Charlotte Höög

Capsule Retentions and Incomplete Capsule Endoscopy Examinations: An Analysis of 2300 Examinations

Aim. To evaluate capsule endoscopy in terms of incomplete examinations and capsule retentions and to find risk factors for these events. Material and Methods. This retrospective and consecutive study includes data from 2300 capsule enteroscopy examinations, performed at four different hospitals in Stockholm, Sweden from 2003 to 2009. Results. The frequency of incomplete examinations was 20%. Older age, male gender, suspected, and known Crohns disease were risk factors for an incomplete examination. The PillCam capsule had the highest rate of completed examinations. Capsule retention occurred in 1.3% (n = 31). Risk factors for capsule retention were known Crohns disease and suspected tumor. Complications of capsule retention were acute obstructive symptoms in six patients and one death related to complications after acute surgical capsule retrieval. Conclusion: Capsule endoscopy is considered a safe procedure, although obstructive symptoms and serious complications due to capsule retention can be found in a large series of patients.

CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

SUMMARY Tissue‐resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced interferon‐&ggr;, whereas CD8+CD49a− Trm cells produced interleukin‐17 (IL‐17). In addition, CD8+CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL‐15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8+CD49a+ Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8+CD49a– Trm cells from psoriasis lesions predominantly generated IL‐17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8+ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases. Graphical Abstract Figure. No Caption available. HighlightsCD49a expression marks CD8+ Trm cells poised for IFN‐&ggr; production in human skinIL‐15 drives potent cytotoxic capacity in CD49a+ Trm cellsIL‐17 is preferentially produced by CD49a− CD8+ Trm cells in the skinCD49a+ versus CD49‐ Trm cell functional dichotomy is preserved in vitiligo and psoriasis &NA; Tissue‐resident memory T (Trm) cells provide localized adaptive immunity in peripheral tissues. Cheuk et al. identify cytotoxic CD49a+CD8+ Trm cells and IL‐17‐producing CD49a−CD8+ Trm cells in healthy human skin. The functional dichotomy of pathogenic Trm cells based on CD49a expression is preserved in focal skin diseases vitiligo and psoriasis.

Capsule endoscopic findings correlate with fecal calprotectin and C-reactive protein in patients with suspected small-bowel Crohn’s disease

Abstract Objective. Capsule endoscopy (CE) is a sensitive method for detecting inflammatory lesions in the small bowel. Such lesions may be due to Crohn’s disease but also to other causes and a histological diagnosis may be difficult to achieve in the small bowel. The aim of the study was to find a possible correlation between capsule endoscopic findings, biochemical parameters, and symptoms in patients with suspected or known small-bowel Crohn´s disease. Materials and methods. Thirty patients with inflammatory lesions in the small bowel diagnosed by CE were included. CE findings of inflammation were graded using the Lewis score. C-reactive protein (CRP) and fecal calprotectin were used as biochemical parameters. Symptoms were graded using the Harvey–Bradshaw index. The patients were followed up after 9 months with a second CE, CRP, fecal calprotectin, and Harvey–Bradshaw index. Results. There was a significant persistent correlation between endoscopic inflammation and fecal calprotectin (p = 0.003 at inclusion and p < 0.001 at follow-up). CRP was correlated to endoscopic inflammation at inclusion (p = 0.006), but not at follow-up. Symptoms were not correlated with endoscopic inflammation. Conclusion. Inflammatory lesions in the small bowel diagnosed by CE in patients with suspected Crohn´s disease are correlated to fecal calprotectin and CRP, but not to symptoms.

Findings in patients with chronic intestinal dysmotility investigated by capsule endoscopy

BackgroundCapsule endoscopy (CE) is a unique tool to visualize the mucosa of the small intestine. Chronic intestinal dysmotility (CID) is a group of rare disorders of gastrointestinal motility that often are complicated by bacterial overgrowth. The aim of this study was to determine the prevalence of small bowel mucosal abnormalities in patients with CID. We also studied the usefulness of CE in the diagnosis of intestinal dysmotility.MethodsWe conducted a prospective study using CE in 18 patients; six with myopathic, 11 with neuropathic and one with indeterminate CID. A control group was used for comparison of small bowel transit.ResultsMucosal breaks (erosions and ulcerations) were found in 16/18 (89%) patients. The capsule reached the caecum in 11/18 (61%) patients with a median transit time of 346 minutes. In the control group the capsule reached the caecum in 29/36 (81%) cases with a median transit time of 241 minutes. The difference in transit time was not significant (p = 0.061) in this material. The capsule was retained in the stomach in 3/18 patients. None of the patients developed symptoms or signs of mechanical obstruction.ConclusionA high frequency of mucosal breaks and signs of motility disturbances were seen in CID patients. CE is feasible for the examination of small bowel mucosa in patients with CID. The relevance of observed mucosal abnormalities in CID remains uncertain.

Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells

&NA; Figure. No caption available. Background: Vitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL‐23–driven tissue‐resident group 3 innate lymphoid cells (ILC3s) play essential roles in intestinal immunity, and targeting IL‐23/12 is a promising approach in IBD therapy. Objective: We set out to define the role of 1&agr;,25‐dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3s to IL‐23 plus IL‐1&bgr; stimulation. Methods: Transcriptomes of sorted tonsillar ILC3s were assessed by using microarray analysis. ILC3 cytokine production, proliferation, and differentiation were determined by means of flow cytometry, ELISA, and multiplex immunoassay. Intestinal cell suspensions and ILC3s sorted from gut biopsy specimens of patients with IBD were also analyzed along with plasma 25‐hydroxy vitamin D3 (25D) detection. Results: ILC3s stimulated with IL‐23 plus IL‐1&bgr; upregulated the vitamin D receptor and responded to 1,25D with downregulation of the IL‐23 receptor pathway. Consequently, 1,25D suppressed IL‐22, IL‐17F, and GM‐CSF production from tonsillar and gut ILC3s. In parallel, 1,25D upregulated genes linked to the IL‐1&bgr; signaling pathway, as well as the IL‐1&bgr;–inducible cytokines IL‐6, IL‐8, and macrophage inflammatory protein 1&agr;/&bgr;. The 1,25D‐triggered skewing in ILC3 function was not accompanied or caused by changes in viability, proliferation, or phenotype. Finally, we confirmed low 25D plasma levels in patients with IBD with active inflammation. Conclusion: In light of the beneficial targeting of IL‐23/12 in patients with IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL‐23 receptor pathway, providing a novel mechanism for how ILC3s could be manipulated to regulate intestinal inflammation.

Bleeding from gastrointestinal angioectasias is not related to bleeding disorders - a case control study

BackgroundAngioectasias in the gastrointestinal tract can be found in up to 3% of the population. They are typically asymptomatic but may sometimes result in severe bleeding. The reasons for why some patients bleed from their angioectasias are not fully understood but it has been reported that it may be explained by an acquired von Willebrand syndrome (AVWS). This condition has similar laboratory findings to congenital von Willebrand disease with selective loss of large von Willebrand multimers. The aim of this study was to find out if AVWS or any other bleeding disorder was more common in patients with bleeding from angioectasias than in a control group.MethodsWe compared bleeding tests and coagulation parameters, including von Willebrand multimers, from a group of 23 patients with anemia caused by bleeding from angioectasias, with the results from a control group lacking angioectasias.ResultsNo significant differences between the two groups were found in coagulation parameters, bleeding time or von Willebrand multimer levels.ConclusionThese results do not support a need for routine bleeding tests in cases of bleeding from angioectasias and do not show an overall increased risk of AVWS among these patients.

Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo

A common helper-like innate lymphoid precursor (CHILP) restricted to the innate lymphoid cells (ILC) lineage has been recently characterized. While specific requirements of transcription factors for CHILPs development has been partially described, their ability to sense cytokines and react to peripheral inflammation remains unaddressed. Here, we found that systemic increase in Flt3L levels correlated with the expansion of Lineage (Lin)negα4β7+ precursors in the adult murine bone marrow. Expanded Linnegα4β7+ precursors were bona fide CHILPs as seen by their ability to differentiate into all helper ILCs subsets but cNK in vivo. Interestingly, Flt3L-expanded CHILPs transferred into lymphopenic mice preferentially reconstituted the small intestine. While we did not observe changes in serum Flt3L during DSS-induced colitis in mice or plasma from inflammatory bowel disease (IBD) patients, elevated Flt3L levels were detected in acute malaria patients. Interestingly, while CHILP numbers were stable during the course of DSS-induced colitis, they expanded following increased serum Flt3L levels in malaria-infected mice, hence suggesting a role of the Flt3L-ILC axis in malaria. Collectively, our results indicate that Flt3L expands CHILPs in the bone marrow, which might be associated with specific inflammatory conditions.

Systemic Chemokine Levels with “Gut-Specific” Vedolizumab in Patients with Inflammatory Bowel Disease—A Pilot Study

Vedolizumab, a gut-specific biological treatment for inflammatory bowel disease (IBD), is an antibody that binds to the α4β7 integrin and blocks T-cell migration into intestinal mucosa. We aimed to investigate chemokine levels in serum of IBD-patients treated with vedolizumab. In this pilot study, we included 11 IBD patients (8 Crohn’s disease, 3 ulcerative colitis) previously non-respondent to anti-tumor necrosis factor (TNF)-agents. Patients received vedolizumab at week 0, 2 and 6 and were evaluated for clinical efficacy at week 10. Clinical characteristics and routine laboratory parameters were obtained and patients were classified as responders or non-responders. Expression of 21 chemokines in serum was measured using Proximity Extension Assay and related to clinical outcome. At week 10, 6 out of 11 patients had clinically responded. Overall expression of CCL13 increased after treatment. In non-responders, expression of CCL13 and CXCL8 increased after treatment, and CCL20 and CXCL1 expressions were higher compared to responders. In responders, CCL28 decreased after treatment. C-reactive protein (CRP) correlated negatively with 6 chemokines before therapy, but not after therapy. Systemic CCL13 expression increases in IBD-patients after vedolizumab therapy and several chemokine levels differ between responders and non-responders. An increased CCL13-level when starting vedolizumab treatment, might indicate potential prognostic value of measuring chemokine levels when starting therapy with vedolizumab. This study provides new information on modulation of systemic chemokine levels after vedolizumab treatment.