A5041570096- Drug-Induced Adverse Reactions
- Asthma and respiratory diseases
- Drug-Induced Hepatotoxicity and Protection
- Mast cells and histamine
- Immune Cell Function and Interaction
- Urticaria and Related Conditions
- Pharmacogenetics and Drug Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
- Autoimmune Bullous Skin Diseases
- Contact Dermatitis and Allergies
- Pneumocystis jirovecii pneumonia detection and treatment
- T-cell and B-cell Immunology
- Hepatitis C virus research
- Biosimilars and Bioanalytical Methods
- Cystic Fibrosis Research Advances
- Immunodeficiency and Autoimmune Disorders
- Allergic Rhinitis and Sensitization
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Blood disorders and treatments
- Tryptophan and brain disorders
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Phenothiazines and Benzothiazines Synthesis and Activities
University of Liverpool
2016-2025
Leibniz-Institute for New Materials
2023
Medical Research Council
2010-2020
Drug Safety Research Unit
2015-2016
Liverpool Hospital
2015
Cancer Research UK
2014
University of Toronto
2000-2013
St James's University Hospital
2012
St. James's Hospital
2012
University of Oxford
2011
The role of the adaptive immune system in adverse drug reactions that target liver has not been defined. For flucloxacillin, a delay reaction onset and identification human leukocyte antigen (HLA)-B*57:01 as susceptibility factor are indicative an pathogenesis. Thus, we characterize flucloxacillin-responsive CD4+ CD8+ T cells from patients with injury show naive CD45RA+CD8+ volunteers expressing HLA-B*57:01 activated flucloxacillin when dendritic present antigen. T-cell clones CCR4 CCR9...
Abstract Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with from those cross-reactive immunity to other coronaviruses. Here we show a range assays that differentially capture immune function characterise responses. Strong ex vivo ELISpot and proliferation multiple antigens (including M, NP ORF3) are found in 168 PCR-confirmed volunteers, but rare 119 uninfected volunteers. Highly exposed seronegative healthcare workers recent...
Administration of carbamazepine (CBZ) causes hypersensitivity reactions clinically characterized by skin involvement, eosinophilia, and systemic symptoms. These have an immune etiology; however, the role T cells is not well defined. The aim this study was to characterize specificity, phenotype, cytokine profile CBZ-specific derived from hypersensitive individuals. Proliferation blood lymphocytes measured using lymphocyte transformation test. cell clones were generated serial dilution in...
Abstract The recognition of the antibiotic sulfamethoxazole (SMX) by T cells is usually explained with hapten-carrier model. However, recent investigations have revealed a MHC-restricted but processing- and metabolism-independent pathway drug presentation. This suggested labile, low-affinity binding SMX to MHC-peptide complexes on APC. To study role covalent vs noncovalent presentation in allergy, we analyzed proliferative response PBMC cell clones from patients allergy its reactive...
Drug-induced liver injury (DILI) frequently has a delayed onset with several human leukocyte antigen (HLA) genotypes affecting susceptibility, indicating potential role for the adaptive immune system in disease. The aim of this study was to investigate whether drug-responsive T lymphocytes are detectable patients who developed DILI combination, antimicrobial amoxicillin-clavulanate. Lymphocytes from 6 7 were found proliferate and/or secrete interferon-gamma (IFN-γ) when cultured amoxicillin...
Sulphamethoxazole has been associated with the occurrence of hypersensitivity reactions. There is controversy as to whether immune response metabolism‐dependent or ‐independent. We have therefore investigated site antigen formation and nature drug signal presented system in vivo . Male Wistar rats were dosed sulphamethoxazole, sulphamethoxazole hydroxylamine nitroso sulphamethoxazole. Antigen on cell surfaces was determined by flow cytometry using a specific anti‐sulphamethoxazole antibody....
Treatment with sulfamethoxazole (SMX) can lead to hypersensitivity reactions. T cells from hypersensitive patients recognize either the parent drug and/or reactive nitroso (SMX-NO) metabolite. In this study, using a novel in vitro rat splenocyte assay, we have investigated toxicological and immunological consequences of cell surface haptenation by SMX-NO. SMX-NO was found be unstable solution; spontaneous transformation yielded appreciable amounts SMX-hydroxylamine, nitro-SMX, previously...
Abstract Different signals in addition to the antigenic signal are required initiate an immunological reaction. In context of sulfamethoxazole allergy, Ag is thought be derived from its toxic nitroso metabolite, but little known about costimulatory signals, including those associated with dendritic cell maturation. this study, we demonstrate increased CD40 expression, not CD80, CD83, or CD86, surfaces exposed (250–500 μM) and protein-reactive metabolite (1–10 μM). Increased expression was...
A mechanistic understanding of the relationship between chemistry drug Ag formation and immune function is lacking. Thus, mass spectrometric methods were employed to detect fully characterize circulating Ags derived from piperacillin in patients undergoing therapy nature drug-derived epitopes on protein that can as an stimulate T cells. Albumin modification with vitro resulted two distinct haptens, one formed directly a second which dioxopiperazine ring had undergone hydrolysis. Modification...