Biomarker-guided stratification of autoimmune patients for biologic therapy

Ivison, Sabine; Rosiers, Christine Des; Lesage, Sylvie; Rioux, John D.; Levings, Megan K.

doi:10.1016/j.coi.2017.09.006

Cited by 7 publications

(7 citation statements)

References 68 publications

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“…As for clinical tests, the use of PBMCs freshly prepared, unlike cryopreserved PBMCs, would most likely help reduce or control for technical variability and identify the biologic difference between samples. In this sense, variability in immune‐based assays is often observed following PBMC cryopreservation, including the detection of higher frequencies of cytokine‐producing cells when ex vivo versus cryopreserved PBMCs are stimulated with diverse antigens . The impact of cryopreservation can be minimized with innovative cell culture approaches that use ex vivo stimulation of blood cells with immune stimuli at the point of care and subsequent cytokine quantification in stored supernatants, eliminating the need for cell cryopreservation and help support harmonization of clinical studies and data sharing across multiple sites .…”

Section: Why When and How To Evaluate Cytokines?mentioning

confidence: 99%

The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

Nézondet

Poubelle

Pelletier

2020

Journal of Leukocyte Biology

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Our knowledge of the role of cytokines in pathologic conditions has increased considerably with the emergence of molecular and genetic studies, particularly in the case of autoinflammatory monogenic diseases. Many rare disorders, considered orphan until recently, are directly related to abnormal gene regulation, and the treatment with biologic agents (biologics) targeting cytokine receptors, intracellular signaling or specific cytokines improve the symptoms of an increasing number of chronic inflammatory diseases. As it is currently impossible to systematically conduct genetic studies for all patients with autoinflammatory and autoimmune diseases, the evaluation of cytokines can be seen as a simple, less time consuming, and less expensive alternative. This approach could be especially useful when the diagnosis of syndromes of diseases of unknown etiology remains problematic. The evaluation of cytokines could also help avoid the current trial-and-error approach, which has the disadvantages of exposing patients to ineffective drugs with possible unnecessary side effects and permanent organ damages. In this review, we discuss the various possibilities, as well as the limitations of evaluating the cytokine profiles of patients suffering from autoinflammatory and autoimmune diseases, with methods such as direct detection of cytokines in the plasma/serum or following ex vivo stimulation of PBMCs leading to the production of their cytokine secretome. The patients' secretome, combined with biomarkers ranging from genetic and epigenetic analyses to immunologic biomarkers, may help not only the diagnosis but also guide the choice of biologics for more efficient and rapid treatments.

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Section: Why When and How To Evaluate Cytokines?mentioning

confidence: 99%

The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

Nézondet

Poubelle

Pelletier

2020

Journal of Leukocyte Biology

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“…Survival analysis and risk prediction will be done with R using the packages 'survival' and 'Mangrove', respectively. For integrated biomarker discovery, 54 this genetic data will also be integrated with other biomarker data generated from the various IMAGINE platforms, in order to select those that estimate a large association with clinical outcomes (eg, response to therapy), in order to create the best subset of predictors. Variable selection will be based on mathematical criteria for model selection, that is, the Bayesian Information Criteria (BIC), and expert a priori (eg, clinical knowledge, preliminary evidence).…”

Section: Genetic Analysesmentioning

confidence: 99%

IMAGINE Network’s Mind And Gut Interactions Cohort (MAGIC) Study: a protocol for a prospective observational multicentre cohort study in inflammatory bowel disease and irritable bowel syndrome

et al. 2020

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IntroductionGut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome.Methods and analysisThis 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity.Ethics and disseminationApproval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.Trial registration number:NCT03131414

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“…Although clinical parameters in combination with, for example, C-reactive protein levels, serology, and fecal calprotectin, are used to follow-up on disease activity, there is a great need for biomarker development in IBD especially toward prediction of disease and therapy outcome. 6 Recent advances in genetic prediction of, for example, anti-tumor necrosis factor response and thiopurine-induced myelosuppression based on largescale genome-wide association studies or whole exome sequencing studies show great promise for clinical implementation. 7 An integrated multiomics data-driven framework focused on clearly defined clinical questions provides a great opportunity to identify biomarkers with clinical applicability.…”

Section: Biomarkersmentioning

confidence: 99%

Multiomics Analyses to Deliver the Most Effective Treatment to Every Patient With Inflammatory Bowel Disease

et al. 2018

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Biomarker-guided stratification of autoimmune patients for biologic therapy

Cited by 7 publications

References 68 publications

The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

IMAGINE Network’s Mind And Gut Interactions Cohort (MAGIC) Study: a protocol for a prospective observational multicentre cohort study in inflammatory bowel disease and irritable bowel syndrome

Multiomics Analyses to Deliver the Most Effective Treatment to Every Patient With Inflammatory Bowel Disease

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