Publications by authors named "Daniel M Altmann"

Article Synopsis
  • Podoconiosis is a non-infectious tropical lymphoedema affecting around 4 million people, linked to HLA class II and triggered by unknown factors in volcanic red clay soils.
  • The study measured immune responses in podoconiosis patients by analyzing cytokine levels and gene expressions after exposure to specific minerals, finding that patients had higher baseline cytokine levels but lower responses to mineral stimulation.
  • The findings indicate ongoing immune activation in podoconiosis patients, highlighting the need for further research to understand immune dysfunction and potentially develop early detection methods for this preventable disease.
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Available evidences suggest that podoconiosis is triggered by long term exposure of bare feet to volcanic red clay soil particles. Previous genome-wide studies in Ethiopia showed association between the HLA class II region and disease susceptibility. However, functional relationships between the soil trigger, immunogenetic risk factors and the immunological basis of the disease are uncharted.

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The rapid evolution of COVID-19 Omicron variants is driven by evasion of neutralizing antibodies. Breakthrough infections are common, even in highly vaccinated populations, making it vital to understand immune cross-protective repertoires to variants. Two studies in this issue show that the primed T cell repertoire comprises strong cross-recognition of current variants.

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Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases.

Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK.

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Background And Aims: We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with inflammatory bowel disease [IBD].

Methods: We conducted a prospective study including 213 IBD patients and 53 healthy controls: 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab, or tofacitinib.

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We measured anti-SARS-CoV-2 antibody responses before and after CoronaVac (inactivated) vaccination in a case-control study performed in CoronaVac-immunized individuals participating in a longitudinal prospective study of adults in Manaus (DETECTCoV-19). Antibody responses were measured by standard serological immunoassays. Peak anti-S-RBD and neutralizing RBD-ACE2 blocking antibody responses after two doses of CoronaVac vaccine were similar in vaccine breakthrough cases ( = 9) and matched controls ( = 45).

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Background: Patients with inflammatory bowel disease (IBD) receiving anti-TNF and JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the Omicron BA.4/5 variant.

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Article Synopsis
  • The study investigates whether abnormal immune responses during acute SARS-CoV-2 infection contribute to Long Covid symptoms.
  • Researchers analyzed immune responses in 86 healthcare workers with mild or asymptomatic infections, focusing on antibody and T cell responses over time.
  • Findings indicate no significant differences in immune responses between individuals with persistent symptoms and those without, suggesting that immune response variations are unlikely to cause Long Covid.
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Background: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course.

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Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge.

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T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately.

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Background: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.

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The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA.

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Article Synopsis
  • A study analyzed the plasma proteome of 156 healthcare workers in the UK who had SARS-CoV-2 infections during the first wave, focusing on the relationship between the plasma proteins and the severity/duration of symptoms.
  • The researchers tracked 91 specific proteins before and after infection, finding that changes in the plasma proteome lasted up to 6 weeks post-infection and were linked to symptom severity and antibody responses.
  • Results indicated that specific protein changes were associated with persistent symptoms even 12 months later, suggesting these plasma proteome alterations could help understand the long-term effects of COVID-19.
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Article Synopsis
  • Researchers assessed immune response profiles in SARS-CoV-2 infected patients by examining 71 biomarkers across different clinical groups: asymptomatic, mild, and severe cases.
  • They found that certain angiogenesis and cardiovascular disease biomarkers were significantly elevated in severe cases compared to the other groups, indicating distinct immune profiles.
  • The study highlights important differences in cytokines and chemokines among patients, providing insights into potential prognostic markers for understanding disease severity in COVID-19 infections.
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Background: COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose.

Methods: VIP was a multicentre, prospective, case-control study done in nine centres in the UK.

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Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization.

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