Elsevier

Clinical Immunology

Volume 152, Issues 1–2, May–June 2014, Pages 68-76
Clinical Immunology

The LINA cohort: Cord blood eosinophil/basophil progenitors predict respiratory outcomes in early infancy

https://doi.org/10.1016/j.clim.2014.02.013Get rights and content

Highlights

  • Predictive value of eosinophil/basophil (Eo/B) progenitor numbers at birth was studied.

  • Higher numbers of cord blood Eo/B progenitor cells predict respiratory outcomes later in life.

  • Tobacco smoke related benzene exposure supports the activation of these progenitors.

  • A Th2 immune status at birth further contributes to higher cord blood Eo/B numbers.

Abstract

Rationale

Cord blood eosinophil/basophil progenitor cells (Eo/B) of high risk infants have been shown to predict respiratory illnesses in infancy. Here we investigated this association in a population-based cohort. Furthermore, we analysed whether newborns Th1/Th2 balance and prenatal environmental exposure impact Eo/B recruitment.

Methods

In a sub-cohort of the LINA study cord blood mononuclear cells were used for methylcellulose assays to assess Eo/B differentiation. Questionnaires were recorded during pregnancy and annually thereafter. Volatile organic compounds were measured during pregnancy and cord blood cytokines after ex vivo stimulation.

Results

Cord blood IL-4 and IL-13 positively correlated with Eo/B. Tobacco smoke related benzene was also positively associated with Eo/B. Enhanced Eo/B numbers increased the risk for wheezing within the first 24 months.

Conclusions

The association between cord blood Eo/B and respiratory illnesses is not restricted to high-risk children. Prenatal environmental exposure and a Th2 milieu at birth contribute to Eo/B recruitment.

Introduction

Pre- and early postnatal programming affects the structure and function of the fetal lung. A variety of immune parameters have been found to be involved in lung inflammation and to be affected by the intrauterine environment or environmental exposure during pregnancy. Thus, the immune status at the time of birth might be suitable to identify children at risk to develop respiratory diseases later in life. It has been shown for example that cord blood IL-8 was associated with the risk for wheeze in one year old children [1] or that the Th1/Th2 milieu at the time of birth is related to later asthma [2].

A cell population which is also discussed to predict respiratory and allergic outcomes are eosinophil/basophil progenitor cells in cord blood. It has been shown that there is a deficient maturation of cord blood eosinophil/basophil progenitors caused by a decreased expression of hemopoietic cytokine receptors in a selected group of newborns at risk of atopy [3]. It was also shown that in high risk infants cord blood hematopoietic progenitor cells predict the development of acute respiratory illnesses [4] or recurrent wheeze [5] during the first 12 months. However, it is still not clear, if the predictive value of these cord blood eosinophil/basophil progenitors in terms of respiratory outcomes is only restricted to high risk infants or might also be seen in a general study population. If so, that aspect might even better qualify these cells as a potential neonatal marker for later disease.

There is also literature showing that cord blood progenitors of high risk newborns are sensitive to lifestyle intrauterine modifications, such as n  3 fatty acid supplementation during pregnancy, which leads to an altered infant cord blood hematopoietic progenitor phenotype [5]. However, less is known whether – next to nutritional aspects – environmental triggers to which the newborn is indirectly exposed to in utero also impact on cord blood progenitor cell development. We showed in an earlier study that the direct exposure to tobacco smoke or tobacco smoke related volatile organic compounds (VOC) correlated with Eo/B progenitors in 1 year old children [6].

The aim of the present study was to investigate the association between cord blood Eo/B progenitors and respiratory outcomes in a general study population. We furthermore analysed whether environmental chemicals, such as tobacco smoke-related VOC alter cord blood Eo/B progenitor cell recruitment and whether associations between cord blood Eo/B progenitor cells and other immune parameters exist.

Section snippets

Study design and sample collection

The LINA cohort study (Lifestyle and environmental factors and their Influence on Newborns Allergy risk) recruited 629 mother–child-pairs between May 2006 and December 2008 in Leipzig, Germany, to investigate how environmental factors in the pre- and postnatal period influence immune system development and resulting disease risks [7], [8]. Mothers suffering from immune or infectious diseases during pregnancy were excluded from the study.

606 mother–child-pairs participated in the one year, 546

Study characteristics

General characteristics of the study participants (birth weight, maternal age at delivery, gender of the child, siblings, FHA, family history of asthma, parental education, keeping of a cat, mould in the dwelling as well as the exposure to ETS during pregnancy) are shown in Table 1. There were no differences between the analysed sub-cohort (n = 40) and the total LINA cohort (n = 629).

The prevalence of respiratory outcomes within the first 24 months is shown in Table 2. As well, no differences were

Discussion

In this study we were able to show that cord blood Eo/B progenitor cells correlate with infant's later respiratory outcomes within the first 24 months in a general study population. Further, we could show that the neonatal Th2 milieu is associated with the progenitor cell differentiation. The fact that maternal exposure to tobacco smoke during pregnancy was associated with the number of cord blood Eo/B progenitor cells, gives further evidence for a prenatal programming of the immune system with

Conclusion

In summary, in this study we could demonstrate the association between cord blood Eo/B progenitors and respiratory outcomes like wheezing or bronchitis within the first 24 months in a general study population. This aspect is particularly important if the potential predictive value of this cell population for respiratory outcomes is considered to be used in newborns or early infants. Furthermore, we suggest that a Th2 milieu at birth as well as exposure to environmental pollutants during

Sources of funding

The LINA study was financed by Helmholtz institutional funding (Helmholtz Centre for Environmental Research — UFZ). The German Academic Exchange Service (DAAD) and AllerGen NCE Inc. supported the exchange of the postdoctoral fellow for establishment and validation of the Eo/B progenitor assay.

Conflict of interest

None of the authors has any potential financial conflict of interest related to this manuscript. Dr. Denburg reports that he is the CEO and Scientific Director of AllerGen NCE.

Acknowledgments

We thank all LINA families for participation in the study, Anne Hain for her technical and Melanie Nowak for her excellent study organisation assistance.

References (26)

  • D. Hinz et al.

    Reduced maternal regulatory T cell numbers and increased T helper type 2 cytokine production are associated with elevated levels of immunoglobulin E in cord blood

    Clin. Exp. Allergy

    (2010)
  • I. Lehmann et al.

    The influence of maternal exposure to volatile organic compounds on the cytokine secretion profile of neonatal T cells

    Environ. Toxicol.

    (2002)
  • G. Herberth et al.

    Maternal immune status in pregnancy is related to offspring's immune responses and atopy risk

    Allergy

    (2011)
  • Cited by (0)

    View full text