ORCID Profile
0000-0001-5977-6602
Current Organisation
University of Oxford
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Publisher: Cold Spring Harbor Laboratory
Date: 21-10-2020
DOI: 10.1101/2020.10.19.20214395
Abstract: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to COVID-19 infection, progression to symptoms, likelihood of severe disease and survival. The pandemic has fostered many nutrition-related theories, sometimes backed by a biased interpretation of evidence. To provide a systematic review of the latest evidence on how malnutrition across all its forms (under- and over-nutrition and micronutrient status) may influence both susceptibility to, and progression and severity of, COVID-19. We synthesised information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity and diabetes protein-energy malnutrition anaemia vitamins A, C, D, and E poly-unsaturated fatty acids iron selenium zinc anti-oxidants, and nutritional support. For each section we provide: a) a landscape review of pertinent material b) a systematic search of the literature in PubMed and EMBASE databases, including a systematic search of a wide range of pre-print servers and c) a screen of six clinical trial registries. Two reviewers were assigned per section for data extraction. All original research was considered, without restriction to study design, and included if it covered: 1) SARS-CoV-2, MERS-CoV or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 th May and 11 th August, 2020. PROSPERO registration CRD42020186194. Across the 13 searches, a total of 2732 articles from PubMed and EMBASE, 4164 articles from the pre-print servers, and 433 trials were returned. A total of 288 published articles and 278 pre-print articles were taken to full text screening. In the final narrative synthesis, we cover 22 published articles, 39 pre-print articles and 79 trials. The review highlights a range of mechanistic and observational evidence to highlight the role nutrition can play in susceptibility and progression of COVID-19. However, to date, there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery, although results of clinical trials are eagerly awaited. To date there is no conclusive evidence supporting adoption of novel nutritional therapies. However, given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. There is strong evidence that prevention of obesity, and its consequent type-2 diabetes, will reduce the risk of serious COVID-19 outcomes.
Publisher: Springer Science and Business Media LLC
Date: 03-12-2018
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-2019
Abstract: Inflammation from respiratory infections contributes to iron deficiency anemia in children by blocking iron absorption.
Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1093/JN/NXAB059
Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-05-2014
DOI: 10.1126/SCITRANSLMED.3008249
Abstract: The iron hormone hepcidin correctly identifies African children in whom iron supplementation is most likely to be beneficial.
Publisher: Public Library of Science (PLoS)
Date: 22-09-2015
Publisher: Springer Science and Business Media LLC
Date: 04-10-2019
DOI: 10.1038/S41467-019-12296-1
Abstract: Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts bone homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced bone destruction are poorly understood and current therapies do not restore lost bone mass. Using transcriptomic profiling of isolated bone lining cell subtypes from a murine myeloma model, we find that bone morphogenetic protein (BMP) signalling is upregulated in stromal progenitor cells. BMP signalling has not previously been reported to be dysregulated in myeloma bone disease. Inhibition of BMP signalling in vivo using either a small molecule BMP receptor antagonist or a solubilized BMPR1a-FC receptor ligand trap prevents trabecular and cortical bone volume loss caused by myeloma, without increasing tumour burden. BMP inhibition directly reduces osteoclastogenesis, increases osteoblasts and bone formation, and suppresses bone marrow sclerostin levels. In summary we describe a novel role for the BMP pathway in myeloma-induced bone disease that can be therapeutically targeted.
Publisher: Elsevier BV
Date: 19-04-2017
Publisher: American Society of Hematology
Date: 20-02-2020
Abstract: Erythroferrone (ERFE) is produced by erythroblasts in response to erythropoietin (EPO) and acts in the liver to prevent hepcidin stimulation by BMP6. Hepcidin suppression allows for the mobilization of iron to the bone marrow for the production of red blood cells. Aberrantly high circulating ERFE in conditions of stress erythropoiesis, such as in patients with β-thalassemia, promotes the tissue iron accumulation that substantially contributes to morbidity in these patients. Here we developed antibodies against ERFE to prevent hepcidin suppression and to correct the iron loading phenotype in a mouse model of β-thalassemia [Hbb(th3/+) mice] and used these antibodies as tools to further characterize ERFE’s mechanism of action. We show that ERFE binds to BMP6 with nanomolar affinity and binds BMP2 and BMP4 with somewhat weaker affinities. We found that BMP6 binds the N-terminal domain of ERFE, and a polypeptide derived from the N terminus of ERFE was sufficient to cause hepcidin suppression in Huh7 hepatoma cells and in wild-type mice. Anti-ERFE antibodies targeting the N-terminal domain prevented hepcidin suppression in ERFE-treated Huh7 cells and in EPO-treated mice. Finally, we observed a decrease in splenomegaly and serum and liver iron in anti–ERFE-treated Hbb(th3/+) mice, accompanied by an increase in red blood cells and hemoglobin and a decrease in reticulocyte counts. In summary, we show that ERFE binds BMP6 directly and with high affinity, and that antibodies targeting the N-terminal domain of ERFE that prevent ERFE–BMP6 interactions constitute a potential therapeutic tool for iron loading anemias.
Publisher: Wiley
Date: 17-01-2017
DOI: 10.1002/AJH.24617
Publisher: Proceedings of the National Academy of Sciences
Date: 04-08-2014
Abstract: Altered iron levels correlate with disease progression in HIV type-1 (HIV-1) infection, and cellular iron promotes HIV-1 replication. In chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, increased liver iron levels contribute to disease. The peptide hormone hepcidin controls iron distribution. We find that hepcidin increases during the acute phase of HIV-1 infection, early hepcidin predicts later plasma viral set-point, and hepcidin remains high even in chronically infected in iduals receiving antiretroviral therapy. Conversely hepcidin is not induced, and blood iron is not decreased, during the acute response to HBV and HCV. Therefore, the nature of iron redistribution during the response to infections is a pathogen-specific phenomenon furthermore, the deleterious effects of chronic infection on hepcidin and iron appear to be established early in infection.
Publisher: Oxford University Press (OUP)
Date: 07-2016
DOI: 10.1373/CLINCHEM.2016.256768
Abstract: Absolute plasma hepcidin concentrations measured by various procedures differ substantially, complicating interpretation of results and rendering reference intervals method dependent. We investigated the degree of equivalence achievable by harmonization and the identification of a commutable secondary reference material to accomplish this goal. We applied technical procedures to achieve harmonization developed by the Consortium for Harmonization of Clinical Laboratory Results. Eleven plasma hepcidin measurement procedures (5 mass spectrometry based and 6 immunochemical based) quantified native in idual plasma s les (n = 32) and native plasma pools (n = 8) to assess analytical performance and current and achievable equivalence. In addition, 8 types of candidate reference materials (3 concentrations each, n = 24) were assessed for their suitability, most notably in terms of commutability, to serve as secondary reference material. Absolute hepcidin values and reproducibility (intrameasurement procedure CVs 2.9%–8.7%) differed substantially between measurement procedures, but all were linear and correlated well. The current equivalence (intermeasurement procedure CV 28.6%) between the methods was mainly attributable to differences in calibration and could thus be improved by harmonization with a common calibrator. Linear regression analysis and standardized residuals showed that a candidate reference material consisting of native lyophilized plasma with cryolyoprotectant was commutable for all measurement procedures. Mathematically simulated harmonization with this calibrator resulted in a maximum achievable equivalence of 7.7%. The secondary reference material identified in this study has the potential to substantially improve equivalence between hepcidin measurement procedures and contributes to the establishment of a traceability chain that will ultimately allow standardization of hepcidin measurement results.
Publisher: American Society of Hematology
Date: 29-01-2015
DOI: 10.1182/BLOOD-2014-10-606491
Abstract: Expanded erythropoiesis strongly drives hepcidin suppression in severe transfusion-dependent HbE β-thalassemia. β-thalassemia carriers, but not HbE carriers, have enhanced erythropoiesis associated with mildly suppressed hepcidin.
Publisher: Elsevier BV
Date: 10-2015
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Andrew Armitage.