Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with the subsequent development of atopy, eczema, or both.
BACKGROUND
Exposure to various microbial products in early life reduces the risk of atopy. Such exposure induces downregulation of T(H)2 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.


CONCLUSIONS
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.
Jones
Catherine A
CA
Divisions of Infection, Inflammation and Repair and Human Genetics, School of Medicine, University of Southampton, Southampton, United Kingdom.
Holloway
Judith A
JA
Popplewell
Eleanor J
EJ
Diaper
Norma D
ND
Holloway
John W
JW
Vance
Gillian H s
GH
Warner
Jill A
JA
Warner
John O
JO
D000653:Amniotic Fluid / Q000276:immunology*; D029721:Drosophila Proteins; D004485:Eczema / Q000209:etiology*; D005312:Fetal Blood; D005333:Fetus / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D007223:Infant; D007231:Infant, Newborn; D018950:Lipopolysaccharide Receptors / Q000032:analysis* / Q000097:blood; D008562:Membrane Glycoproteins / Q000235:genetics; D008895:Milk, Human / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D012995:Solubility; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors