Advances in Imaging Specific Mediators of Inflammatory Bowel Disease

Dmochowska, Nicole; Wardill, Hannah R.; Hughes, Patrick A.

doi:10.3390/ijms19092471

Cited by 39 publications

(47 citation statements)

References 61 publications

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“…ImmunoPET directed against immune cells or mediators has demonstrated efficacy for detecting colonic inflammation in pre-clinical models 16 , 19 – 21 . We recently demonstrated that targeting inflammation induced immune mediators such as IL-1β results in a substantially more localized bio-distribution than targeting immune cells, presumably as while immune cells migrate to inflamed sites they are also widely distributed throughout the body 20 .…”

Section: Discussionmentioning

confidence: 99%

“…Diagnostic tools are ideally sensitive, quantitative and selective for their pathology, non-invasive to the patient, provide information rapidly and do not influence the disease process 5 , 16 . Stricture can be detected by endoscopy, however endoscopy is limited to imaging only the mucosal surface and not the deeper layers of the colon wall where fibrosis develops 17 .…”

Section: Introductionmentioning

confidence: 99%

“…Stricture can be detected by endoscopy, however endoscopy is limited to imaging only the mucosal surface and not the deeper layers of the colon wall where fibrosis develops 17 . Molecular imaging approaches including positron emission tomography (PET) have superior sensitivity and provide quantitative information 16 , 18 . ImmunoPET combines the superior target selectivity provided by antibodies with the sensitivity of PET and we, amongst others, have previously demonstrated that immunoPET strategies effectively detect intestinal inflammation 16 , 19 – 21 .…”

Section: Introductionmentioning

confidence: 99%

“…Molecular imaging approaches including positron emission tomography (PET) have superior sensitivity and provide quantitative information 16 , 18 . ImmunoPET combines the superior target selectivity provided by antibodies with the sensitivity of PET and we, amongst others, have previously demonstrated that immunoPET strategies effectively detect intestinal inflammation 16 , 19 – 21 . However, the use of intact antibodies as molecular imaging probes is challenging as their relatively high molecular weight results in long half-lives, potentially translating into increased patient exposure to ionizing radiation, and it may also impede the penetration of fibrotic tissue 22 .…”

Section: Introductionmentioning

confidence: 99%

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89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis

Dmochowska

Tieu

Keller

et al. 2020

Sci Rep

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Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab′)2 antibody fragments targeting MMPs detects colitis induced colonic fibrosis. Mice were administered 2% dextran sulfate sodium treated water for 1 cycle (inflamed) or 3 cycles (fibrotic), or were untreated (control). Colonic and kidney collagen, innate cytokine, MMPs and fecal MPO concentrations were analyzed by multiplex/ELISA. α-pro-MMP-9 F(ab′)2 fragments were engineered and conjugated to 89Zr for PET imaging, ex-vivo Cherenkov analysis and bio-distribution. Colonic innate cytokine concentrations and fecal myeloperoxidase were increased in inflamed mice but not fibrotic mice, while collagen concentrations were increased in fibrotic mice. MMPs were increased in inflamed mice, but only pro-MMP-9 remained increased in fibrotic mice. 89Zr-pro-MMP-9 F(ab′)2 uptake was increased in the intestine but also in the kidney of fibrotic mice, where collagen and pro-MMP-9 concentrations were increased. 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal fibrosis and associated kidney fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis

Dmochowska

Tieu

Keller

et al. 2020

Sci Rep

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“…In ammatory response during IBD is caused by induced Th1/Th17 effector cells and impaired regulatory cells including regulatory T cells (Treg), B cells (Breg), M2 macrophages, dendritic cells (CD103 + DCs) and innate lymphoid cells (ILCs) [6,16,17]. Regulatory cell-mediated immune tolerance to foreign antigens and autologous proteins in the colon is important to inhibit IBD [18]. Tregs play a key role in immunological tolerance through secretion of inhibitory cytokines, and Tregs could disrupt metabolic processes in T effector lymphocytes (Teffs), induce apoptosis of Teffs, trigger cytotoxic activity against Teffs, neutralize DC function, and produce amphiregulin to repair tissue [19].…”

Section: Introductionmentioning

confidence: 99%

Enterobacter Ludwigii Protects Experimental Colitis Through CD103+DC and Treg Cells

Li¹,

Sun²,

Kobayashi³

et al. 2020

Preprint

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Background: Intestinal bacteria are closely related with inflammatory bowel disease (IBD), and regulatory cell-mediated immune tolerance is important to inhibit IBD. Commensal intestinal bacteria play key roles in regulating immune tolerance cell, however, bacterial strains directly involved in this regulation remain to be identified.Results: In the present study, metronidazole, among nine antibiotics, was found to have the best effect on protecting mice against DSS-induced colitis. Enterobacter ludwigi, abundant in mouse feces after metronidazole treatment, was identified to decrease mice susceptibility to DSS-induced colitis with or without the presence of complex intestinal bacteria. E. ludwigii gavage increased CD103+DCs and Foxp3+Treg cells in intestinal microenvironment, and effects of E. ludwigii on diminishing colitis were lost in DC or Treg depletion mice. CD103+DCs isolated from E. ludwigii-treated mice showed enhanced ability to promote the Treg differentiation from naive T cells. DCs, directly stimulated by live E. ludwigii strain or its culture supernatant, had increased immune tolerance ability for Treg differentiation in vitro. Conclusions: Overall, our findings identify a facultative anaerobe bacterial strain E. ludwigii, which directly enhances CD103+DC and Treg-mediated immune tolerance, resulting in protecting mice against DSS-induced colitis.

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Effect of a gamified mobile‐based self‐management application on disease activity index, quality of life, and mental health in adults with inflammatory bowel disease: A protocol of a randomized controlled trial study

Norouzkhani,

Faramarzi,

Bahari

et al. 2024

Health Science Reports

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Background and AimsInflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal tract disease subdivided into Crohn's disease (CD) and ulcerative colitis (UC). There is currently no cure for IBD, and individuals with IBD frequently experience a lower health‐related quality of life (HRQOL) than the general population. Gamification has become an increasingly popular topic in recent years. Adapting game design concepts to nongaming contexts represents a novel and potential approach to changing user engagement. This study will be conducted with the aim of evaluating the effect of a gamified mobile‐based self‐management application on disease activity index, quality of life, and mental health in adults with IBD.MethodsA multicenter, parallel, two‐arm, exploratory randomized controlled trial with a 6‐month follow‐up per patient will be designed to compare the impact of the gamified mobile‐based tele‐management system on primary and secondary health outcomes and outpatient visits in 210 patients with all types of IBD which are divided equally into a control group with standard care and an intervention group which will use the developed mobile application named MY IBD BUDDY. All patients will attend study visits at baseline, 12 and 24 weeks, and routine IBD clinic visits or telephone consultations based on randomization group assignment. Disease activity or disease activity index, mental health (anxiety and depression) symptoms, quality of life, self‐efficacy, and IBD‐specific knowledge will be measured at baseline with two follow‐ups at 12 and 24 weeks.ConclusionsIn sum, the outcomes of our trial will demonstrate the impact of the gamified mobile‐based self‐management system on disease activity, quality of life, and anxiety and depression by means of interactive care and patient empowerment.Trial RegistrationIRCT: IRCT20200613047757N1. Registered November 16, 2021. Prospectively registered and visible at OSF (https://doi.org/10.17605/OSF.IO/AWFY9).

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Advances in Imaging Specific Mediators of Inflammatory Bowel Disease

Cited by 39 publications

References 61 publications

89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis

89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis

Enterobacter Ludwigii Protects Experimental Colitis Through CD103+DC and Treg Cells

Effect of a gamified mobile‐based self‐management application on disease activity index, quality of life, and mental health in adults with inflammatory bowel disease: A protocol of a randomized controlled trial study

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