (notably casein) were distributed predominantly in both IgG2 and IgG4 subclasses, a similar IgG isotype distribution to that observed in healthy individuals. However, anti-gliadin antibodies in DH patients showed no predominant IgG4 subclass restriction. IgG4 anti-ovalbumin antibodies and IgG4 and/or IgG2 anti-casein antibodies persisted for up to 4 yr without fluctuation, irrespective of whether DH patients were on a gluten-free diet.

Topics: Adult; Animals; Antigens; Celiac Disease; Dermatitis Herpetiformis; Dietary Proteins; Female; Gliadin; Glutens; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Male; Middle Aged; Milk; Ovalbumin; Triticum

In IgA glomerulonephritis (GN), the pathogenic role of IgA is well documented, but the specificity of these IgA is unknown. Cases of celiac disease associated with IgA GN have been reported and led us to investigate the role of gliadin sensitivity. We measured IgA, IgG and IgM antibodies to gliadin, beta-lactoglobulin and ovalbumin by ELISA (results expressed as optical density; OD) in 27 patients with primary IgA GN, 14 with membranous GN (MGN), 21 with idiopathic nephrotic syndrome (INS) and 21 healthy controls. The normal value for antigliadin IgA was less than 0.650 OD. 19/27 patients with IgA GN had a raised level versus 2/14 in MGN and 2/21 INS (p less than 0.001: IgA GN vs. MGN, INS and controls). Antibodies to beta-lactoglobulin were rarely found and were not more frequent in IgA GN. Cross-reactivity with reticulin was investigated in 16 patients who were serum-positive for IgA antigliadin: no reticulin antibodies were detected by immunofluorescence. Antigliadin IgA are of diagnostic value for distinguishing IgA GN from other GN, with a sensitivity of 70%, a specificity of 89%, a positive predictive value of 83% and a negative one of 79%.

Topics: Adult; Antibody Specificity; Celiac Disease; Dietary Proteins; Enzyme-Linked Immunosorbent Assay; Female; Food Hypersensitivity; Gliadin; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Lactoglobulins; Male; Ovalbumin; Plant Proteins

In this study we have investigated the possible effects of a local immune response on the intestinal permeability and morphology in rats. The animals were immunized subcutaneously by small doses of gliadin or ovalbumin. Immunization with gliadin led to small but significantly increased levels of IgA and IgM antibodies, similar to those reported for patients with coeliac disease. Immunization with ovalbumin gave significantly increased antibody levels of IgE, IgG, IgA and IgM. Subsequent antigen provocations by oral administration of gliadin (1 mg), together with fluorescein isothiocyanate-labelled dextran (molecular weight 3,000 daltons) as permeability marker, resulted in an increased intestinal permeability for this marker. This alteration of the intestinal permeability was qualitatively similar to that previously reported for patients with coeliac disease. Antigen provocation with ovalbumin caused a decreased permeability for both dextran and different-sized polyethylene glycols, but first at a dose of 40 mg. Direct antigen administration (gliadin or ovalbumin) into a ligated part of the ileum gave qualitatively similar but less pronounced permeability changes when compared with the effects obtained after oral administration of the respective antigen. However, neither gliadin nor ovalbumin challenge led to any ultrastructural changes of the intestinal wall. In summary, we have been successful in inducing specific antibody responses towards gliadin in rats and increased intestinal permeability upon gliadin provocation without any coexisting morphological alterations.

Topics: Animals; Celiac Disease; Female; Gliadin; Immunization; Immunoglobulins; Intestinal Mucosa; Intestines; Ovalbumin; Permeability; Plant Proteins; Rats; Rats, Inbred Strains

The uptake of ovalbumin (OA) from egg and beta-lactoglobulin (BLG) from cow's milk into the blood was investigated for seven hours after a test meal in five children with coeliac disease on a gluten free diet and after gluten challenge, and in five children with normal jejunal mucosa. Ovalbumin was detectable by ELISA in three of five coeliac children (maximal concentrations 8-178 ng/ml serum) and in five of five controls (maximal 4-91 ng/ml serum). Beta-lactoglobulin was detected in three of five coeliac children (maximal 0.6-6 ng/ml serum) and in two of five controls (maximal 0.5 and 50 ng/ml serum). No clear relationship was seen between maximal antigen concentrations and titres of serum IgG or IgA antibodies determined by ELISA, or as percentage antigen binding in a Farr type radioimmunoassay. Ovalbumin and beta-lactoglobulin was seen in serum of all coeliac patients and controls by HPLC fractionation in combination with ELISA, either in high MW fractions, or at the Mr of native OA and BLG, respectively. In one control degradation products (about 17 kD) of BLG were detectable in serum. The serum concentrations of OA and BLG were increased on gluten challenge in four or five coeliac children, indicating increased macromolecular passage through the gut mucosa in untreated coeliac disease.

Topics: Antibodies; Antigens; Celiac Disease; Child; Child, Preschool; Chromatography, High Pressure Liquid; Dietary Proteins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intestinal Absorption; Lactoglobulins; Male; Ovalbumin

Serum IgG antibodies reactive with different dietary proteins have been detected in a significant proportion of adult patients with coeliac disease, dermatitis herpetiformis and atopic eczema. Serum anti-milk antibodies were shown to be distributed predominantly between the IgG2 and IgG4 subclasses, whereas anti-gliadin antibodies in atopic eczema were predominantly of the IgG4 subclass. Furthermore, as antibodies to each of these dietary antigens in healthy adults were markedly restricted to the IgG4 subclass, their production may be part of a normal immune response to dietary proteins. There was no correlation between serum IgG4 antibody and total serum IgG4 level. In contrast, restricted IgG4 anti-gliadin antibodies were less prevalent in the serum of patients with coeliac disease and dermatitis herpetiformis, suggesting defective downstream switching of Ig heavy-chain genes in these conditions.

Topics: Celiac Disease; Dermatitis Herpetiformis; Dermatitis, Atopic; Dietary Proteins; Female; Food Hypersensitivity; Gliadin; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin Isotypes; Male; Milk Proteins; Ovalbumin

Antibodies to gliadin (AGA) were found in 77 (94%) of 82 sera from patients with active coeliac disease (untreated and after gluten challenge). Although IgG AGA had a higher nosological sensitivity than IgA AGA (88% versus 67%), their nosological specificity was lower than that of IgA antibodies (87% versus 100%). The sensitivity of antibodies to casein, beta-lactoglobulin, and ovalbumin in active coeliac disease varied from 36% to 48% without significant difference between IgG and IgA antibodies. IgG and IgA antibodies to milk and egg proteins showed a specificity similar to that of AGA, although some IgA antibodies other than AGA were found in disease controls (Crohn's disease, ulcerative colitis, post-enteritis syndrome).

Topics: Adolescent; Adult; Antibodies; Antigens; Caseins; Celiac Disease; Child; Child, Preschool; Dietary Proteins; Enzyme-Linked Immunosorbent Assay; Gliadin; Humans; Immunoglobulin A; Immunoglobulin G; Infant; Lactoglobulins; Middle Aged; Ovalbumin; Plant Proteins

IgG subclasses of antibodies to the dietary antigens gliadin, glycgli (a gluten component), ovalbumin (OA) and beta-lactoglobulin (BLG) were quantified in children with coeliac disease (CD), nine on a gluten-containing diet, 15 on a gluten-free diet, and in appropriate controls. In addition, total serum IgG subclasses were measured. IgG1 and IgG3 antibodies to gluten and glycgli were detected in 9/9 and 8/9 CD-patient on a gluten-containing diet, respectively, and in 4/15 and 6/15 patients on a gluten-free diet. None of the controls had appreciable levels of IgG1 antibodies and only 1/22 of the controls had IgG3 antibodies to gliadin and glycgli. IgG2 and IgG4 antibodies to the same antigens were found in a few coeliacs and controls. Consecutive samples from coeliac children (8 patients) showed a clear relation between the exposure to gluten and a rise in IgG1 (8/8) and IgG3 antibody levels (7/8). In contrast, IgG antibodies to OA and BLG were almost exclusively of the IgG1 and IgG4 subclasses. The highest levels were found in children with CD, but the differences between the groups were not significant. Total serum IgG subclasses did not differ between the groups, but the IgG2 and IgG4 levels in most coeliac children were low. The production of IgG1 and IgG3 antibodies to gluten components may be an important precondition for the development of coeliac disease in susceptible individuals.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Gliadin; Glutens; Humans; Immunoglobulin G; Lactoglobulins; Ovalbumin; Plant Proteins

We report six patients with coeliac disease in whom arthritis was prominent at diagnosis and who improved with dietary therapy. Joint pain preceded diagnosis by up to three years in five patients and 15 years in one patient. Joints most commonly involved were lumbar spine, hips, and knees (four cases). In three cases there were no bowel symptoms. All were seronegative. X-rays were abnormal in two cases. HLA-type A1, B8, DR3 was present in five and B27 in two patients. Circulating immune complexes showed no consistent pattern before or after treatment. Coeliac disease was diagnosed in all patients by jejunal biopsy, and joint symptoms in all responded to a gluten-free diet. Gluten challenge (for up to three weeks) failed to provoke arthritis in three patients tested. In a separate study of 160 treated coeliac patients attending regular follow up no arthritis attributable to coeliac disease and no ankylosing spondylitis was identified, though in a control group of 100 patients with Crohn's disease the expected incidence of seronegative polyarthritis (23%) and ankylosing spondylitis (5%) was found (p less than 0.01). Arthritis appears to be a rare manifestation of coeliac disease. This relationship may provide important clues to the role of gastrointestinal antigens in rheumatic diseases.

Topics: Adolescent; Adult; Antibodies, Anti-Idiotypic; Antigen-Antibody Complex; Arthritis, Rheumatoid; Celiac Disease; Female; Gliadin; Hand; Humans; Male; Middle Aged; Ovalbumin; Radiography; Reticulin

Serum IgG, IgA and IgM activities to wheat, egg and cow's milk antigens were measured by an ELISA method in children and adults with coeliac disease (CD). In untreated patients, the IgA activity was characteristically raised to gluten antigens but often also to proteins from egg or cow's milk. Setting the upper reference range for gluten antibodies as the highest IgA reading obtained in healthy controls and patients with other intestinal disorders, IgA measurements afforded virtually 100% diagnostic sensitivity and specificity and detected 94% of children and 80% of adults with untreated CD. Such measurements, therefore, represent a valuable adjunct in the diagnosis of this disease. IgA activity to beta-lactoglobulin, casein or ovalbumin higher than the normal 95 percentile was found in 44-89% of untreated patients. Reduction of these antibody titres seemed to reflect relatively well the response to treatment with a gluten free diet, particularly the activity to beta-lactoglobulin. Monitoring of IgA antibodies to dietary antigens other than gluten may therefore be of particular importance in the follow-up of CD patients.

Topics: Adolescent; Adult; Aged; Antigens; Celiac Disease; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Glutens; Humans; Immunoglobulins; Infant; Intestinal Diseases; Male; Middle Aged; Milk Proteins; Ovalbumin

Serum concentrations of ovalbumin, beta-lactoglobulin, and antigen-antibody complexes were measured after jejunal administration of milk and raw egg in 6 children with active coeliac disease and in 4 controls. The results did not support the hypothesis of a generalised increase in absorption of antigens from the intestinal lumen in coeliac disease.

Topics: Antigen-Antibody Complex; Antigens; Celiac Disease; Child; Humans; Intestinal Absorption; Lactoglobulins; Ovalbumin

Topics: Animals; Celiac Disease; Chromatography, Gel; Glutens; Glycoproteins; Humans; Intestine, Small; Kinetics; Lectins; Membrane Proteins; Microvilli; Molecular Weight; Ovalbumin; Rats

Topics: Antibodies; Celiac Disease; Child, Preschool; Cromolyn Sodium; Food Hypersensitivity; Humans; Immunoglobulin G; Infant; Intestinal Absorption; Malabsorption Syndromes; Ovalbumin

Topics: Antibodies; Celiac Disease; Child; Dietary Proteins; Geriatrics; Glutens; Humans; Immunodiffusion; Milk; Ovalbumin; Precipitin Tests; Statistics as Topic