Nicholas A. Kennedy
A5047522708- Inflammatory Bowel Disease
- Microscopic Colitis
- Immunodeficiency and Autoimmune Disorders
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Eosinophilic Esophagitis
- Acute Lymphoblastic Leukemia research
- Helicobacter pylori-related gastroenterology studies
- Biosimilars and Bioanalytical Methods
- Chronic Lymphocytic Leukemia Research
- COVID-19 and healthcare impacts
- Health Systems, Economic Evaluations, Quality of Life
- Gut microbiota and health
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Screening and Detection
- Autoimmune and Inflammatory Disorders Research
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Iron Metabolism and Disorders
- Celiac Disease Research and Management
- Mycobacterium research and diagnosis
- Diverticular Disease and Complications
- Systemic Lupus Erythematosus Research
- Diagnosis and treatment of tuberculosis
- Tuberculosis Research and Epidemiology
University of Exeter
2016-2025
Royal Devon & Exeter NHS Foundation Trust
2016-2025
West Virginia University
2024
Royal Devon and Exeter Hospital
2017-2023
Phillips Exeter Academy
2020-2023
Edinburgh Cancer Research
2023
University Teaching Hospital
2023
Australia and New Zealand Banking Group
2023
University of Edinburgh
2013-2022
Institute of Genetics and Cancer
2012-2022
Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies identified 163 susceptibility loci for disease, mostly shared between colitis. We undertook largest genotype association study, to date, in widely used clinical subphenotypes with goal further understanding biological relations diseases.
Background & AimsAnti–tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce formation of anti-drug antibodies. The ability to identify patients at increased risk development antibodies would facilitate selection therapy and use preventative strategies.MethodsWe performed a genome-wide association study variants associated with time in discovery cohort 1240 biologic-naïve Crohn's disease...
Determining bacterial community structure in fecal samples through DNA sequencing is an important facet of intestinal health research. The impact different commercially available extraction kits upon structures has received relatively little attention. aim this study was to analyze communities volunteer and inflammatory bowel disease (IBD) patient extracted using widely used established gastrointestinal research laboratories.Fecal from two healthy volunteers (H3 H4) relapsing IBD patients...
Objective Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more the population. We investigated whether patients with inflammatory bowel disease treated infliximab have attenuated serological responses to single vaccine. Design Antibody and seroconversion rates in infliximab-treated (n=865) were compared cohort vedolizumab (n=428), gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike...
The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be to protect our patients clinical services they rely on. This a novel coronavirus; much unknown as how it will affect people with IBD. We also lack information about impact different immunosuppressive medications....
Abstract Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) 5 regions (DMRs), which study detail using whole genome bisulphite sequencing. We replicate the top DMP ( RPS6KA2 ) DMRs VMP1, ITGB2 TXK an independent cohort. Using paired genetic epigenetic...
The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into role genetics in prognosis. We identify noncoding polymorphism FOXO3A (rs12212067: T > G) at which minor (G) allele, despite not being associated with susceptibility, milder...
Abstract GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that perturbed these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and 23,650 cis -eQTL. We show determined ∼9720 modules, which ∼3000 operate in multiple tissues ∼970 on genes. modules drive association 63 200 loci, enriched multigenic...
Abstract Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS independent cohorts. conducted genome-wide association study 53,400 433,201 controls replicated significant associations in 23andMe panel (205,252 1,384,055 controls). Our confirmed six genetic loci IBS. Implicated...
Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses SARS-CoV-2 infections.Antibody in participants treated infliximab were compared a reference cohort vedolizumab, gut-selective anti-integrin α4β7 monoclonal antibody that is not associated impaired...
IMPORTANCEUse of thiopurines may be limited by myelosuppression.TPMT pharmacogenetic testing identifies only 25% at-risk patients European ancestry.Among East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM).OBJECTIVE To identify genetic TIM among ancestry inflammatory bowel disease (IBD). DESIGN, SETTING, AND PARTICIPANTSCase-control study 491 affected and 679 thiopurine-tolerant unaffected who were recruited from 89 international sites between...
BackgroundThe effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought determine whether COVID-19 vaccine-induced antibody were altered in patients with IBD commonly used immunosuppressive drugs.MethodsIn this multicentre, prospective, case-control study (VIP), recruited adults treated one of six different treatment regimens (thiopurines, infliximab, a thiopurine plus ustekinumab, vedolizumab,...
BackgroundManagement strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing randomised either top-down (ie, early combined immunosuppression infliximab immunomodulator) or accelerated step-up (conventional) treatment strategies.MethodsPROFILE (PRedicting Outcomes For disease using moLecular biomarker) was multicentre, open-label, biomarker-stratified,...
The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities vary factors such as ethnicity. We aimed to assess the adults those therapies.
Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses breakthrough infections in patients with inflammatory bowel disease, who are treated either anti-TNF antibody, infliximab, or vedolizumab targeting a gut-specific anti-integrin that does not systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations...
BackgroundWe sought to report the effectiveness of infliximab and adalimumab over first 3 years treatment define factors that predict anti-TNF failure strategies prevent or mitigate loss response.MethodsPersonalised Anti-TNF therapy in Crohn's disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting rates anti-TNF-naive patients with active luminal aged 6 older. At end year, sites were invited enrol participants still receiving drug into 2-year...
Escherichia coli cells carrying the F sex factor are poor recipients in conjugation. This phenomenon is called surface exclusion. Two cistrons, traS and traT, independently responsible for part of whole mechanism. The gene product reduces DNA transfer within stable mating aggregates. traT product, pTraT, results a greatly reduced ability to form aggregates, thus also leads cell population. pTraT 25,000-dalton protein incorporated into envelope outer membrane. It found 29,000-84,000 copies...