Mucosal T lymphocytes in human colonic schistosomiasis: relationship to MHC antigens.
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Biomedical subjects
Publications and source records attributed to R V Heatley.
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Biopsy specimens of gastric and duodenal mucosa from 290 patients were examined histologically for metaplasia and Campylobacter pyloridis. Estimates of pH on samples of fasting gastric juice from 55 of the patients were performed, and mucosal biopsy specimens from 33 patients were also cultured for C pyloridis. Active duodenitis was seen in 34 duodenal biopsy specimens. Thirty (88%) of the patients with active duodenitis had both greater than 5% gastric metaplasia in the duodenal specimen and C pyloridis associated gastritis. These two factors coexisted in only 0.43% of patients with no duodenal inflammation. When C pyloridis were seen histologically in duodenal biopsy specimens they were confined to areas of gastric metaplasia and never occurred in the absence of a polymorph infiltrate. Of the 55 patients with measurements of gastric juice pH, gastric metaplasia was present in the duodenum in 20 of 42 with a pH of less than 2.5, and in 0 of 13 with a pH of greater than 2.5. These results suggest that acid induced gastric metaplasia in the duodenum and C pyloridis associated gastritis may be synergistic in the pathogenesis of duodenitis; the metaplastic gastric epithelium allows C pyloridis to colonise the duodenal mucosa, where it produces an acute inflammatory response.
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In vitro immunoglobulin secretion has been studied using isolated colonic mucosal lymphoid cell populations obtained from 41 patients with non-inflammatory intestinal disease. Cell fractions were separated into intra-epithelial and lamina propria-enriched populations. The secretion of immunoglobulins by mucosal cells appeared to be independent of mitogen stimulation. When intra-epithelial lymphocyte preparations were co-cultured with autologous lamina propria lymphocytes, the secretion of IgM was significantly depressed but that of IgA and IgG was preserved. Co-cultured of mucosal cells with autologous peripheral blood lymphocytes resulted in suppression of pokeweed mitogen stimulated and unstimulated immunoglobulin secretion. Lamina propria T cells were shown to provide helper function for the in vitro secretion of IgA and IgM but not IgG, by autologous peripheral blood B cells. Immunoglobulin secretion by lamina propria lymphocytes was shown to be partly dependent on the concentration of E-rosette forming cells. These experiments demonstrate that human colonic mucosal lymphoid cells contain specific populations of helper and suppressor cells which selectively control intestinal immunoglobulin secretion.
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Antibody titres to Campylobacter pyloridis in serum and gastric juice were estimated by an enzyme linked immunosorbent assay (ELISA) to whole organisms obtained from bacterial culture in 39 patients with non-ulcer dyspepsia. Whereas 20 of the 21 patients with chronic gastritis had gastric C pyloridis, 17 patients with no C pyloridis had normal histology in the gastric antrum and body. Significantly raised serum IgG and IgA antibody titres to C pyloridis were found in colonised patients with gastritis. Patients with raised IgG antibody to C pyloridis were also shown to have significantly raised titres to other Campylobacter species, suggesting antigenic cross reactivity. Gastric juice antibodies were also studied and IgA titres to C pyloridis were detected in a proportion of patients with gastritis, together with low levels of IgM, but no IgG.
Nutrient depletion is a common complication of inflammatory bowel disease, and some of the consequences can be severe. Although it is often easy to recognise the most severely undernourished subjects, those with lesser degrees of malnutrition may prove more difficult to detect. Measurements of many nutritional variables will be abnormal in patients with inflammatory bowel disease, especially in those with Crohn's disease, but are not always relevant to the clinical management of patients. Anthropometric means of assessment, in particular, measurement of mid arm circumference, can act as a simple, reproducible method of detecting those most at risk of appreciable undernutrition.
Colonising Campylobacter pyloridis were identified histologically in gastric biopsy specimens from 89% of 83 patients with non-ulcer dyspepsia and chronic gastritis, but not in 58 dyspeptic patients with normal mucosa. The presence and population density of organisms was associated with the presence of intraepithelial neutrophils. In vivo coating of the organisms by host immunoglobulin was investigated by immunoperoxidase staining of IgA, IgG, and IgM in 54 biopsy specimens. IgA coated bacteria were seen in all cases of active gastritis, and in 60% of biopsy specimens without intraepithelial neutrophils. Coating with IgG or IgM, or both, was correlated with activity of gastritis and was rarely seen in the absence of a neutrophil infiltrate.
The clinical features and results of standard laboratory investigations have been studied in children with cows' milk protein intolerance and the results compared with an in vitro test, examining the degranulation of peripheral blood basophils to cows' milk antigen. Of 67 children investigated, 26 had probable intolerance to cows' milk, and maximal basophil degranulation responses in these children were significantly increased (p less than 0.01). The most striking differences were those observed between children with definite cows' milk protein intolerance and control individuals (p less than 0.002). Of 14 children with definite cows' milk intolerance clinically, only 4 had negative responses. The basophil degranulation test may be a valuable, simple and inexpensive investigation in the diagnosis of cows' milk protein intolerance and perhaps also in other conditions in which food sensitivity plays a part.
IgE production by peripheral blood lymphocytes (PBL) and rectal mucosal biopsies in vitro has been examined in patients with ulcerative colitis (UC) and Crohn's disease (CD). The degranulation of peripheral blood basophils to food antigens has also been investigated in these patients. Mitogen-induced IgE production was reduced in patients with UC, but enhanced in PBL cultures from patients with CD. Increased numbers of basophils degranulated in the presence of cows' milk in UC patients, but normal responses occurred in patients with CD. This evidence supports the suggested role of IgE-mediated mechanisms involving mast cell/basophil interactions in the pathogenesis of inflammatory bowel disease.
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Forty patients with Crohn's disease were divided into undernourished (18) and well nourished (22) groups depending on whether their midarm circumference was below or above 90% of the ideal standard. Plasma 25-(OH)D3 and the dihydroxylated metabolites, 24,25-(OH)2D3 and 1,25-(OH)2D3 were measured in the summer. Results were related to clinical and biochemical parameters and also compared with results from patients with ulcerative colitis and healthy subjects who served as controls. Plasma 25-(OH)D3 was reduced in the undernourished Crohn's group compared with the well nourished Crohn's group, who did not differ from the controls. Over 50% of the undernourished Crohn's group had evidence of secondary hyperparathyroidism and raised alkaline phosphatase concentrations, although concentrations of 1,25-(OH)2D3 were normal. The low 25-(OH)D3 concentrations related to disease activity. It is suggested that undernourished Crohn's patients who have high levels of disease activity are at risk of vitamin D deficiency, and attempts should be made to improve their vitamin D nutrition.
An imbalance in immunoregulatory cells might explain the increase in autoimmune phenomena associated with hyposplenism. Using the monoclonal antibodies OKT3, OKT4 and OKT8 to identify T-lymphocyte subsets, we have studied 19 patients with treated coeliac disease, 9 of whom had hyposplenism, 10 splenectomized subjects, 10 gastrointestinal control patients and 10 normal subjects. There was no significant difference in the proportion of lymphocytes, OKT3+, OKT4+ or OKT8+ cells, nor in the OKT4+/OKT8+ ratio, between any of the patient groups and normal or control subjects. Splenectomized subjects had higher total lymphocyte counts than normals (p less than 0.01). Hyposplenic coeliac patients had higher total lymphocyte counts than other coeliacs (p less than 0.05). Hyposplenic coeliac patients and splenectomized subjects tended to have an increase in the absolute number of OKT8+ cells, which in the latter group was statistically significant (p less than 0.05). We conclude that the increased frequency of autoimmune phenomena associated with hyposplenism due to coeliac disease or after splenectomy is not the result of an altered ratio of OKT4+/OKT8+ cells or a deficiency of OKT8+ cells.