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Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.
Nat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
View Article and Find Full Text PDFThe modulating effect of circulating carbohydrate antigen 125 on ST2 and long-term recurrent morbidity burden.
Sci Rep
January 2025
CIBER Cardiovascular, Madrid, Spain.
Soluble ST2 (sST2) is released in response to vascular congestion, inflammation, and pro-fibrotic stimuli. In heart failure (HF), elevated levels of sST2 are associated with a higher risk of adverse clinical outcomes. Emerging evidence suggests that carbohydrate antigen 125 (CA125) may act as a ligand that modulates the inflammatory response.
View Article and Find Full Text PDFStudy protocol for Adaptive ChemoTherapy for Ovarian cancer (ACTOv): a multicentre phase II randomised controlled trial to evaluate the efficacy of adaptive therapy (AT) with carboplatin, based on changes in CA125, in patients with relapsed platinum-sensitive high-grade serous or high-grade endometrioid ovarian cancer.
BMJ Open
December 2024
University College London Hospitals NHS Foundation Trust, London, UK
Introduction: Adaptive ChemoTherapy for Ovarian cancer (ACTOv) is a phase II, multicentre, randomised controlled trial, evaluating an adaptive therapy (AT) regimen with carboplatin in women with relapsed, platinum-sensitive high-grade serous or high-grade endometrioid cancer of the ovary, fallopian tube and peritoneum whose disease has progressed at least 6 months after day 1 of the last cycle of platinum-based chemotherapy. AT is a novel, evolutionarily informed approach to cancer treatment, which aims to exploit intratumoral competition between drug-sensitive and drug-resistant tumour subpopulations by modulating drug dose according to a patient's own response to the last round of treatment. ACTOv is the first clinical trial of AT in this disease setting.
View Article and Find Full Text PDFIdentification of a circulating carbohydrate antigen as a highly specific and sensitive target for schistosomiasis serology.
J Clin Microbiol
January 2025
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
Unlabelled: The World Health Organization (WHO) 2030 roadmap for schistosomiasis calls for development of highly sensitive and specific diagnostic tools to continue and sustain progress towards elimination. Serological assays are excellent for sensitive detection of primary schistosome infections and for schistosomiasis surveillance in near- and post-elimination settings. To develop accurate assay formats, it is necessary to identify defined antibody targets with low cross-reactivity and potential for standardized production.
View Article and Find Full Text PDFThe Role of Vimentin Peptide Citrullination in the Structure and Dynamics of HLA-DRB1 Rheumatoid Arthritis Risk-Associated Alleles.
Int J Mol Sci
December 2024
Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Citrullination, a post-translational modification (PTM), plays a critical role in rheumatoid arthritis (RA) by triggering immune responses to citrullinated self-antigens. Some HLA-DRB1 genes encode molecules with the shared epitope (QKRAA/QRRAA) sequence in the peptide-binding groove which preferentially presents citrulline-modified peptides, like vimentin, that intensifies the immune response in RA. In this study, we used computational approaches to evaluate intermolecular interactions between vimentin peptide-ligands (with/without PTM) and HLA-DRB1 alleles associated with a significantly increased risk for RA development.
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