Publications
161 results found
Evans D, Papadimitriou KI, Greathead L, et al., 2017, An Assay System for Point-of-Care Diagnosis of Tuberculosis using Commercially Manufactured PCB Technology, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
Rapid advances in clinical technologies, detection sensitivity and analytical throughput have delivered a significant expansion in our knowledge of prognostic and diagnostic biomarkers in many common infectious diseases, such as Tuberculosis (TB). During the last decade, a significant number of approaches to TB diagnosis have been attempted at Point-of-Care (PoC), exploiting a large variation of techniques and materials. In this work, we describe an electronics-based Enzyme-Linked ImmunoSorbent Assay (eELISA), using a Lab-on-a-Printed Circuit Board (LoPCB) approach, for TB diagnosis based on cytokine detection. The test relies upon an electrochemical (amperometric) assay, comprising a high-precision bioinstrumentation board and amperometric sensors, produced exclusively using standard PCB manufacturing processes. Electrochemical detection uses standard Au and Ag electrodes together with a bespoke, low-power, multichannel, portable data-acquisition system. We demonstrate high-performance assay chemistry performed at microfluidic volumes on Au pads directly at the PCB surface with improved limit of detection (~10 pg/mL) over standard colorimetric ELISA methods. The assay has also been implemented in plasma, showing the utility of the system for medical applications. This work is a significant step towards the development of a low-cost, portable, high-precision diagnostic and monitoring technology, which once combined with appropriate PCB-based microfluidic networks will provide complete LoPCB platforms.
Hurst JR, Verma N, Lowe D, et al., 2017, British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders., Journal of Allergy and Clinical Immunology: In Practice, Vol: 5, Pages: 938-945, ISSN: 2213-2198
A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).
Fraccaro A, Montero-Fernandez A, Nicholson AG, et al., 2017, Tissue Expression Of Th2 Markers: Comparison Between Idiopathic Pulmonary Fibrosis And Fibrotic Hypersensitivity Pneumonitis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Kelleher WP, 2016, Amperometric IFN-γ immunosensors with commercially fabricated PCB sensing electrodes, Biosensors & Bioelectronics, ISSN: 1873-4235
Moschou D, Greathead L, Pantelidis P, et al., 2016, Amperometric IFN-gamma immunosensors with commercially fabricated PCB sensing electrodes, BIOSENSORS & BIOELECTRONICS, Vol: 86, Pages: 805-810, ISSN: 0956-5663
Vera JH, Guo Q, Cole JH, et al., 2016, Neuroinflammation in treated HIV-positive individuals: A TSPO PET study, Neurology, Vol: 86, Pages: 1425-1432, ISSN: 1526-632X
OBJECTIVE: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). METHODS: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [(11)C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. RESULTS: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). CONCLUSIONS: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.
McFaul K, Guo J, Atkins E, et al., 2016, A novel method to assess the functional of the anti-HIV gp-41 antibody in acute HIV-1 infection, 22nd Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 27-27, ISSN: 1464-2662
Grover V, Kelleher P, Singh S, 2015, Temporal changes in monocytic and neutrophilic trem-1 and trem-2 surface receptors in blood and bronchoalveolar lavage fluid in the development and resolution of ventilator-associated pneumonia (vap), Intensive Care Medicine Experimental, Vol: 3, ISSN: 2197-425X
Schippers EE, Cooper N, Graham C, et al., 2015, IDENTIFICATION OF B CELL SUBSETS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA, 20th Congress of European-Hematology-Association, Publisher: FERRATA STORTI FOUNDATION, Pages: 302-302, ISSN: 0390-6078
Bamford A, Hart M, Lyall H, et al., 2015, The influence of paediatric HIV infection on circulating B cell subsets and CXCR5+ T helper cells, Clinical and Experimental Immunology, Vol: 181, Pages: 110-117, ISSN: 1365-2249
Antiretroviral therapy (ART) only partially restores HIV-induced alterations in lymphocyte populations. We assessed B and T cell phenotypes in a cohort of children from a single centre in the United Kingdom with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children (44 of 56) were on fully suppressive combination ART. Children with perinatally acquired HIV had significantly lower memory B and CD4+CD45RO+CXCR5+ [follicular T helper cell (Tfh)-like] T cell percentages. Detectable viraemia was associated with higher CD21– (activated and exhausted/tissue-like memory) B cells. A greater proportion of life spent on suppressive ART was associated with higher memory B cell percentages. These results suggest that early and sustained suppressive ART may preserve B and T cell phenotypes in perinatally acquired HIV and limit deficits in humoral immunity. A lower proportion of circulating Tfh-like cells in HIV infected children appears to be independent of HIV treatment history and ongoing HIV viraemia and warrants further investigation.
Benlahrech A, Duraisingham S, King D, et al., 2015, Human blood CD1c dendritic cells stimulate IL-12-independent IFN-γ responses and have a strikingly low inflammatory profile, JOURNAL OF LEUKOCYTE BIOLOGY, Vol: 97, Pages: 873-885, ISSN: 0741-5400
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- Citations: 15
Vera J, Winston A, Gunn R, et al., 2015, Microbial translocation is associated with neuroinflammation in HIV subjects on ART, Publisher: WILEY-BLACKWELL, Pages: 6-7, ISSN: 1464-2662
Rawson TM, Dubb S, Pozniak A, et al., 2015, Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study, INTERNATIONAL JOURNAL OF STD & AIDS, Vol: 26, Pages: 128-132, ISSN: 0956-4624
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- Citations: 5
Singh S, Grover V, Christie L, et al., 2015, A Comparative Study of Bronchoscopic Microsample Probe versus Bronchoalveolar Lavage in Patients with Burns-Related Inhalational Injury, Acute Lung Injury and Chronic Stable Lung Disease, RESPIRATION, Vol: 89, Pages: 19-26, ISSN: 0025-7931
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- Citations: 13
Page EE, Greathead L, Metcalf R, et al., 2014, Loss of Th22 Cells Is Associated With Increased Immune Activation and IDO-1 Activity in HIV-1 Infection, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 67, Pages: 227-235, ISSN: 1525-4135
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- Citations: 32
Grover V, Pantelidis P, Soni N, et al., 2014, A biomarker panel (Bioscore) incorporating monocytic surface and soluble TREM-1 has high discriminative value for ventilator-associated pneumonia: a prospective observational study, PLOS One, Vol: 9, ISSN: 1932-6203
Schuetz K, Grimbacher B, Haddock J, et al., 2014, A Multicentre Approach to Document Bronchial Pathology in Computed Tomography of the Chest: Data from the Chest CT in Antibody-Deficiency Group, 16th Biennial Meeting of the European-Society-for-Immunodeficiencies, Publisher: SPRINGER/PLENUM PUBLISHERS, Pages: S323-S324, ISSN: 0271-9142
Bamford A, Kelleher P, Lyall H, et al., 2014, Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection, AIDS, Vol: 28, Pages: 2033-2043, ISSN: 0269-9370
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- Citations: 20
Greathead L, Metcalf R, Gazzard B, et al., 2014, CD8(+)/CD161(++) mucosal-associated invariant T-cell levels in the colon are restored on long-term antiretroviral therapy and correlate with CD8(+) T-cell immune activation, AIDS, Vol: 28, Pages: 1690-1692, ISSN: 0269-9370
Mucosal-associated invariant T (MAIT) cells are tissue-homing T cells recently implicated in HIV pathogenesis. We found that the proportion of MAIT cell in blood and colon of HIV+ patients are reduced in untreated infection. Antiretroviral therapy restored colonic but not blood MAIT cell percentages. We observed a negative correlation between colonic MAIT cells and T-cell activation in blood and suggest mucosal MAIT cell depletion may contribute to systemic immune activation in HIV infection.
Paraskevopoulou S, Pantelidis P, Mistry H, et al., 2014, Comparison of the Roche Cobas Ampliprep/Taqman HIV 1 test V2.0 assay to Siemens HIV 1 RNA 3.0 bDNA analyser, the VERSANT 440 Molecular system, HIV MEDICINE, Vol: 15, Pages: 96-96, ISSN: 1464-2662
Dubb S, Rawson T, Mandalia S, et al., 2014, MSM Neurocog: Role of peripheral CD8 T cells in neurocognitive screening test outcome, HIV MEDICINE, Vol: 15, Pages: 76-76, ISSN: 1464-2662
Herath S, Benlahrech A, Papagatsias T, et al., 2014, Fusion of Ubiquitin to HIV Gag Impairs Human Monocyte-Derived Dendritic Cell Maturation and Reduces Ability to Induce Gag T Cell Responses, PLOS ONE, Vol: 9, ISSN: 1932-6203
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- Citations: 5
de Lavallade H, Khoder A, Hart M, et al., 2013, Tyrosine kinase inhibitors impair B-cell immune responses in CML through off-target inhibition of kinases important for cell signaling, BLOOD, Vol: 122, Pages: 227-238, ISSN: 0006-4971
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- Citations: 83
Wells AU, Kelleher WP, 2013, Idiopathic Pulmonary Fibrosis Pathogenesis and Novel Approaches to Immunomodulation We Must Not Be Tyrannized by the PANTHER Data, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, Pages: 677-679, ISSN: 1073-449X
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- Citations: 7
Wells AU, Kelleher WP, 2013, Idiopathic pulmonary fibrosis pathogenesis and novel approaches to immunomodulation: we must not be tyrannized by the PANTHER data., Am J Respir Crit Care Med, Vol: 187, Pages: 677-679
Benlahrech A, Yasmin A, Westrop S, et al., 2013, Antiretroviral therapy restores HIV-1-induced abnormal expression of immunoregulatory molecules by plasmacytoid DC, HIV MEDICINE, Vol: 14, Pages: 25-25, ISSN: 1464-2662
Chen J, Benlahrech A, Kelleher P, et al., 2013, Increased Activity of Extrinsic and Intrinsic Apoptosis Pathways in Different Mononuclear Cell Types in HIV Type 1-Infected Patients Regardless of Whether They Are Depleted in Disease, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 29, Pages: 709-717, ISSN: 0889-2229
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- Citations: 3
De Lauretis A, Sestini P, Pantelidis P, et al., 2013, Serum Interleukin 6 Is Predictive of Early Functional Decline and Mortality in Interstitial Lung Disease Associated with Systemic Sclerosis, JOURNAL OF RHEUMATOLOGY, Vol: 40, Pages: 435-446, ISSN: 0315-162X
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- Citations: 180
Page E, Greathead L, Hart M, et al., 2013, Alterations in the balance of Th1 (CXCR3+CCR5+) cells to Th17 (CCR4+CCR6+CCR10-) and Th22 (CCR4+CCR6+CCR10+) cells in HIV-1/HCV coinfection is associated with immune activation, microbial translocation and liver fibrosis, HIV MEDICINE, Vol: 14, Pages: 3-3, ISSN: 1464-2662
Metcalf R, Kelleher P, 2013, TB vaccines in the era of HIV: New developments, CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources, Vol: 8
Mycobacterium tuberculosis (M.tb) infection is a global problem, which is exacerbated by human immunodeficiency virus-1 (HIV-1) co-infection. Despite the use of the Bacillus Calmette-Guérin (BCG) vaccine for over a century, it is evident that a new vaccine is needed because of its limitations in efficacy against tuberculosis (TB) and concerns about its safety in HIV-1-infected individuals. The complications of immune deficiency in HIV-1 patients must be taken into account when developing a vaccine suitable for this population. Although there have been no new vaccines since BCG, there are a number of vaccines in the pipeline, some of which have undergone safety and efficacy tests in clinical trials in HIV-1-infected patients. In this review, we will summarize the interactions between HIV-1 and TB and their effects on the immune system and review the development of new TB vaccines and their use in patients with HIV-1 infection. © 2013 CAB International.
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