377 results on '"Goddard, Sarah"'
Search Results
352. Interleukin-10 Secretion Differentiates Dendritic Cells from Human Liver and Skin
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Goddard, Sarah, Youster, Janine, Morgan, Emma, and Adams, David H.
- Abstract
Liver dendritic cells (DCs), which may orchestrate the liver's unique immunoregulatory functions, remain poorly characterized. We used a technique of overnight migration from pieces of normal human liver and skin to obtain tissue-derived DCs with minimal culture and no additional cytokine treatment. Liver and skin DCs had a monocyte-like morphology and a partially mature phenotype, expressing myeloid markers, MHCII, and co-stimulatory molecules; but only the skin DCs contained a population of CD1a+ cells. Overnight-migrated liver DCs activated naïve cord blood T cells efficiently. Liver DCs produced interleukin (IL)-10 whereas skin DCs failed to secrete IL-10 even after stimulation and neither skin nor liver-derived DCs secreted significant amounts of IL-12p70. Compared with skin DCs, liver DCs were less effective at stimulating T-cell proliferation and stimulated T cells to produce IL-10 and IL-4 whereas skin DCs were more potent stimulators of interferon-γ and IL-4. Monocyte-derived DCs were down-regulated after culture with liver-conditioned media, suggesting that local microenvironmental factors may be important. Thus we show for the first time clear tissue-specific differences in nonlymphoid DCs. Although it is not possible to conclude from our data whether liver DCs are more regulatory, or skin DCs more proimmunogenic, the ability of liver DCs to secrete IL-10 may be important for regulating local immune responses within the liver in the face of constant exposure to gut antigens.
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- 2004
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353. Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort
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Thaventhiran, James E. D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H. R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V. V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Lyons, Paul A., Hurles, Matthew E., Savic, Sinisa, Burns, Siobhan O., Kuijpers, Taco W., Turro, Ernest, Ouwehand, Willem H., Thrasher, Adrian J., and Smith, Kenneth G. C.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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354. Run with it.
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Goddard, Sarah
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FLAGSHIP stores ,BUSINESS expansion - Abstract
The article presents information on a new flagship store of ASICS Corp. at Amsterdam, Netherlands. ASICS was founded in Kobe, Japan about 60 years ago. The original store design concept of ASICS was developed by Formation Inc. ASICS Europe retail team collaborated with Wests Design Consultants to adapt the design concept for the Amsterdam store.
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- 2011
355. Methylprednisolone therapy for acute rejection: Too much of a good thing?
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Goddard, Sarah and Adams, David H.
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- 2002
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356. An investigation into the role of endothelial cells and dendritic cells in the events leading to allograft tolerance or rejection following liver transplantation
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Goddard, Sarah
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- 616, Chemokine receptors
- Published
- 2002
357. Prolonged viral shedding following COVID-19 infection in a rheumatoid patient on rituximab treatment.
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Zahid, Aqsa, Fahim, Ahmed, Gupta, Latika, Adenitan, Ajibade, Sheeran, Tom, and Goddard, Sarah
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VIRAL load , *DISEASE duration , *RHEUMATOID arthritis , *IMMUNOCOMPROMISED patients , *COVID-19 testing , *RITUXIMAB , *TREATMENT effectiveness , *ORAL drug administration , *ANTIVIRAL agents , *COVID-19 - Abstract
The article presents a case study of a 50-year-old woman with rheumatoid arthritis undergoing rituximab treatment, who experienced prolonged COVID-19 infection. It details her initial conservative treatment and subsequent complications, including a high-grade fever and bacterial infection, followed by a diagnosis of organizing pneumonia. It is reported that despite treatment, COVID-19 PCR remained positive five months later, and an antibody assay showed no detectable COVID-19 antibodies.
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- 2024
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358. Your Say.
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Eckersley, Stanley, White, George, Dodd, Pete, and Goddard, Sarah
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Several letters to the editor are presented in response to articles in previous issues including "Going downhill fast," by Nick Swinburn in the October 21, 2010 issue, another about television broadcasting of sports in Great Britain, and another one on the periodical's coverage of the Commonwealth Games.
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- 2010
359. SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study.
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Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Al-Taei, Saly, Tanner, Chloe, Ashford, Fiona, Workman, Sarita, Moreira, Fernando, Verma, Nisha, Wagg, Hollie, Heritage, Gail, Campton, Naomi, Stamataki, Zania, Klenerman, Paul, Thaventhiran, James E. D., Goddard, Sarah, Johnston, Sarah, Huissoon, Aarnoud, Bethune, Claire, and Elcombe, Suzanne
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COVID-19 vaccines , *VACCINE effectiveness , *BREAKTHROUGH infections , *ANTIBODY formation , *PRIMARY immunodeficiency diseases - Abstract
Background: Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives: COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods: Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results: A total of 5.6% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n = 168) compared with 100% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion: SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection. [ABSTRACT FROM AUTHOR]
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- 2022
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360. 108 PU.1-associated inborn errors of immunity: new mutations, phenotypes, and inheritance patterns.
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Knox, Ainsley, Platt, Craig, Casanova, Jean-Laurent, Seppänen, Mikko, Sullivan, Kathleen, Dutmer, Cullen, Goddard, Sarah, James, Elliot, Dhamija, Radhika, Shinawi, Marwan, Barzaghi, Federica, Boztug, Kaan, Rosenzweig, Sergio, Stojanovic, Maja, Grönholm, Juha, Arlabosse, Tiphaine, Esty, Brittany, Broides, Arnon, Boisson, Bertrand, and Romberg, Neil
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PHENOTYPES , *HEREDITY , *IMMUNITY , *AGAMMAGLOBULINEMIA , *TRANSCRIPTION factors - Published
- 2024
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361. Hepatitis C is associated with perturbation of intrahepatic myeloid and plasmacytoid dendritic cell function
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Lai, Wai Kwan, Curbishley, Stuart M., Goddard, Sarah, Alabraba, Edward, Shaw, Jean, Youster, Janine, McKeating, Jane, and Adams, David H.
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HEPATITIS C , *DENDRITIC cells , *VIRAL hepatitis , *IMMUNE response - Abstract
Background/Aims: In most cases infection with hepatitis C results in chronic infection as a consequence of viral subversion and failed anti-viral immune responses. The suggestion that dendritic cells are defective in chronic HCV infection led us to investigate the phenotype and function of liver-derived myeloid (mDC) and plasmacytoid (pDC) dendritic cells in patients with chronic HCV infection. Methods: Liver DCs were isolated without expansion in cytokines from human liver allowing us to study unmanipulated tissue-resident DCs ex vivo. Results: Compared with mDCs isolated from non-infected inflamed liver mDCs from HCV-infected liver (a) demonstrated higher expression of MHC class II, CD86 and CD123, (b) were more efficient stimulators of allogeneic T-cells and (c) secreted less IL-10. Reduced IL-10 secretion may be a factor in the enhanced functional properties of mDCs from HCV infected liver because antibody depletion of IL-10 enhanced the ability of mDCs from non-infected liver to stimulate T-cells. In contrast, pDCs were present at lower frequencies in HCV-infected liver and expressed higher levels of the regulatory receptor BDCA-2. Conclusions: In HCV-infected liver the combination of enhanced mDC function and a reduced number of pDCs may contribute to viral persistence in the face of persistent inflammation. [Copyright &y& Elsevier]
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- 2007
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362. "O"riginal design.
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Goddard, Sarah
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RETAIL store design & construction - Abstract
The article focuses on the launch of one of Oakley Inc.'s Optic O Store located in Pembroke, Florida, wherein the store design, which was developed by Tajima Creative, looks like an art gallery.
- Published
- 2012
363. Oil canvas.
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Goddard, Sarah
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ARCHITECTURAL design - Abstract
The article discusses the architectural design of TA-ZE store, a premium olive oil store in Toronto, Canada, by interior design firm Burdifilek.
- Published
- 2012
364. Fruits of design.
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Goddard, Sarah
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RETAIL stores - Abstract
The article offers information on the design of RK Apothecary's new retail store focused on nature in Santa Monica, California.
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- 2010
365. Yoga for Stress Reduction: Simple Techniques to Manage and Release Stress.
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Goddard, Sarah
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DVD-Video discs ,YOGA - Abstract
A review of the DVD release "Yoga for Stress Reduction: Simple Techniques to Manage and Release Stress," by Hala Khouri is presented.
- Published
- 2011
366. Current Practices and Considerations in Lung Biopsy for Suspected Granulomatous-Lymphocytic Interstitial Lung Disease: A Clinician Survey.
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Bintalib HM, Davidsen JR, Van de Ven AAJM, Goddard S, Burns SO, Warnatz K, and Hurst JR
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Introduction: This study explores clinicians' diagnostic practices and perceptions in the context of granulomatous-lymphocytic interstitial lung disease (GLILD), a pulmonary manifestation of common variable immunodeficiency disorder. The aim was to gain valuable insights into key aspects, such as the utilization of radiological features for diagnostic purposes, indications for lung biopsy, preferred biopsy techniques, and the relative importance of different histopathological findings in confirming GLILD., Method: A survey targeting expert clinicians was conducted, focusing on their experiences, practices, and attitudes towards lung biopsy in suspected GLILD cases., Results: The survey revealed that the majority of respondents accepted high-resolution computed tomography as a sufficient alternative to biopsy for making a probable GLILD diagnosis in most patients. There was a consensus among most respondents that the presence of extrapulmonary granulomatous disease is adequate for making a diagnosis of GLILD where the chest imaging and clinical picture are consistent. When a biopsy was recommended, there was notable variation in the preferred initial biopsy technique, with 35% favouring transbronchial biopsy., Conclusion: Our findings underscore the complexity of diagnosing GLILD, indicating varied clinician opinions on the necessity and efficacy of lung biopsies. They highlight the need for further research and the development of consistent diagnostic criteria and management protocols, ultimately aiming to enhance the accuracy and safety of GLILD diagnosis and treatment strategies., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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367. A National Survey of Hereditary Angioedema and Acquired C1 Inhibitor Deficiency in the United Kingdom.
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Yong PFK, Coulter T, El-Shanawany T, Garcez T, Hackett S, Jain R, Kiani-Alikhan S, Manson A, Noorani S, Stroud C, Symons C, Sargur R, Steele C, Alachkar H, Anantharachagan A, Arkwright PD, Bernatoniene J, Bhole M, Brown L, Buckland M, Burns S, Chopra C, Darroch J, Drewe E, Edmonds J, Ekbote A, Elkhalifa S, Goddard S, Grosse-Kreul D, Gurugama P, Hague R, Herriot R, Herwadkar A, Hughes SM, Jones L, Lear S, McDermott E, Kham Murng SH, Price A, Redenbaugh V, Richter A, Riordan A, Shackley F, Stichbury J, Springett D, Tarzi MD, Thomas M, Vijayadurai P, and Worth A
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- Humans, Female, Male, Complement C1 Inhibitor Protein therapeutic use, Danazol therapeutic use, United Kingdom epidemiology, Surveys and Questionnaires, Angioedemas, Hereditary epidemiology, Angioedemas, Hereditary drug therapy
- Abstract
Background: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care., Objective: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients., Methods: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data., Results: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home., Conclusions: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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368. Dose reductions in immunoglobulin replacement are associated with increased antibiotic usage in patients with antibody deficiency.
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Elhaj MO, Richter AG, Goddard S, and Shields AM
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- Humans, Drug Tapering, Immunoglobulins, Intravenous therapeutic use, Anti-Bacterial Agents therapeutic use, Immunologic Deficiency Syndromes drug therapy
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- 2023
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369. Prevalence of CFTR variants in primary immunodeficiency patients with bronchiectasis is an important modifying cofactor.
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Lawless D, Allen HL, Thaventhiran JED, Goddard S, Burren OS, Robson E, Peckham D, Smith KGC, and Savic S
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- Humans, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Prevalence, Mutation, Bronchiectasis epidemiology, Bronchiectasis genetics, Cystic Fibrosis epidemiology, Cystic Fibrosis genetics
- Abstract
Background: Cystic fibrosis (CF) is one of the most common life-limiting autosomal-recessive disorders and is caused by genetic defects in the CF transmembrane conductance regulator (CFTR) gene. Some of the features of this multisystem disease can be present in primary immunodeficiency (PID)., Objective: We hypothesized that a carrier CFTR status might be associated with worse outcome regarding structural lung disease in patients with PID., Methods: A within-cohort and population-level statistical genomic analysis of a large European cohort of PID patients was performed using genome sequence data. Genomic analysis of variant pathogenicity was performed., Results: Compared to the general population, p.Phe508del carriage was enriched in lung-related PID. Additionally, carriage of several pathogenic CFTR gene variants were increased in PID associated with structural lung damage compared to PID patients without the structural lung damage. We identified 3 additional biallelic cases, including several variants not traditionally considered to cause CF., Conclusion: Genome sequencing identified cases of CFTR dysfunction in PID, driving an increased susceptibility to infection. Large national genomic services provide an opportunity for precision medicine by interpreting subtle features of genomic diversity when treating traditional Mendelian disorders., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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370. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.
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Shields AM, Anantharachagan A, Arumugakani G, Baker K, Bahal S, Baxendale H, Bermingham W, Bhole M, Boules E, Bright P, Chopra C, Cliffe L, Cleave B, Dempster J, Devlin L, Dhalla F, Diwakar L, Drewe E, Duncan C, Dziadzio M, Elcombe S, Elkhalifa S, Gennery A, Ghanta H, Goddard S, Grigoriadou S, Hackett S, Hayman G, Herriot R, Herwadkar A, Huissoon A, Jain R, Jolles S, Johnston S, Khan S, Laffan J, Lane P, Leeman L, Lowe DM, Mahabir S, Lochlainn DJM, McDermott E, Misbah S, Moghaddas F, Morsi H, Murng S, Noorani S, O'Brien R, Patel S, Price A, Rahman T, Seneviratne S, Shrimpton A, Stroud C, Thomas M, Townsend K, Vaitla P, Verma N, Williams A, Burns SO, Savic S, and Richter AG
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- Humans, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Antibodies, Viral, COVID-19 Serotherapy, Dexamethasone, Drug Combinations, Immunization, Passive, SARS-CoV-2, United Kingdom epidemiology, COVID-19 therapy, COVID-19 Drug Treatment, Immunologic Deficiency Syndromes
- Abstract
In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.)
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- 2022
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371. Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience.
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Shields AM, Tadros S, Al-Hakim A, Nell JM, Lin MMN, Chan M, Goddard S, Dempster J, Dziadzio M, Patel SY, Elkalifa S, Huissoon A, Duncan CJA, Herwadkar A, Khan S, Bethune C, Elcombe S, Thaventhiran J, Klenerman P, Lowe DM, Savic S, Burns SO, and Richter AG
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- Humans, Antibodies, Monoclonal, Antiviral Agents, COVID-19 Vaccines, Hospitalization, SARS-CoV-2 genetics, Seroepidemiologic Studies, Vaccination, COVID-19 epidemiology
- Abstract
Background: Individuals with primary and secondary immunodeficiency (PID/SID) were shown to be at risk of poor outcomes during the early stages of the SARS-CoV-2 pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients., Objectives: To understand whether the risk of severe COVID-19 in individuals with PID or SID has changed following the deployment of vaccination and therapeutics in the context of the emergence of novel viral variants of concern., Methods: The outcomes of two cohorts of patients with PID and SID were compared: the first, infected between March and July 2020, prior to vaccination and treatments, the second after these intervention became available between January 2021 and April 2022., Results: 22.7% of immunodeficient patients have been infected at least once with SARS-CoV-2 since the start of the pandemic, compared to over 70% of the general population. Immunodeficient patients were typically infected later in the pandemic when the B.1.1.529 (Omicron) variant was dominant. This delay was associated with receipt of more vaccine doses and higher pre-infection seroprevalence. Compared to March-July 2020, hospitalization rates (53.3% vs 17.9%, p<0.0001) and mortality (Infection fatality rate 20.0% vs 3.4%, p=0.0003) have significantly reduced for patients with PID but remain elevated compared to the general population. The presence of a serological response to vaccination was associated with a reduced duration of viral detection by PCR in the nasopharynx. Early outpatient treatment with antivirals or monoclonal antibodies reduced hospitalization during the Omicron wave., Conclusions: Most individuals with immunodeficiency in the United Kingdom remain SARS-CoV-2 infection naïve. Vaccination, widespread availability of outpatient treatments and, possibly, the emergence of the B.1.1.529 variant have led to significant improvements in morbidity and mortality followings SARS-CoV-2 infection since the start of the pandemic. However, individuals with PID and SID remain at significantly increased risk of poor outcomes compared to the general population; mitigation, vaccination and treatment strategies must be optimized to minimize the ongoing burden of the pandemic in these vulnerable cohorts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shields, Tadros, Al-Hakim, Nell, Lin, Chan, Goddard, Dempster, Dziadzio, Patel, Elkalifa, Huissoon, Duncan, Herwadkar, Khan, Bethune, Elcombe, Thaventhiran, Klenerman, Lowe, Savic, Burns and Richter.)
- Published
- 2022
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372. Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study.
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Shields AM, Faustini SE, Hill HJ, Al-Taei S, Tanner C, Ashford F, Workman S, Moreira F, Verma N, Wagg H, Heritage G, Campton N, Stamataki Z, Drayson MT, Klenerman P, Thaventhiran JED, Elkhalifa S, Goddard S, Johnston S, Huissoon A, Bethune C, Elcombe S, Lowe DM, Patel SY, Savic S, Richter AG, and Burns SO
- Subjects
- Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, ChAdOx1 nCoV-19, Humans, SARS-CoV-2, Seroepidemiologic Studies, Vaccination, COVID-19, Viral Vaccines
- Abstract
Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity., Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency., Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays., Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%)., Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shields, Faustini, Hill, Al-Taei, Tanner, Ashford, Workman, Moreira, Verma, Wagg, Heritage, Campton, Stamataki, Drayson, Klenerman, Thaventhiran, Elkhalifa, Goddard, Johnston, Huissoon, Bethune, Elcombe, Lowe, Patel, Savic, Richter, Burns and the COV-AD consortium.)
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- 2022
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373. Impact of stopping long-term immunoglobulin therapy in patients with secondary antibody deficiency due to haematological disease.
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Goddard S, Diwakar L, Hughes D, Clarke D, and Graham J
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- Aged, Aged, 80 and over, Clinical Trials as Topic, Female, Hematologic Diseases complications, Hematology ethics, Humans, Immunoglobulin G analysis, Immunologic Deficiency Syndromes etiology, Male, Middle Aged, Patient Selection, Practice Guidelines as Topic, Retrospective Studies, United Kingdom epidemiology, Immunization, Passive adverse effects, Immunologic Deficiency Syndromes therapy, Withholding Treatment statistics & numerical data
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- 2021
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374. Whole-genome sequencing of a sporadic primary immunodeficiency cohort.
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Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D, Staples E, Zhang Z, Farmery JHR, Simeoni I, Rivers E, Maimaris J, Penkett CJ, Stephens J, Deevi SVV, Sanchis-Juan A, Gleadall NS, Thomas MJ, Sargur RB, Gordins P, Baxendale HE, Brown M, Tuijnenburg P, Worth A, Hanson S, Linger RJ, Buckland MS, Rayner-Matthews PJ, Gilmour KC, Samarghitean C, Seneviratne SL, Sansom DM, Lynch AG, Megy K, Ellinghaus E, Ellinghaus D, Jorgensen SF, Karlsen TH, Stirrups KE, Cutler AJ, Kumararatne DS, Chandra A, Edgar JDM, Herwadkar A, Cooper N, Grigoriadou S, Huissoon AP, Goddard S, Jolles S, Schuetz C, Boschann F, Lyons PA, Hurles ME, Savic S, Burns SO, Kuijpers TW, Turro E, Ouwehand WH, Thrasher AJ, and Smith KGC
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- Actin-Related Protein 2-3 Complex genetics, Bayes Theorem, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Primary Immunodeficiency Diseases diagnosis, Primary Immunodeficiency Diseases immunology, Protein Tyrosine Phosphatase, Non-Receptor Type 2 genetics, RNA-Binding Proteins genetics, Regulatory Sequences, Nucleic Acid genetics, Suppressor of Cytokine Signaling 1 Protein genetics, Transcription Factors genetics, Primary Immunodeficiency Diseases genetics, Whole Genome Sequencing
- Abstract
Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies
1-3 . Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4 ) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of-and interplay between-novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.- Published
- 2020
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375. Monitoring Menstrual Health in the Sustainable Development Goals
- Author
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Loughnan L, Mahon T, Goddard S, Bain R, Sommer M, Bobel C, Winkler IT, Fahs B, Hasson KA, Kissling EA, and Roberts TA
- Abstract
This chapter offers a systematic overview of the strong but currently under-recognized relationship between menstrual health and the main monitoring framework of progress in global development 2015–2030: the Sustainable Development Goals (SDGs). Looking at the overarching principles and intent of the SDG framework, and then goal by goal, the authors draw out particular SDG indicators to explain how monitoring met and unmet needs for menstrual health is essential to planning for SDG success. This chapter then describes some of the major data collection efforts that operate at-scale and could most readily provide new avenues for monitoring progress on menstrual health. The chapter concludes by outlining a way forward to strengthen monitoring and accountability for menstrual health during the SDG era., (Copyright 2020, The Author(s).)
- Published
- 2020
- Full Text
- View/download PDF
376. Mutation in the TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ+ T cells.
- Author
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Morgan NV, Goddard S, Cardno TS, McDonald D, Rahman F, Barge D, Ciupek A, Straatman-Iwanowska A, Pasha S, Guckian M, Anderson G, Huissoon A, Cant A, Tate WP, Hambleton S, and Maher ER
- Subjects
- Base Sequence, Child, Preschool, DNA Mutational Analysis, HeLa Cells, Humans, Molecular Sequence Data, Pedigree, Polymorphism, Single Nucleotide, Receptors, Antigen, T-Cell, alpha-beta metabolism, T-Lymphocytes cytology, Immunologic Deficiency Syndromes genetics, Immunologic Deficiency Syndromes immunology, Mutation, Receptors, Antigen, T-Cell, alpha-beta genetics, T-Lymphocytes immunology
- Abstract
Inherited immunodeficiency disorders can be caused by mutations in any one of a large number of genes involved in the function of immune cells. Here, we describe two families with an autosomal recessive inherited immunodeficiency disorder characterized by increased susceptibility to infection and autoimmunity. Genetic linkage studies mapped the disorder to chromosomal region 14q11.2, and a homozygous guanine-to-adenine substitution was identified at the last base of exon 3 immediately following the translational termination codon in the TCRα subunit constant gene (TRAC). RT-PCR analysis in the two affected individuals revealed impaired splicing of the mRNA, as exon 3 was lost from the TRAC transcript. The mutant TCRα chain protein was predicted to lack part of the connecting peptide domain and all of the transmembrane and cytoplasmic domains, which have a critical role in the regulation of the assembly and/or intracellular transport of TCR complexes. We found that T cells from affected individuals were profoundly impaired for surface expression of the TCRαβ complex. We believe this to be the first report of a disease-causing human TRAC mutation. Although the absence of TCRαβ+ T cells in the affected individuals was associated with immune dysregulation and autoimmunity, they had a surprising level of protection against infection.
- Published
- 2011
- Full Text
- View/download PDF
377. New approaches to immunosuppression in liver transplantation.
- Author
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Goddard S and Adams DH
- Subjects
- Animals, Antigen-Presenting Cells immunology, Apoptosis immunology, Graft Rejection immunology, Graft Rejection prevention & control, Humans, Immune Tolerance, Liver immunology, Immunosuppression Therapy methods, Immunosuppressive Agents administration & dosage, Liver Transplantation immunology
- Abstract
With the continued improvements in outcome following liver transplantation, the drawbacks associated with conventional immunosuppression regimens become increasingly apparent. Although up to 70% of patients develop a histological infiltrate of the graft (acute rejection), many of these will resolve spontaneously, and chronic rejection is rare. If a robust form of allograft acceptance or tolerance can be established, then immunosuppression can be withdrawn along with all the accompanying risks. The liver is already known to be associated with downregulated immune responses; the mechanism for this is unclear, but may be related to a number of mechanisms known to be involved in peripheral tolerance. There are many strategies being studied for achieving allograft tolerance, including the use of modern immunosuppressants, antibodies that target key molecules in the immune response, and recruitment of leukocytes to allografts. In the interim, it is necessary to look for safe protocols that allow trials of tolerance strategies without putting patients at increased risk.
- Published
- 2002
- Full Text
- View/download PDF
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