Dermatologic and Ocular Diseases
Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with the subsequent development of atopy, eczema, or both,☆☆

https://doi.org/10.1067/mai.2002.123535Get rights and content

Abstract

Background: Exposure to various microbial products in early life reduces the risk of atopy. Such exposure induces downregulation of TH2 allergy-biased responses by means of pattern recognition molecules, such as CD14, an LPS receptor. Objective: We sought to determine whether infant and maternal levels of soluble CD14 (sCD14) are associated with the atopic outcomes of infants. Methods: Levels of sCD14 in plasma, amniotic fluid, and breast milk were measured with a specific ELISA in different cohorts. Expression of toll-like receptors in the fetal gut was examined by using RT-PCR. Results: Soluble CD14 levels increased during fetal development and postnatally, attaining adult levels by around 4 months of age, with an overshoot of adult levels from 6 months of age. There was no difference in plasma sCD14 levels at birth of children with a high compared with those with a low risk of development of atopy. Amniotic fluid sCD14 levels at midgestation (16-17 weeks) were significantly lower when the child was subsequently atopic (P < .05). Soluble CD14 levels in breast milk collected 3 months postpartum were significantly lower in children with eczema at 6 months of age, irrespective of whether they were atopic (P = .003). Transcripts for toll-like receptor 4, which would enable transmembrane signaling for LPS/sCD14 complexes, were expressed within fetal gut and skin. Conclusion: Exposure to reduced levels of sCD14 in the fetal and neonatal gastrointestinal tract is associated with the development of atopy, eczema, or both. Thus the exogenous supply of sCD14 might influence immunologic reactivity both locally and systemically in early life and thereby influence disease outcome. (J Allergy Clin Immunol 2002;109:858-66.)

Section snippets

Source of samples

Samples from discrete cohorts were used, and these are summarized in Table I.

. Cohorts used and sources of all samples analyzed in the study

Study number*SamplesAge at clinical assessment†Complete or ongoing
Study 1Serial plasma at birth (cord blood), 6 mo, 1 y, and 5 y of age; high-risk cohort6 mo and 1, 2, 3, 4, and 5 yComplete
Study 2Amniotic fluid at diagnostic amniocentesis (16-18 wk of gestation); not selected on family history of atopy1 yOngoing
Study 3Breast milk at 3 mo postpartum;

RT-PCR

RNA was extracted by using RNase-free DNase treatment with the RNeasy total RNA isolation system, as directed by the manufacturer (Qiagen Ltd). First-strand cDNA synthesis was performed with 0.5 μg of total RNA in a 20-μL reaction by using the Omni-script reverse transcriptase kit (Qiagen Ltd) primed with oligo T17 (AGC, Sigma Genosys), as recommended by the manufacturer.

PCR reactions were performed in a total reaction volume of 25 μL with 1 μL of cDNA in 1× reaction buffer, with 1.5 mmol/L MgCl

Maturation of sCD14 levels

Samples from studies 4 and 5 were used to examine the natural maturation of circulating sCD14 levels. Fetal-neonatal plasma (study 5) sCD14 levels increased significantly with gestational age but remained significantly lower at term than those in adults (Fig 1, A ).

. Maturation of plasma sCD14 levels. Plasma sCD14 was measured by means of specific ELISA in samples collected prenatally (study 5; A ) and postnatally (study 4; B ) and compared with levels in the adult (study 5). *Significantly

Discussion

To study the potential contribution of sCD14 to the development of atopic diseases in infancy, we took advantage of various samples from a number of cohorts collected by our group over the past few years. One of these cohorts (study 1) has completed clinical assessment, whereas the remainder (studies 2, 3, and 4) are ongoing. Differences in the timing of clinical assessment referred to throughout reflect the different ages of the cohort being analyzed. Soluble CD14 was the focus of this study

Acknowledgements

We thank the staff in the Department of Fetal Medicine and in the delivery suite at the Princess Anne Hospital, Southampton, for their assistance in the collection of samples and to the MRC Tissue Bank for fetal tissue. We also thank all the mothers and children who participated in this study.

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    Supported by the National Heart, Lung, and Blood Institute (grant number HL61858); the National Asthma Campaign (UK); the British Lung Foundation; and the Food Standards Agency (grant number T07005).

    ☆☆

    Reprint requests: Catherine A. Jones, PhD, Allergy and Inflammation Sciences, Level G Mailpoint 803, Southampton General Hospital, Southampton, UK, SO16 6YD.

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