Mast cell tryptase levels in gut mucosa in patients with gastrointestinal symptoms caused by food allergy.

BACKGROUND AND AIMS: Mast cells, which are important effector cells in food allergy, require a special histologic treatment for quantification in endoscopic gastrointestinal samples. The objective of this study was to investigate whether mast cell tryptase (T), a typical mast cell-associated marker, may help to detect patients with food allergy. METHODS: Mast cell T was investigated from 289 colorectal samples of 73 controls, 302 samples from 43 patients with food allergy and gastrointestinal symptoms, and 72 samples from 12 patients with partial or complete remission of allergic symptoms. Endoscopically taken samples were immediately put into liquid nitrogen, mechanically homogenized by a micro-dismembrator with three homogenization steps and tissue T content (ng T/mg wet weight) was measured by fluoroenzyme immunoassay. RESULTS: Tissue T levels from the lower gastrointestinal tract were significantly elevated (p < 0.0001) in patients with manifest gastrointestinal allergy (median: 55.7, range: 9.3-525.0) compared with controls (median: 33.5, range: 8.0-154.6). A subgroup of 12 patients with remission of allergy showed markedly decreased symptom scores and mucosal T levels after more than 1 year of antiallergic therapy (pretreatment median: 54.1, range: 37.0-525.0 and posttreatment median: 28.4, range: 19.8-69.1; p = 0.01). CONCLUSIONS: High T levels in the gut of food-allergic patients support the role of stimulated mast cells or an increased mast cell number.

Analysis of immediate ex vivo release of nitric oxide from human colonic mucosa in gastrointestinally mediated allergy, inflammatory bowel disease and controls.

Nitric oxide (NO) is a local mediator in inflammation and allergy. The aim of this study was to investigate whether live incubated colorectal mucosal tissue shows a direct NO response ex vivo to nonspecific and specific immunological stimuli and whether there are disease-specific differences between allergic and chronic inflammatory bowel disease (IBD). We took biopsies (n=188) from 17 patients with confirmed gastrointestinally mediated food allergy, six patients with inflammatory bowel disease, and six control patients. To detect NO we employed an NO probe (WPI GmbH, Berlin, Germany) that upon stimulation with nonspecific toxins (ethanol, acetic acid, lipopolysaccharides), histamine (10(-8)-10(-4)M), and immune-specific stimuli (anti-IgE, anti-IgG, known food allergens) directly determined NO production during mucosal oxygenation. Non-immune stimulation of the colorectal mucosa with calcium ionophore (A23187), acetic acid, and ethanol induced a significant NO release in all groups and all biopsies. Whereas, immune-specific stimulation with allergens or anti-human IgE or -IgG antibodies did not produce significant release of NO in controls or IBD. Incubation with anti-human IgE antibodies or allergens produced a ninefold increase in histamine release in gastrointestinally mediated allergy (p<0.001), but anti-human IgE antibodies induced NO release in only 18% of the allergy patients. Histamine release in response to allergens or anti-human IgE antibodies did not correlate with NO release (r(2)=0.11, p=0.28). These data show that nonspecific calcium-dependent and toxic mechanisms induce NO release in response to a nonspecific inflammatory signal. In contrast, mechanisms underlying immune-specific stimuli do not induce NO production immediately.

The measurement of leukotrienes in urine as diagnostic option in systemic mastocytosis.

Clinical symptoms of patients with mastocytosis may include skin reactions, but also gastrointestinal symptoms with hyperacidity and dysmotility (e.g. ulcer, diarrhea, pain). They are mostly caused by mediators derived from activated mast cells. In order to investigate the impact of leukotrienes on the clinical symptoms excretion of leukotriene B4 (LTB4) and leukotrienes C4-D4-E4 (cysteinyl-leukotrienes) into urine was studied in 9 patients with indolent systemic mastocytosis divided into a group with high and low intensity of symptoms and in 11 healthy volunteers. Leukotriene excretion was determined by ELISA and correlated with methylhistamine excretion. Patients with systemic mastocytosis with high and low intense symptoms showed significantly higher urinary excretion of cysteinyl-leukotrienes than controls. There was a positive correlation of cysteinyl-leukotriene excretion and urinary methylhistamine excretion. LTB4 excretion was also significantly increased in patients with systemic mastocytosis compared to healthy volunteers. No correlation of urinary LTB4 excretion with urinary methylhistamine was observed. The present study demonstrates that urinary excretion of LTB4 and cysteinyl-leukotrienes LTC4-D4-E4 is clearly enhanced in indolent systemic mastocytosis Hence, determination of leukotriene excretion into urine can be used as a tool in the diagnostic and in the therapeutic monitoring of systemic mastocytosis.

Clinical significance of lymphoid hyperplasia of the lower gastrointestinal tract.

Lymphoid hyperplasia of the intestine has been associated with multiple diseases and symptoms. This study was undertaken to analyze the number and topographical distribution of the lymphoid follicles. A total of 302 adult consecutive patients were enrolled when they underwent elective colonoscopy. Standardized pictures from terminal ileum and colon were taken using video colonoscopes. In each picture, the number, size, and mucosal elevation of lymphoid follicles were analyzed in relation to histological and immunological findings and medical history. Lymphoid hyperplasia was found to be most extensive in the terminal ileum and cecum. Patients with untreated gastrointestinally mediated allergy (GMA) showed the highest number of lymphoid follicles per visible field in the terminal ileum ( P < 0.001) and cecum ( P = 0.003) vs. the control group. Patients with infectious colitis also showed a high number of lymphoid follicles per endoscopic visible field in the transverse colon ( P = 0.020). The presence of lymphoid hyperplasia is a frequent finding during colonoscopy. It may indicate an enhanced immunological mucosal response to antigenic stimulation such as GMA or infection.