Eosinophil Cationic Protein in Human Milk Is Associated with Development of Cow's Milk Allergy and Atopic Eczema in Breast-fed Infants

Abstract

The precise role of leukocytes and mediators in human milk is still unresolved. Eosinophils are uncommonly detected in human milk and their presence has previously been associated with maternal atopy and development of cow's milk allergy (CMA) in the breast-fed infant. The purpose of this study was to examine the levels of eosinophil cationic protein (ECP) in human milk and to compare the levels with development of allergic diseases in breast-fed infants. Altogether 94 breast-feeding mothers (58 atopic, 36 nonatopic) with their babies were prospectively followed from birth for development of CMA or atopic dermatitis. Colostrum and mature milk samples (at 3 mo of lactation), together with mother's peripheral blood samples, were collected. Milk and blood leukocyte content was evaluated with a light microscope. ECP concentration in human milk was measured by commercial UniCAP method. By the end of a 2-y follow-up, 51 mothers had an infant with CMA, 24 had an infant with atopic dermatitis, and 19 had a healthy infant. ECP concentration in milk was under the detection limit (2 g/L) in all the mothers with a healthy infant, whereas detectable levels were found in 27% of mothers with a CMA infant and in 42% of those with a baby with atopic dermatitis. Measurable ECP in milk was detected in 26% of the atopic and 25% of the nonatopic mothers. Presence of ECP in human milk is associated with development of CMA and atopic dermatitis in the breast-fed infant, but has no direct association with the maternal atopy. Human breast milk provides nutrients and multiple immunologic factors, like secretory IgA, to the breast-fed infant (1). It is known to be an important immunologic support system extending from the mother to her infant during the first months of life. The precise role of leukocytes in human milk is still unknown. In animal studies, milk leukocytes have been shown to pass through the gastrointestinal mucosa of a suckling newborn (2-5). They produce cytokines and mediators, which may be released throughout the gastrointestinal tract (6). In our previous studies, we have found that macrophage is the predominant leukocyte in milk of mothers with a healthy baby, whereas in the mothers with a CMA infant, neutrophils and eosinophils are found in excess (7). We have also shown that decreased function of macrophages is likewise associated with development of CMA in breast-fed infants (8), suggesting that defective immunologic support from mother's milk may interfere with normal development of oral tolerance to food proteins.Eosinophils are mainly tissue-dwelling cells. The bloodtissue ratio of eosinophils has been estimated to be 1:100 (9) Eosinophils are presumably involved in normal immune defense as well as in specific morbid processes including parasitic infections and hypersensitivity reactions (9, 10). Eosinophil granules contain cationic proteins, which have been demonstrated in vivo and in vitro to be tissue-destructive (9). Detection of eosinophil-derived granular proteins reflects earlier degranulation of eosinoph...

Expression of intercellular adhesion molecules on circulating lymphocytes in relation to different manifestations of cow's milk allergy

“…Moreover, Altman et al [30] have demonstrated that eosinophil granule products caused significant up‐regulation of ICAM‐1 on human nasal epithelial cells in vitro . We have previously found increased levels of eosinophil cationic protein (ECP) in the milk of mothers with food‐allergic infants [31]. These increased numbers of neutrophils found in mother's milk might hypothetically serve as storage of ECP because it is reported that ECP is actively taken up by neutrophils and stored in the granules of these cells [32].…”

Immune factors in breast milk related to infant milk allergy are independent of maternal atopy

“…4 All available samples were assessed from 39 mothers of non-CMA infants and 35 mothers of CMA infants, verified by oral food challenges 6 performed at median 5.5 months of age (IQR, 3.1–7.7 months). Clinical characteristics are shown in Table E1.…”

“…Logistic univariate regression was then used to assess the influence of multiple immunologic factors in human milk on CMA onset, including milk immune markers, leukocytes, eosinophilic cationic protein (ECP), and the levels of β-lactoglobulin (BLG)- and casein-specific IgA, which have been previously reported in this cohort. 4–6 After adjusting for maternal covariates, including atopic diseases, age and duration of lactation, the levels of IL-1β (p=0.001), IL-10 (p=0.04) and BLG-specific IgA (p=0.005) were lower in the milk of mothers with a CMA infant than in those with a non-CMA infant and there was a trend for lower IL-6 (p=0.07, Table EIII). …”

The role of breast-feeding in the development of allergies and asthma

“…11 Higher levels of eosinophil cationic protein in breast milk have been associated with a higher incidence of cow's milk allergy and atopic dermatitis in infant recipients. 12 It is unclear how these disparate mechanisms of immunomodulation express themselves in infant mother pairs or whether one will be able to predict, on a case by case basis, how breast milk will effect the development of allergies in a given child. Perhaps an understanding of genetic factors may allow for better predictability in the future.…”