Celiac Disease Mucosa Research Articles

Small intestinal mucosa in coeliac disease and cow's milk protein intolerance: morphometric and immunofluorescent studies.

One hundred and twenty-five small intestinal biopsies from children with coeliac disease (CD), cow's milk protein intolerance (CMPI) and controls were compared by morphometric analysis, by counting intraepithelial lymphocytes (IEL) and by quantitative evaluation of immunoglobulin-containing cells of lamina propria. The double-stain immunofluorescent technique of Brandtzaeg and Baklien [2] was used, based on defined mucosal tissue units. A patchy enteropathy was found in 60% of CMPI, and in 14% of nonspecific changes, but never in CD. There was a significant difference in crypt depth between CD (360 +/- 80 microns) and CMPI (217 +/- 92 microns), even when lesions of equal grade were compared (P less than 0.015). IEL counts per 1000 epithelial cells showed even better discrimination between the groups (CD: 793 +/- 173, CMPI: 320 +/- 143, P less than 0.001). In CD, there was a relatively greater increase of IgM-cells (X 4.9) and of IgG-cells (X 4.2) than of IgA-cells (X 2.6). Ig-cell changes outlasted the morphological lesion in CD on a gluten-free diet. In CMPI, IgM-cells (X 2.3), IgG-cells (X 2.5), and IgA-cells (X 1.7) were proportionately increased, compared to controls. A special increase of IgE-cells in CMPI could not be substantiated. By computerized stepwise discriminant analysis based upon crypt depth, villus/crypt-ratio, IEL-count, and counts of IgM-, IgG-, IgA-containing cells of lamina propria, accurate classification of patient groups was accomplished, even when only the initial biopsy data were analysed.

Cell-mediated immunity to gluten within the small intestinal mucosa in coeliac disease.

Jejunal biopsies from controls and coeliac patients were maintained in organ culture in the presence of gluten fraction III. The culture media were assayed for evidence of lymphokine activity in a migration inhibition test using normal peripheral blood leucocytes. Significant inhibition of migration was produced by media from untreated coeliac patients compared with controls (P less than 0.005) or treated coeliac patients (P less than 0.001), indicating the production of a leucocyte migration inhibition factor (LIF) by untreated coeliac mucosa in response to gluten fraction III. The degree of inhibition correlated with the preculture interepithelial lymphocyte count in the coeliac biopsies (P less than 0.02). In six coeliac patients studied when on a normal diet and on a gluten-free diet, LIF was produced while on a normal diet, but not while on a gluten-free diet. These results suggest that a local cell-mediated immune reaction to gluten is present in the mucosa of patients with untreated coeliac disease but that this is reversed by treatment with a gluten-free diet.

Labelling indices after 3H-thymidine incorporation during organ culture of duodenal mucosa in coeliac disease.

Incorporation of 3H-thymidine during organ culture of duodenal biopsy specimens from 34 coeliac and 10 non-coeliac patients was studied by autoradiography. High labelling indices were found in flat, coeliac mucosas. Gluten fractions, which provoked histological deterioration during culture, induced labelling of a greater proportion of crypt cells and higher migration rate than parallelly cultured specimens on gluten-free medium. No influences on crypt cell kinetics could be observed after culture with gluten fractions incapable of producing histological damage or with alpha-lactalbumin. In coeliac remission mucosas, labelling indices were at the same level as in non-coeliac biopsies, and no significant effects of gluten were observed. Autoradiography seems to be a fairly sensitive and reliable determinant of gluten toxicity by organ culture in coeliac disease and should supplement the histological appraisal of the biopsies. The increment of labelling indices provoked by gluten exposure seemed not merely to be a consequence of increased desquamation of cells from the biopsy surface but could imply a direct influence of gluten on crypt cell kinetics in coeliac disease.

Semi-quantitative analysis of immunoglobulins and complement fractions 3 and 4 in the jejunal mucosa in coeliac disease and in food allergy in childhood. Immunohistochemical study by light and electron microscopy.

Immunoglobulins A, M, G and E and complement fractions 3 and 4 in jejunal biopsy specimens of 14 children were stained by the peroxidase-labelled antibody technique and studied in light and electron microscopy. In addition, cryostat sections were stained with FITC-conjugated anti-C3,-C4 and -IgE sera. Five patients had coeliac disease, three intestinal cow's milk or rye allergy, three eczema due to food allergy, and in three patients, who served as controls, intestinal and immunological diseases were excluded. This study showed that increased amounts of IgA and IgM both in coeliac disease and in food allergy are produced by the plasma cells in the lamina propria of the jejunum and are secreted into the gut through the epithelial cells in a similar manner as in the morphologically normal intestine. The amount of IgG produced locally or derived from serum, was increased in coeliac disease. IgE-producing cells were rare in all patients. No deposits of complement were seen in the basement membranes or epithelial cells.

Immunoglobulins in Jejunal Mucosa and Serum from Patients with Adult Coeliac Disease

Immunoglobulin (Ig)-containing cells were quantitated immunohistochemically in biopsy specimens from the proximal jejunal mucosa. The numbers of IgA, IgM, and IgG immunocytes in a defined "mucosal tissue unit" were, on the average, raised 2.4, 4.6, and 6.5 times, respectively, when 13 adult patients with untreated coeliac disease (CD) were compared with 15 patients who had a histologically normal mucosa. The IgA-:IgM-:IgG-cell ratios averaged 66:28:6 in untreated CD and 79:18:2.6 in the controls. Similar quantitative data in 10 patients with treated CD were intermediate. IgD- and IgE-containing cells were rare in all patient groups. Most patients in a heterogeneous malabsorption group showed a jejunal Ig-containing cell population similar to that seen in CD, indicating that the local immunocyte pattern may not be specific for the latter disease. The only significant alteration in serum Ig levels related to CD was a raised concentration of IgA compared with normal. This was consistent with the increased amounts of extracellular IgA revealed in the mucosa. However, there was no indication of a defect in the transport of dimeric IgA and IgM through SC-producing cells, which in the CD mucosa were present in both crypt and surface epithelium.

Identifying toxic fractions of wheat gluten and their effect on the jejunal mucosa in coeliac disease.

THE TOXICITY OF THREE FRACTIONS (A, B, AND C) OBTAINED BY ULTRAFILTRATION OF A PEPTIC: tryptic digest of gluten has been assessed by serial feeding experiments in patients with treated coeliac disease. The first fraction (A), which contains amino acids and oligopeptides, produced no damage to the jejunal mucosa. The other two fractions (B and C) both caused mucosal damage. Fraction B, which contains the products of digestion of smaller molecular weight, consists of polypeptides which are concentrated in the region of 8000 molecular weight. It contains no gliadin (molecular weight 50 000) or gluten. Ultrastructural evidence of damage was visible six hours after challenge with fraction B and by 10 hours histological abnormalities were also present. Ultrastructural abnormalities occurred early in the epithelial cells and preceded changes in the basement membrane and capillaries. The disaccharidases showed a pronounced depression in all three subjects by 24 hours. The rapid onset of damage after challenge, coupled with the evidence of recovery as soon as 72 hours later, is more in keeping with a direct action on the surface epithelial cells rather than an immune mechanism.

Small gut mucosal activities of pyrimidine precursor enzymes in celiac disease

Summary The increased mitotic cell count in the small intestinal mucosa in celiac disease has given rise to question as to whether increased cell turnover or prolonged mitosis were occurring. Two enzymes in the pyrimidine biosynthetic pathway, aspartate carbamoyl transferase and dihydroorotate dehydrogenase, have been measured in rat and human intestinal mucosa. Activities of aspartate carbamoyl transferase in normal mucosa obtained at surgery were 247 ± 114 nmoles per g per min. No inhibition of activity of this enzyme was noted after addition of cytidine mono-, di-, or triphosphate. Dihydroorotate dehydrogenase activity was 18.1 ± 9.2 nmoles per g per min from intestinal mucosa obtained at surgery. Peroral biopsy samples from normal subjects showed aspartate carbamoyl transferase activity of 282 ± 142 nmoles and dihydroorotate dehydrogenase activity of 9.9 ± 8.6 nmoles per g per min. Mucosa obtained from patients with celiac disease snowed normal or elevated enzyme activities; the more severe lesions showed the higher levels. These results provide indirect evidence to support increased cell turnover rather than maturation arrest in mitosis in the small intestinal epithelial cells in celiac disease.

Histological changes in the duodenal mucosa in coeliac disease. Reversibility during treatment with a wheat gluten free diet.

Histological changes in the duodenal mucosa in coeliac disease. Reversibility during treatment with a wheat gluten free diet.