Sanne Hoeks

General Discussion 111 7 THE ADULT IMMUNOLOGICAL WELLNESS PROFILE: HOW TO GET THERE? The Wellness Profile hypothesis proposes that healthy individuals share an immune signature whereas in people with a chronic immune-mediated disease a deviation of this immune signature can be identified – a type of illness profile. 25, 47 According to the standard paradigm, health is a given; health is freedom from pathogenic agents such as bacteria, viruses or malignant cells. 49 The discovery of the DNA genetic code has added mutant or abnormal DNA to the causes of disease. Immune machine learning suggests that immunological wellness is not merely the absence of a specific disease but a particular body state, one that must be learned during early immune repertoire development. 47 This wellness theory suggests that a chronic or recurrent disease might arise from replacement of a healthy reference set of immune body data with an aberrant reference set. Treatment of an auto-immune disease might aim at immune re-education toward a healthy reference profile rather than primarily at suppression of autoreactivity. This concept fits within the window of opportunity as a deviation of the programmed immune development by early-life exposures influences the risk of developing immune- mediated diseases. 25, 50, 51 This proposed window of opportunity further implies that the human immune system is a sensory system for intrinsic and extrinsic environmental factors. It depends on sensory inputs during its development and specific interactions between the developing immune system and the microbes colonizing the intestine, skin, and airways of a newborn child have been suggested as important. 25 Systems-level analyses in humans have shown that environmental influences explain most of the overall variation among healthy individuals 52-55 and that such environmental influences from infections, vaccines, nutrition, and the microbiome exert a cumulative influence over the course of life. 25, 52, 56 Exposome and the microbiome The complexity of environmental exposures over time is termed the exposome. 43, 57 Many of the exposomal conditions and factors operate in a longitudinal fashion over time and have a strong effect on the development of microbial communities at the skin and mucosal sites. 43 It has now been recognized that the major environmental signals driving normal postnatal maturation of immunocompetence in all mammalian species originate from the microflora of the gastrointestinal tract (GIT) 43, 58 and early gut dysbiosis is associated with a perturbation of the stereotypic developmental trajectory. 25 The evolving paradigm is now that colonization of the infant GIT with an appropriate microbiota within crucial developmental time windows is required to optimally drive immune function maturation. 59 Contact with antigens directly after birth is not only pivotal to gain unspecific suppressive regulatory functions that results in tolerance to environmental antigens but