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. 2019 Apr 9;17(1):75.
doi: 10.1186/s12916-019-1311-z.

A Step Beyond the Hygiene Hypothesis-Immune-Mediated Classes Determined in a Population-Based Study

Free PMC article

A Step Beyond the Hygiene Hypothesis-Immune-Mediated Classes Determined in a Population-Based Study

Vladeta Ajdacic-Gross et al. BMC Med. .
Free PMC article


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.

Keywords: Biomarkers; Chronic diseases; Hygiene hypothesis; Immune system; Latent class analysis; Mental disorders.

Conflict of interest statement

Authors’ information

The authors of this interdisciplinary study represent epidemiology, immunology, psychiatry, internal medicine, psychosomatic research, pediatric and clinical psychology, methodology.

Ethics approval and consent to participate

The Institutional Ethics Committee of the University of Lausanne approved the CoLaus|PsyCoLaus study. All participants signed a written informed consent form after receiving a detailed description of the goal, procedures and funding of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Fig. 1
Fig. 1
CoLaus|PsyCoLaus sample design
Fig. 2
Fig. 2
Latent class analysis with infectious childhood diseases, atopic diseases, and childhood adversities in the PsyCoLaus study; probabilities of the five-class model, men
Fig. 3
Fig. 3
Latent class analysis with infectious childhood diseases, atopic diseases, and childhood adversities in the PsyCoLaus study; probabilities of the five-class model, women
Fig. 4
Fig. 4
Proportions of latent classes, men; overall and after median split
Fig. 5
Fig. 5
Proportions of latent classes, women; overall and after median split
Fig. 6
Fig. 6
White blood cell counts across latent classes, by sex; means (leukocytes) and proportions (specific white blood cells); data smoothed by square root
Fig. 7
Fig. 7
Mean ranks of inflammatory markers from two assessments, across latent classes, by sex

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