- Inflammatory Bowel Disease
- Microscopic Colitis
- Liver Diseases and Immunity
- Helicobacter pylori-related gastroenterology studies
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Celiac Disease Research and Management
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Biosimilars and Bioanalytical Methods
- Gastric Cancer Management and Outcomes
- Acute Lymphoblastic Leukemia research
- Digestive system and related health
- Tuberculosis Research and Epidemiology
- Diagnosis and treatment of tuberculosis
- Colorectal Cancer Surgical Treatments
- Pregnancy and Medication Impact
- Eosinophilic Esophagitis
- Whipple's Disease and Interleukins
- Colorectal Cancer Screening and Detection
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- T-cell and B-cell Immunology
- S100 Proteins and Annexins
King's College Hospital
2014-2025
King's College Hospital NHS Foundation Trust
2016-2025
King's College London
2014-2025
Guy's and St Thomas' NHS Foundation Trust
2013-2023
Kings Health Partners
2016-2022
St Thomas' Hospital
2020
Guy's Hospital
2017
East Surrey Hospital
2014-2016
Surrey and Sussex Healthcare NHS Trust
2014-2016
University Gastroenterology
2016
The function of interleukin-22 (IL-22) in intestinal barrier homeostasis remains controversial. Here, we map the transcriptional landscape regulated by IL-22 human colonic epithelial organoids and evaluate biological, functional clinical significance mediated pathways ulcerative colitis (UC). We show that pro-inflammatory are involved microbial recognition, cancer immune cell chemotaxis; most prominently those involving CXCR2
Regulatory T cells (Tregs) play a pivotal role in maintaining immunological tolerance, but they can also detrimental by preventing antitumor responses. Here, we characterized helper (Th)-like Treg subsets to further delineate their biological function and tissue distribution, focusing on possible contribution disease states. RNA sequencing functional assays revealed that Th2-like Tregs displayed higher viability autocrine interleukin-2 (IL-2)-mediated activation than other subsets. were...
Abstract The induction of human CD4 + Th1 cells requires autocrine stimulation the complement receptor CD46 in direct crosstalk with a T cell-intrinsic NLRP3 inflammasome. However, it is unclear whether cytotoxic CD8 cell (CTL) responses also rely on an intrinsic complement-inflammasome axis. Here we show, using CTLs from patients deficiency or constitutively-active NLRP3, that delivers co-stimulatory signals for optimal CTL activity by augmenting nutrient-influx and fatty acid synthesis....
Objective. Assessment of faecal calprotectin (fCal) test performance in primary care within an irritable bowel syndrome (IBS) diagnostic pathway. Methods. Study based on consecutively collected fCal data from 962 patients, aged 18–45, presenting to their general practitioner (GP) with persistent gastrointestinal symptoms. Results. Six hundred and eighty six (71%) patients had a negative (<50 μg/g) 276 (29%) positive fCal. 28% (77/276) the testing 3% (17/686) those organic diagnosis. At 50...
Abstract Background Glycoprotein 2 (GP2) was discovered as the major autoantigen of Crohn’s disease (CD)-specific pancreatic autoantibodies (PAB). We investigated anti-GP2 IgA and IgG antibodies novel serological parameters in CD assessed their association with distinct phenotypes. Methods Anti-GP2 anti-Saccharomyces cerevisiae (ASCA) were detected by ELISA employing recombinant human GP2 phosphopeptidomannan, respectively PAB indirect immunofluorescence (IIF) 271 sera, 169 102 ulcerative...
To gain an understanding of the efficacy vedolizumab in a 'real-world' setting.Retrospective cohort study using prospectively maintained clinical records.Two UK tertiary inflammatory bowel disease (IBD) centres.Patients with IBD commenced on at Guy's & St Thomas' and King's College Hospitals during November 2014-November 2015.Vedolizumab, monoclonal antibody to α-4 β-7 integrins that selectively inhibit leucocyte migration into gut.Clinical activity was assessed baseline, weeks 14 30...
Background. Severe acute pancreatitis (SAP) is associated with serious morbidity and mortality. Our objective was to describe the case mix, management, outcome of patients SAP receiving modern critical care in Intensive Care Unit (ICU). Methods. Retrospective analysis admitted ICU a single tertiary centre UK between January 2005 December 2010. Results. Fifty were (62% male, mean age 51.7 (SD 14.8)). The most common aetiologies alcohol (40%) gallstones (30%). On admission ICU, median Acute...
Summary Background Low‐quality evidence suggests that pre‐operative exclusive enteral nutrition (E/EN) can improve postoperative outcomes in patients with Crohn's disease (CD). It is not standard practice most centres. Aims To test the hypothesis EN undergoing ileal/ileocolonic surgery for CD associated improved outcome. Methods We performed a single centre retrospective observational study comparing surgical receiving (≥600 kcal/day ≥2 weeks) those who received no nutritional optimisation....
Interactions between the epithelium and immune system are critical in pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped transcriptional landscape human colonic epithelial organoids response to different cytokines responsible for mediating canonical mucosal responses. By profiling transcriptome treated with interferon gamma, interleukin-13, -17A, tumor necrosis factor alpha next-generation sequencing, unveil shared distinct regulation patterns function by cytokines....
Abstract Background Inflammatory Bowel Disease (IBD) with Liver Transplantation (LT) presents a complex dilemma between disease control versus immunosuppression. The association of IBD and primary sclerosing cholangitis (PSC), alongside increasing metabolic dysfunction-associated fatty liver (MAFLD) in the population, is likely to increase number requiring LT. (1) While immunosuppression therapy post-transplant standardised, proliferation advanced therapies for have unknown efficacy safety...
Abstract Background Tofacitinib (TOF) is an effective treatment for ulcerative colitis (UC). A relationship between dose and both response side-effect profile recognised JAK inhibitors. Dose reduction from 10mg bd to 5mg therefore associated with improved safety but also a risk of relapse. The BRITE study aimed identify clinical predictors biomarkers relapse in cohort patients stable UC undergoing TOF reduction. Methods Steroid-free responding at least 8 weeks were followed time or one year....
Abstract Background Dye chromoendoscopy (DCE) with targeted biopsies has traditionally been considered the gold standard for optimal detection of dysplasia in context inflammatory bowel disease (IBD) surveillance. Randomised trials have challenged this both virtual (VCE) and high-definition white light endoscopy (WLE) appearing to comparable yield. This multicentre UK study aims test hypothesis that neoplasia rate (NDR) IBD surveillance as part routine clinical care is not affected by...
Why zymogen glycoprotein 2 (GP2), the Crohn’s disease (CD)-specific pancreatic autoantigen, is major target of humoral autoimmunity in inflammatory bowel diseases (IBD) uknown. Recent evidence demonstrates that GP2 also present on apical surface microfold (M) intestinal cells. As colon lacks GP2-rich M cells, we assumed patients with colonic CD are seronegative for anti-GP2. Anti-GP2 antibodies were tested 225 CDs, including 45 location (L2), terminal ileum (L1) and 135 ileocolonic...
Low-dose azathioprine with allopurinol (LDAA) has been proposed as a potent therapy in inflammatory bowel disease (IBD) the benefit of overcoming side effects regularly associated thiopurine monotherapy and poor responses. Concerns regarding safety remain, while layer complexity added by trend toward treatment directed red cell thioguanine nucleotide (TGN) profiling. We report on clinical efficacy LDAA use IBD undirected metabolite profiling.Observational study practice from single center....
Thioguanine (TG) is a treatment for inflammatory bowel disease, but association with nodular regenerative hyperplasia has restricted its use. We conjectured that splitting therapeutic daily dose of TG would be efficacious and should avoid liver toxicity.We report on 62 patients severe disease not responding to prednisolone, conventional thiopurines, biologics, or calcineurin inhibitors. Patients were prescribed oral split-daily individual doses >0.3 mg/kg. Data concomitant medication,...
Pancreatic autoantibodies (PAB) targeting GP2 and CUZD1 are Crohn's disease (CrD)-markers. The clinical significance of anti-GP2 antibodies has been assessed, but that anti-CUZD1 remains elusive. aim the study was to assess utility anti-CUZD1/anti-GP2 by novel cell-based indirect immunofluorescence (IIF) assays in CrD.A total 212 CrD 249 UC patients followed up at a London IBD centre were investigated simultaneously detect PABs, IIF using primate pancreatic tissue, HEK293 over-expressing or...