A step beyond the hygiene hypothesis—immune-mediated classes determined in a population-based study

Abstract

Background Comorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables. Methods LCA was applied to data from the CoLaus|PsyCoLaus study ( N = 4874, age range 35–82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1β, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts. Results LCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men. Conclusions This is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.

The Hygiene Hypothesis and New Perspectives—Current Challenges Meeting an Old Postulate

“…LCA approaches using data from patient studies elucidated that there might be phenotypic asthmatic manifestations that could be explained by the Hygiene Hypothesis while other phenotypes that might have different pathomechanistic origins failed to be covered by this supposition ( 53 ). Among others, this discrepancy led to new approaches in pre-clinical animal-based experimental set-ups as well as investigations based on human data.…”

Hygiene hypothesis: association between hygiene and asthma among preschool children in Lebanon

“…The association between childhood infections, atopic diseases, and unfavorable childhood experiences reveals an immune-mediated system that integrates and even surpasses the hygiene hypothesis. 16…”

The Psychobiology of Bereavement and Health: A Conceptual Review From the Perspective of Social Signal Transduction Theory of Depression

“…In addition, inflammatory activity can negatively affect mental health, and has been found to play a role in the development of anxiety disorders, post-traumatic stress disorder (PTSD), and depression (26). In this context, the cytokines interleukin (IL)-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) have been shown to be both upregulated (17,(28)(29)(30)(31)(32).…”

“…Another pathway by which bereavement may influence health is by affecting genetic and epigenetic pathways. Early life stress exposure has been associated with heightened physiological stress sensitivity as indexed by inflammatory activity and reactivity, as well as with greater immune system dysregulation later in life ( 30 , 47 , 140 – 143 ). In terms of gene expression, stress-induced epigenetic changes can result in altered gene expression ( 38 ).…”