Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study

Duffy, Darragh; Rouilly, Vincent; Braudeau, Cécile; Corbière, Véronique; Djebali, Raouf; Ungeheuer, Marie Noëlle; Josien, Régis; LaBrie, Samuel; Lantz, Olivier; Louis, Delphine; Martı́nez-Cáceres, Eva; Mascart, Françoise; Morales, José J.G. Ruiz de; Ottone, Catherine; Redjah, Lydia; Salabert, Nina; Savenay, Alain; Schmolz, Manfred; Toubert, Antoine; Albert, M.

doi:10.1016/j.clim.2017.09.019

Cited by 69 publications

(77 citation statements)

References 21 publications

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“…Limitations of this study include the small number of healthy dogs included and the fact that these results need to be confirmed in diseased dogs. Whole blood was used rather than separated PBMC, because similar cytokine profiles after stimulation have been reported with both methods, there is less manipulation of blood which means less risk of contamination or cell activations, blood is a more physiological surrogate than PMBC and finally repeatability has been reported to be higher with whole blood than PBMC (Thurm & Halsey 2005;van Dooren et al 2013;Duffy et al 2017).…”

Section: <0001mentioning

confidence: 99%

Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12‐myristate 13‐acetate

Dandrieux

Narayanan

Firestone

et al. 2019

Veterinary Medicine & Sci

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A pharmacodynamic assay has been previously developed to monitor ciclosporin treatment in dogs by assessing inhibition of cytokine transcription after whole blood stimulation with 12‐myristate 13‐1 acetate and ionomycin ( PMA /I). In this study, whole blood stimulation with either PMA /I or lipopolysaccharide ( LPS ) was used to assess the effect of multiple drugs (azathioprine, ciclosporin, mycophenolate, leflunomide and prednisone) after a 7‐day treatment course on production of cytokines measured with a multiplex assay in healthy dogs ( n = 4 for each treatment). Interleukin‐10 ( IL ‐10), interferon gamma ( IFN γ ) and tumour necrosis factor alpha ( TNF α ) were significantly activated by PMA /I stimulation and IL ‐6, IL ‐10 and TNF α by LPS stimulation, in the absence of immunosuppressive drugs. After ciclosporin treatment, IL ‐10, IFN γ and TNF α production was significantly reduced after stimulation with PMA /I compared to pre‐treatment. After prednisone treatment, TNF α production was significantly reduced after stimulation with PMA /I or LPS compared to pre‐treatment. No significant change was observed after treatment with azathioprine, leflunomide or mycophenolate. This methodology may be useful to monitor dogs not only treated with ciclosporin, but also with prednisone or a combination of both. Further studies are needed to assess the use of this assay in a clinical setting.

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Section: <0001mentioning

confidence: 99%

Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12‐myristate 13‐acetate

Dandrieux

Narayanan

Firestone

et al. 2019

Veterinary Medicine & Sci

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“…Recently, we described a multi-center clinical study that directly compared TruCulture with conventional PBMCs, utilizing lipopolysaccharide (LPS) and combined anti-CD3/CD28 antibodies as the stimulants and Luminex multi-analyte proteins as the readout. 10 The major finding was the improved reproducibility of TruCulture as compared to PBMC stimulation, in particular, for inter-center differences highlighting the suitability of this approach for multi-center immunomonitoring studies. 10 Other groups have utilized similar standardized whole blood plate-based stimulations that require lower blood volumes, an advantage for pediatric studies.…”

Section: The Need For Standardized Immunomonitoringmentioning

confidence: 98%

“…10 The major finding was the improved reproducibility of TruCulture as compared to PBMC stimulation, in particular, for inter-center differences highlighting the suitability of this approach for multi-center immunomonitoring studies. 10 Other groups have utilized similar standardized whole blood plate-based stimulations that require lower blood volumes, an advantage for pediatric studies. 11 …”

Section: The Need For Standardized Immunomonitoringmentioning

confidence: 98%

Milieu intérieur: Defining the boundaries of a healthy immune response for improved vaccination strategies

Duffy

2018

Human Vaccines & Immunotherapeutics

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Immune responses in human populations are highly variable, with this variability presenting challenges for vaccine design. As such a better understanding of the factors that determine this variability will help in the development of precision vaccination strategies. The Milieu Interieur consortium was established to address this challenge through a definition of the normal boundaries of a healthy immune response, and the characterization of their genetic and environmental determinants. To do this we have implemented standardized tools for monitoring functional immune responses at the proteomic and transcriptional level, which have been applied to a 1,000 healthy donor cohort. This approach has recently allowed us to quantify the extent of genetic control of cellular variability and transcriptional responses to infection. Initial findings on the influence of age, sex, and genetics may already be included in considerations for improved vaccine development, and ongoing analysis will further define the factors behind inter-individual variability in diverse immune responses. This approach will help to guide the development of the next generation of vaccines that will take into account differences in populations and eventually individuals.

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“…Comparative Immunology, Microbiology and Infectious Diseases 59 (2018) [57][58][59][60][61][62] tb infection could help to overcome some important limitations of IGRAs, such as testing in young children or immunocompromised individuals [39,45,46]. This monokine-based reporter has been shown to be both sensitive and accurate in studying antigen-specific T cell responses.…”

Section: A Llibre D Duffymentioning

confidence: 99%

“…With the aim of improving the signal-to-noise in the context of disease diagnosis, two main strategies have been defined [3]. One involves the utilisation of more standardised approaches for studying induced immune approaches [60]; and a second complementary approach comprises the use of multiple cytokine markers detected with multiplex assays instead of a single analyte for the identification of more robust signatures [61]. In addition, studies that will define the genetic and environmental contributions to such naturally occurring variability to provide reference range values will help to better identify real biological signals from background noise [62].…”

Section: Conclusion and Remaining Challengesmentioning

confidence: 99%

Immune response biomarkers in human and veterinary research

Llibre

Duffy

2018

Comparative Immunology, Microbiology and Infectious Diseases

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A B S T R A C TBiomarkers are increasingly utilised in biological research and clinical practice for diagnosis of disease, monitoring of therapeutic prognosis, or as end points in clinical studies. Cytokines are small molecules that orchestrate immune responses and as such have great potential as biomarkers for both human and veterinary fields. Given the ease of sampling in the blood, and their high prevalence in clinical applications we will focus on protein detection as an area for biomarker discovery. This is facilitated by new technological developments such as digital ELISA that have led to significant increases in sensitivity. Two highly relevant examples include type I interferons, namely IFNα, that is now directly quantifiable by digital ELISA from biological samples. The application of this approach to the study of the unique bat interferon response may reveal novel findings with applications in both human and veterinary research. As a second example we will describe the use of CXCL10 as a disease biomarker in Tuberculosis, highlighting findings from human and mouse studies that should be considered in veterinary research. In summary, we describe how cytokines may be applied as novel biomarkers and illustrate two key examples where human and veterinary research may complement each other in line with the One Health objectives. Cytokines and Chemokines as immune response biomarkersBlood and plasma-borne biomarkers are not only desirable for their accessibility, but also because they offer the potential for serial monitoring. Unlike SNPs which are static, protein responses are dynamic and can therefore potentially reflect disease status or even responses to therapeutic intervention. Plasma carries information from most organs https://doi.

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Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study

Cited by 69 publications

References 21 publications

Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12‐myristate 13‐acetate

Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12‐myristate 13‐acetate

Milieu intérieur: Defining the boundaries of a healthy immune response for improved vaccination strategies

Immune response biomarkers in human and veterinary research

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