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Kinetics of mucosal granulocyte activation after gluten challenge in coeliac disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Reumatologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Gastro)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Klinisk kemi)
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2005 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, no 6, 662-669 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To elucidate the dynamics of the rectal inflammatory response to rectal gluten challenge in coeliac disease by measuring inflammatory mediators released by activated neutrophils, eosinophils and mast cells/basophils.

MATERIAL AND METHODS: The release of myeloperoxidase (MPO), eosinophilic cationic protein (ECP) and histamine was measured continuously during the early challenge period (3-6 h after gluten challenge) in coeliac patients (n = 9) and healthy controls (n = 5). A segmental perfusion technique was used to carry out this part of the study. Another method, the mucosal patch technique, was used to enable studies of the late challenge period (5-48 h after gluten challenge) in coeliac patients (n = 10) and healthy controls (n = 15).

RESULTS: During the early challenge period the MPO levels began to increase as early as 3 h after challenge and increased progressively (p < 0.001) during the next 3 h. A decline in MPO levels was seen 15 h after challenge and another phase of increasing levels at 24 h. The MPO values declined 48 h after challenge but still remained significantly increased (p < 0.05). The ECP levels started to increase 4 h after challenge and increased progressively during the next 2 h (p < 0.05). The ECP kinetics during the late challenge period was similar as for MPO but the relative increase in ECP was more modest. No increase in histamine was found except in one patient who had a transient, early increase of histamine (3-5 h after challenge). No signs of inflammatory reaction to gluten were seen in the controls.

CONCLUSIONS: There is a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation is apparent 4 h after challenge and remains for at least 48 h. A more modest eosinophil activation defined by ECP levels starts 1-2 h later and also remains for at least 48 h. The biphasic pattern of MPO and ECP after challenge suggests a biphasic inflammatory reaction.

Place, publisher, year, edition, pages
2005. Vol. 40, no 6, 662-669 p.
Keyword [en]
Adult, Aged, Case-Control Studies, Celiac Disease/*diagnosis, Comparative Study, Eosinophil Granule Proteins/analysis/*metabolism, Female, Gluten/*diagnostic use/*pharmacokinetics, Granulocytes/*drug effects, Humans, Inflammation Mediators/analysis/metabolism, Intestinal Mucosa/drug effects, Kinetics, Male, Middle Aged, Neutrophil Activation, Probability, Prognosis, Reference Values, Research Support; Non-U.S. Gov't, Risk Factors, Sensitivity and Specificity, Severity of Illness Index
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-93625PubMedID: 16036526OAI: oai:DiVA.org:uu-93625DiVA: diva2:167158
Available from: 2005-10-20 Created: 2005-10-20 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Food Antigen Sensitivity in Coeliac Disease Assessed by the Mucosal Patch Technique
Open this publication in new window or tab >>Food Antigen Sensitivity in Coeliac Disease Assessed by the Mucosal Patch Technique
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A diagnosis of coeliac disease (CD) in adults relies on the presence of a structurally abnormal intestinal mucosa, followed by a clear clinical remission on a gluten-free diet. There is a clear need for a rapid, simple, safe and sensitive method to determine the type and intensity of inflammation in the gut mucosa in clinical practice. The overall aims of our studies were to develop and evaluate a new technique, “the mucosal patch technique”, to characterize rectal local inflammatory process after rectal food challenge in patients with CD. In study 1 we evaluated the potential of the new technique. The technique was well tolerated and easily applied. Pronounced neutrophil and eosinophil involvement in ulcerative colitis (UC) was demonstrated. With the high sensitivity of the technique, low-degree mucosal neutrophil activation could also be quantified in patients with collagen colitis,UC in clinical remission and in patients with irritable bowel syndrome. In study 2 and 3 the aim was to elucidate the dynamics of the rectal inflammatory response and nitric oxide (NO) production after rectal gluten challenge. We found a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation was apparent 4 hours after challenge and remains for at least 48 hours. A more modest eosinophil activation started 1-2 hours later and remained at least for 48 hours. The biphasic pattern of neutrophil and eosinonphil activation after challenge suggests a biphasic inflammatory reaction. The activation of neutrophils and eosinophils precedes a pronounced enhancement of mucosal NO production. Some of our coeliac patients displayed signs of an inflammatory reaction after rectal corn gluten challenge. In study 4 the aim was to investigate the local inflammatory reaction to gluten and cow’s milk protein in CD patients in remission. The findings indicate that not only gluten sensitivity but also cow’s milk (CM) protein sensitivity is common in CD. The data support the hypothesis that CM sensitivity may contribute to persistent symptoms in coeliac patients on gluten-free diet.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 80
Keyword
Medicine, Coeliac disease, Diagnostic instrument, food hypersensitivity, gut pathophysiologi, inflammation, nitric oxide, rectal instillation, gluten, corn, milk hypersensitivity, inflammatory bowel disease, irritable bowel syndrome, Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-6020 (URN)91-554-6374-6 (ISBN)
Public defence
2005-11-11, Grönwallssalen, Uppsala Akademiska Sjukhus, Uppsala, 09:15
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Available from: 2005-10-20 Created: 2005-10-20Bibliographically approved

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Venge, PerHällgren, Roger

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