Selecting and interpreting markers of immunomodulation in nutrition studies. Jalil Benyacoub, PhD Nutrition & Immunity task force

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1 Selecting and interpreting markers of immunomodulation in nutrition studies Jalil Benyacoub, PhD Nutrition & Immunity task force

2 Outlines Overview on the immune system, immune functions and Nutrition Summary of ILSI Nutrition & Immunity task force past activities Overview of recent activity: Immunomodulation by nutrition in the general population Perspective: New activity 2

3 Understanding the complexity of the immune system and its role in maintaining health Immune balance is important for health B CD4 Thymus Adenoids Tonsils Specific humoral response CD4 Spleen Thoracic duct Peyer s patches Infection T CD8 Specific cellular response: Cytotoxicity Appendix Lymph nodes Tissue lymphatics Bone marrow Inflammatory diseases Protection against infections Atopy/Allergy From 3

4 Understanding the impact of nutrition on immune functions and its consequences on health Nutrition Nutrition Immune maturation mune orders Skin Alzheimers Immunomodulation (markers Inflammation & immune functions) Inflammatory Bowel Disease Allergy Cancer Obesity Metabolic Disorders Cardio Vascular Disease Ageing? Joint inflammation Arthritis? Health relevance Maintenance of optimal protection Prevention of infections Prevention/management of allergies Inflammation-associated diseases Ageing-related Immune decline (low grade inflammation) 4

5 Nutrition and Immunity in Man Concise Monograph 1 st edition published in 1999, 2 nd edition published 2011 The update includes new information on pro- and prebiotics, fatty acids and vitamins reduction of disease risk functional foods and health claims related to the immune system The text of each Concise Monograph is peer-reviewed by academic scientists of high standing. 5

6 Immune markers for nutritional intervention In vivo Ex vivo innate immune function Systemic immune markers Response to vaccination DTH response (skin test) Phagocyte function Killer cell activity Vaccine-specific serum antibodies Local response to Ag application Biological relevance Feasibility Usefulness of marker High High Phagocytosis + ++ Low Oxidative burst + ++ Medium NK cell cytolytic function + ++ Medium Ex vivo adaptive immune function Basal markers Lymphocyte function Circulating factors Circulating leucocytes Proliferation ++ + Medium Cytokine production ++ + Medium Immunoglobulins + ++ Low Acute-phase protein (CRP) Cytokines and cytokines receptors Total blood cell count, lymphocytes subsets + ++ Low - + Low + ++ Low In vivo Basal markers Mucosal immune markers Response to vaccination Secreted factors Vaccine-specific antibodies in saliva or feces Feasibility Usefulness of marker + High Immunoglobulins (IgA) + High Calprotectin + Low (Adapted from Albers et al., 2005 Passclaim) No single marker is sufficient to predict the outcome of an immune function for a particular health condition but series of markers should be considered collectively

7 Immune markers in inflammatory situations: Impact of Nutrition Inflammation Acute inflammation is a normal physiological response crucial for maintaining homeostatic control, but when it becomes chronic, inflammation contributes to the pathophysiology of a range of diseases. Isolated markers cannot be used to distinguish acute or chronic inflammatory processes. Inflammatory responsiveness or resilience to challenges may provide a more sensitive and meaningful indication of inflammatory state in the general population than the assessment of markers during the steady state. 7

8 Selecting and interpreting markers of Immunomodulation in nutrition studies Joint activity: Expert Group commissioned by the Task Forces Probiotics and Nutrition and Immunity Questions: What are relevant immune markers to study during an intervention, focus on infections, allergies & low grade inflammation? Are there reference values existing for these markers? How to interpret their modulation following a dietary intervention? Application to any kind of food ingredient, not only probiotics 8

9 Experts review: Stepwise approach towards guidance for future nutrition studies Evaluation of immune functions & paradigm influencing immunity (nutrition, stress, ) Description & selection of immune markers (selection criteria: technical feasibility, sensitivity functionality and clinical relevance), scoring (prioritization) and clustering Define scenarios of changes reflecting the impact of nutrition and set-up a flow chart to aid future design and interpretation of studies assessing immunomodulation by nutrition Draft review manuscript includes recommendations for markers to include in future studies and/or novel markers to develop/validate Workshop, April 2012 in Nice-Fr with >35 European experts (gastroenterology, pediatrics, immunology, nutrition, clinical pathology, exercise physiology, microbiology ) to review, refine and endorse the manuscript Publication Albers et al. BJN,

10 Scenarios for the modulation of immune markers relative to the reference range value of biomarker(s) upper reference value reference range of less favorable (sub)population reference range of generally healthy population lower reference value reference range of less favorable (sub)population time 10

11 Framework for Interpretation 12

12 Project achievement & Communication ISAPP 2012, Cork, Ireland: Late Breaking News session, oral presentation by Dr. P. Phothirath and Pr. Seppo Salminen 6 th International Immunonutrition Workshop 2012, Mallorca, Spain: Plenary Session, oral presentation by Dr. Ruud Albers ILSI Europe 2014 Annual Symposium, oral presentation by Dr. Jalil Benyacoub Immunonutrition Workshop 2014, Italy: Prof. Philip Calder 13

13 value of biomarker(s) Perspective upper reference value reference range of less favorable (sub)population lower reference value reference range of generally healthy population reference range of less favorable (sub)population New activity: Health Relevance of the Modification of Low-grade Inflammation in Ageing: Causes, Effects and Health & Wellbeing Consequences time Health relevance WHY? Biomarkers of inflammation WHAT? LGI Difference to symptomatic inflammation? Dietary modification HOW? 14

14 Thank you for your attention!