Maternal IgA2 Recognizes Similar Fractions of Colostrum and Fecal Neonatal Microbiota.

Microbiota acquired during labor and through the first days of life contributes to the newborn's immune maturation and development. Mother provides probiotics and prebiotics factors through colostrum and maternal milk to shape the first neonatal microbiota. Previous works have reported that immunoglobulin A (IgA) secreted in colostrum is coating a fraction of maternal microbiota. Thus, to better characterize this IgA-microbiota association, we used flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in human colostrum and neonatal feces. We identified IgA bound bacteria (IgA+) and characterized their diversity and composition shared in colostrum fractions and neonatal fecal bacteria. We found that IgA2 is mainly associated with Bifidobacterium, Pseudomonas, Lactobacillus, and Paracoccus, among other genera shared in colostrum and neonatal fecal samples. We found that metabolic pathways related to epithelial adhesion and carbohydrate consumption are enriched within the IgA2+ fecal microbiota. The association of IgA2 with specific bacteria could be explained because these antibodies recognize common antigens expressed on the surface of these bacterial genera. Our data suggest a preferential targeting of commensal bacteria by IgA2, revealing a possible function of maternal IgA2 in the shaping of the fecal microbial composition in the neonate during the first days of life.

Colostrum IgA1 antibodies recognize antigens from Helicobacter pylori and prevent cytoskeletal changesin human epithelial cells.

Helicobacter pylori is a Gram-negative bacterium found on the luminal surface of the gastric mucosa in at least 50% of the world's human population. The protective effect of breastfeeding against H. pylori infection has been extensively reported; however, the mechanisms behind this protection remain poorly understood. Human IgA from colostrum has reactivity against H. pylori antigens. Despite that IgA1 and IgA2 display structural and functional differences, their reactivity against H. pylori had not been previously determined. We attested titers and reactivity of human colostrum-IgA subclasses by ELISA, immunoblot, and flow cytometry. Colostrum samples from healthy mothers had higher titers of IgA; and IgA1 mostly recognized H. pylori antigens. Moreover, we found a correlation between IgA1 reactivity and their neutralizing effect determined by inhibition of cytoskeletal changes in AGS cells infected with H. pylori. In conclusion, colostrum-IgA reduces H. pylori infection of epithelial gastric cells, suggesting an important role in preventing the bacteria establishment during the first months of life. As a whole, these results suggest that IgA1 from human colostrum provides protection that may help in the development of the mucosal immune system of newborn children.

ANTIGENIC STIMULATION DURING PREGNANCY MODIFIES SPECIFIC IGA1 AND IGA2 SUBCLASSES IN HUMAN COLOSTRUM ACCORDING TO THE CHEMICAL COMPOSITION OF THE ANTIGEN.

BACKGROUND: Several studies have evaluated the effect of infectious diseases and vaccine protocols during pregnancy on maternal milk immunoglobulin (Ig) levels, to understand the protection conferred by lactation on newborns. Colostrum is the primary source of maternal IgA for the newborn. IgA participates in protection mechanisms in the neonate's mucosa. In humans, IgA has two subclasses with differential anatomical distribution among mucosal compartments. Total IgA levels in maternal milk vary after antigen stimulation and have differential affinities in function of the chemical composition of the antigens. We studied the effect of antigenic stimulation during pregnancy on the concentrations of specific IgA1 and IgA2 subclasses in human colostrum. METHODS: We analyzed data from 113 women in Mexico City and compared the amount of IgA subclasses in colostrum against three antigens: two from vaccine protocols (tetanus toxoid and pneumococcal polysaccharides) and lipopolysaccharide, a ubiquitous antigen in the gastrointestinal tract. RESULTS: In agreement with the previous reports, we showed that IgA1 from colostrum mainly recognized protein antigens; in sharp contrast, IgA2 was mostly directed against polysaccharide antigens. These levels increased in women who had previous contacts through vaccination or infections during pregnancy. CONCLUSIONS: Antigen interaction during pregnancy increased the amount of specific IgA subclasses, depending on the chemical composition of the antigen.

Antigenic stimulation during pregnancy modifies specific iga1 and iga2 subclasses in human colostrum according to the chemical composition of the antigen

ABSTRACT Background: Several studies have evaluated the effect of infectious diseases and vaccine protocols during pregnancy on maternal milk immunoglobulin (Ig) levels, to understand the protection conferred by lactation on newborns. Colostrum is the primary source of maternal IgA for the newborn. IgA participates in protection mechanisms in the neonate's mucosa. In humans, IgA has two subclasses with differential anatomical distribution among mucosal compartments. Total IgA levels in maternal milk vary after antigen stimulation and have differential affinities in function of the chemical composition of the antigens. We studied the effect of antigenic stimulation during pregnancy on the concentrations of specific IgA1 and IgA2 subclasses in human colostrum. Methods: We analyzed data from 113 women in Mexico City and compared the amount of IgA subclasses in colostrum against three antigens: two from vaccine protocols (tetanus toxoid and pneumococcal polysaccharides) and lipopolysaccharide, a ubiquitous antigen in the gastrointestinal tract. Results: In agreement with the previous reports, we showed that IgA1 from colostrum mainly recognized protein antigens; in sharp contrast, IgA2 was mostly directed against polysaccharide antigens. These levels increased in women who had previous contacts through vaccination or infections during pregnancy. Conclusions: Antigen interaction during pregnancy increased the amount of specific IgA subclasses, depending on the chemical composition of the antigen.

Infectious episodes during pregnancy, at particular mucosal sites, increase specific IgA1 or IgA2 subtype levels in human colostrum.

BACKGROUND: Colostrum is the primary source of maternal immunoglobulin A (IgA) for the newborn. IgA participates in protection and regulation mechanisms of the immune response at the neonate's mucosa. Several studies have evaluated infectious diseases and vaccine protocols effects during pregnancy on maternal milk IgA levels, with the aim to understand lactation protecting effect on newborn. However, most of their results demonstrated that there were no differences in the total IgA levels. In humans, IgA has two subclasses (IgA1 and IgA2), they have an anatomical distribution among mucosal compartments, their levels vary after antigen stimulation and are also seen to describe differential affinities in colostrum. Although there are differences between IgA subclasses in several compartments, these studies have excluded specific colostrum IgA1 and IgA2 determination. METHODS: We analyzed data from 900 women in Mexico City. With Pearson correlation, we compared the number of infectious episodes during their pregnancy that was associated with mucosal compartments (skin, respiratory and gastrointestinal tracts) and colostrum IgA subclasses. RESULTS: We show a correlation between increased colostrum IgA1 levels and the number of infectious episodes at respiratory tract and the skin. In contrast, infections at the gastrointestinal tract correlated with increased IgA2 amounts. CONCLUSIONS: Infections present during pregnancy at certain mucosal site increase specific IgA subclasses levels in human colostrum. These results will help in understanding infections and immunizations effects on maternal IgA at the mammary gland, and their impact on the development and protection of the newborn.

[Human microbiota association with immunoglobulin A and its participation in immune response]. / La asociación de la microbiota humana con la inmunoglobulina A y su participación en la respuesta inmunológica.

Human microbiota is the aggregate of microorganisms that reside in our body. Its phylogenetic composition is related to the risk for suffering from inflammatory diseases and allergic conditions. Humans interact with a large number and variety of these microorganisms via the skin and mucous membranes. An immune protection mechanism is the production of secretory IgA (SIgA), which recognizes resident pathogenic microorganisms and prevents their interaction with host epithelial cells by means of immune exclusion. Formerly, it was thought that SIgA only function in mucous membranes was to recognize and exclude pathogens, but thanks to the use of massive sequencing techniques for human microbiota phylogenetic characterization, now we know that it can be associated with pathogenic and non-pathogenic microorganisms, an association that is important for functions the microbiota carries out in epithelia, such as regulating the capability of certain microbial species to settle on the skin and mucous membranes, and stimulation and regulation of the immune response and of the risk for the development of inflammatory problems, allergic conditions, autoimmune diseases, and even cancer. Established microbiota determines the type of bacterial species (and probably viral and protozoan species) that reside on the skin and mucous membranes, promoting microbial diversity.

La microbiota humana es el conjunto de microorganismos que residen en nuestro cuerpo. Su composición filogenética está relacionada con el riesgo de padecer enfermedades inflamatorias y cuadros alérgicos. Los humanos interaccionamos con una gran cantidad y variedad de estos microorganismos a través de la piel y las mucosas. Un mecanismo de protección inmunológica es la producción de la IgA secretora (IgAS), que reconoce los microorganismos patógenos residentes y evita su interacción con las células epiteliales del hospedero mediante la exclusión inmunológica. Se creía que la única función de la IgAS en las mucosas era reconocer y excluir a los patógenos, pero gracias a la secuenciación masiva para la caracterización filogenética de la microbiota humana ahora sabemos que puede estar asociada con microorganismos patógenos y no patógenos, asociación importante para las funciones que la microbiota lleva a cabo en los epitelios: regulación de la capacidad de ciertas especies microbianas para establecerse en la piel y en las mucosas, estimulación y regulación de la respuesta inmunológica, del riesgo de desarrollar problemas inflamatorios, cuadros alérgicos, enfermedades autoinmunes e, incluso, cáncer. La microbiota establecida determina las especies bacterianas (y probablemente también virales y de protozoarios) que residen en la piel y en las mucosas, promoviendo la diversidad microbiana.