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To characterize circulating DC subsets from healthy controls and IBD patients and to assess, following an ex vivo challenge, the effect of anti-TNF (infliximab, adalimumab and golimumab), anti-p40 -IL-12/IL-23- (ustekinumab) and anti-α4β7 (vedolizumab) immunomodulators on both the GI production of soluble immune mediators and the mucosal capacity to alter the recruitment capacity of circulating DC subsets. It is expected that such approach will provide further information on the action mechanisms of such therapies on IBD patients, allowing a better understanding of the pathophysiology of this disease and the identification of tissue-specific therapeutic targets, thus avoiding collateral problems associated with systemic immunomodulation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non-inflamed |
| ||
| Inflamed ulcerative colitis |
| ||
| inflamed Crohn´s disease |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab | Biological | Ex-vivo conditioning of lamina propria and peripheral blood mononuclear cells. Here, we will address whether the current available biological therapies for IBD patients (infliximab, golimumab, adalimumab, vedolizumab and ustekinumab) elicit a differential effect on the mucosal capacity to recruit circulating leukocytes on an ex-vivo approach using transwell culture systems. |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of biological drugs on the secretion of gut-chemoattractants by the intestinal mucosa | To assess, ex-vivo, the capacity of the IBD mucosa to recruit subsets of circulating leukocytes following mucosal conditioning with biological drugs. | 18 months |
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Inclusion Criteria:
Patients with active IBD, and endoscopic and histological diagnosis of CD or UC that attend a colonoscopy with sedation performed by medical criteria.
Patients without an IBD diagnosis, or other types of inflammatory, allergic, malignant or autoimmune diseases, prior to their inclusion in this project. All patients will attend a colonoscopy with sedation at medical judgment with biopsy indication for histopathological study as in cases of diarrhea but also due to changes in the bowel transit, rectal bleeding or screening for gastrointestinal diseases. Patients will be paired in age and gender with the IBD groups. All patients will have no signs of macroscopic or microscopic inflammation hence excluding the presence of microscopic colitis.
Exclusion Criteria:
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healthy controls and patients with active inflammatory bowel disease (ulcerative colitis and Crohn´s disease).
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Cell culture supernatants
|
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D000069285 | Infliximab |
| C529000 | golimumab |
| D000068879 | Adalimumab |
| C543529 | vedolizumab |
| D000069549 | Ustekinumab |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D061067 | Antibodies, Monoclonal, Humanized |
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