IgA Antibodies, TGF-β1 and -β2, and Soluble CD14 in the Colostrum and Development of Atopy by Age 4

Abstract

Specific defense factors in breast milk together with length of breast-feeding and genetic predisposition may modulate the development of allergy. We studied whether IgA, soluble CD14 (sCD14), or transforming growth factor (TGF)-␤ in colostrum could affect the development of atopy in children up to age 4. From a cohort of 4676, we selected four groups of children with either long or short exclusive breast-feeding (Ͼ3.5 or Ͻ0.5 mo); these groups further differed in the presence or absence of atopic heredity. In colostrum from mothers, we measured total IgA, IgA antibodies to cow's milk (CM) and casein, sCD14, and TGF-␤1 and -␤2. The children were divided into three groups: those with no atopic symptoms or IgE, those with allergic symptoms, and those with both outcomes. Mothers of infants later showing atopic symptoms or, in addition, having IgE sensitization (verified atopy) had a lower concentration of IgA casein antibodies in their colostrum than did mothers of infants with no indication of atopy at age 4. Low concentration of IgA casein antibodies was a significant risk for verified atopy. sCD14 levels were lower in colostrum of mothers with infants developing atopic symptoms and IgE sensitization than of those of infants with no atopy. Specific IgA antibodies to CM antigens and sCD14 in colostrum significantly associated with the appearance of both symptomatic and verified atopy by age 4. Interaction between early infant feeding and subsequent development of allergies has been debated for decades (1-5). Human breast milk contains antibodies to antigens the mother has come into contact with, particularly against food antigens and enteral microbes (6 -10). These antibodies, together with a small amount of food antigens in the milk, may direct the immune response of the infant to develop tolerance or hypersensitivity to those antigens. Breast milk also contains a number of nonspecific anti-infectious substances such as iron-binding lactoferrin, bacteriocidic lysozyme, and the oligosaccharides inhibiting microbial attachment to epithelial cells. It therefore effectively reduces infections of the newborn infant and has an impact on infants' indigenous bacterial flora (8 -10). Human milk, furthermore, contains a number of cytokines (11-16) and other immunomodulatory (17) agents as well as living cells (18), which in the immature intestine of the newborn may modulate the development of local immune responses.We recently showed that the effect of breast-feeding on the appearance of allergic diseases at age 4 y depended on heredity: if the infant has the genetic component for allergy, long breast-feeding seems to protect against allergies; if the heredity is negative, long breast-feeding promotes emergence of allergies (5). Because of such interactions and the fact that maternal heredity has a stronger impact on the appearance of allergies than does paternal allergy (19), breast milk of mothers with allergy has been speculated to differ from that of nonallergic mothers and, in fact, some differences have emerged (20,2...

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“…In partial contrast to our findings, infants with postweaning onset allergic disease received colostrum with higher TGF-␤2 levels than infants with preweaning onset of disease (16). However, this observation is still controversial (15,18,20). That children with transient when compared with persistent sensitization during infancy more often received colostrum with detectable IL-10 may be related to the IgE inhibitory effects of this cytokine (26).…”

“…The controversial results regarding the role of breast-feeding for prevention of allergy development have been suggested to be partly because of differences in breast milk composition (12). For instance, high levels of breast milk IgA (13)(14)(15) and TGF-␤ (16,17) have been suggested to affect the allergy development in the child, although this is still controversial (15,18 -20).…”

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“…52 However, in a birth cohort study, concentrations of either TGF-␤1 or TGF-␤2 in colostrum were not associated with the risk of atopic sensitization or allergic disease by the age of 4 years. 26 This discrepancy may be explained by constitutional differences in the risk of developing atopic disease even though atopic heredity was taken into account in subgroup analyses in the latter study.…”

“…23 Soluble (s)CD14 is found in substantial quantities in breastmilk, 24 and there are epidemiological data suggesting an inverse relationship between breastmilk sCD14 concentrations and the risk of developing atopic disease. 25,26 LeBouder et al 27 have reported that breastmilk modulates innate immune responses to bacterial antigens in human intestinal epithelial cells in vitro. This immunomodulation was demonstrated to be partially dependent on sCD14 in breastmilk.…”

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“…O CD14 solúvel está presente em altas concentrações no leite materno e tem importante papel na indução da resposta de linfócitos T auxiliares a bactérias, podendo também proteger contra o desenvolvimento de alergias 55 . O alto nível de proteína eosinofílica catiônica também proporciona essa proteção.…”