The Breast Milk Immunoglobulinome

Abstract

Breast milk components contribute to the infant's immune development and protection, and among other immune factors, immunoglobulins (Igs) are the most studied. The presence of IgA in milk has been known for a long time; however, less information is available about the presence of other Igs such as IgM, IgG, and their subtypes (IgG1, IgG2, IgG3, and IgG4) or even IgE or IgD. The total Ig concentration and profile will change during the course of lactation; however, there is a great variability among studies due to several variables that limit establishing a clear pattern. In this context, the aim of this review was firstly to shed light on the Ig concentration in breast milk based on scientific evidence and secondly to study the main factors contributing to such variability. A search strategy provided only 75 studies with the prespecified eligibility criteria. The concentrations and proportions found have been established based on the intrinsic factors of the study-such as the sampling time and quantification technique-as well as participant-dependent factors, such as lifestyle and environment. All these factors contribute to the variability of the immunoglobulinome described in the literature and should be carefully addressed for further well-designed studies and data interpretation.

Keywords: IgA; breast milk; immunoglobulin; immunoglobulinome.

Figure 1

The secretion of Igs in human milk. Schematic figure of the local production pathway of Igs (involving the B cell homing to the mammary gland and participation of the secretory component) and the systemic production pathway (involving the monomeric Igs plasma filtration from plasma).

Figure 2

Diagram of the different phases of the search strategy. The flow figure shows the number of articles obtained after the identification and screening steps and those finally used for the review after the eligibility and final inclusion steps. Other sources correspond to the articles related to the topic found in the bibliography of the revised documents.

Figure 3

Evolution of the number of studies quantifying Ig types (A) and IgG subtypes (B) over the years.

Figure 4

Evolution of the techniques used to measure immunoglobulin levels over the years. EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay.

Figure 5

IgA (A), IgM (B), and IgG (C) levels presented in the literature throughout the different phases of breastfeeding. The mean values from each Ig were calculated and shown in the graph using the values provided in the articles for a particular group, independently of the number of samples they are derived from. Figure A takes into account both the determinations obtained from IgA studies and those that claim to measure SIgA specifically.

Figure 6

Global proportions from the immunoglobulin concentrations found in the literature. Proportions of Ig classes are expressed in each stage of lactation: colostrum (A), transition (B), and mature (C) milk. IgG subclass proportions were expressed in colostrum (D) and mature milk (E), as there are no current data for transition milk in this regard.

Figure 7

Prenatal and postnatal factors influencing breast milk immunoglobulinome. The factors are displayed from the highest to lowest level of evidence.