IgGs from Human Milk Hydrolyze microRNAs

Abstract

Mother’s milk provides breast-fed infants with various nutrients, including peptides, proteins, DNA, RNA, antibodies, and other bioactive components promoting neonatal growth and protecting infants from viral and bacterial infection. The functions of many human milk components regarding the nutrition and protection of newborns may be very different compared to those of various biological fluids of healthy adults. For example, human milk contains catalytic antibodies (abzymes) with protein, lipid, and oligosaccharide kinase activities, which are absent in the biological fluids of healthy people and autoimmune patients. Obviously, the nutrition of infants with fresh breast milk is a special phenomenon having a very specific and important role. Here, we have shown that mother’s milk IgGs effectively split homo-(pN)23, and four miRNAs: miR-137, miR-219a-5p, miR-219-2-3p, and miR-9-5p. It was shown that ribonuclease activity is a unique property of milk IgGs. On average, individual IgGs hydrolyze (pA)23, (pU)23, and (pC)23 nonspecifically and with comparable efficiency, whereas the hydrolysis of four miRNAs is predominately site-specific. The specific sites of the hydrolysis of four miRNAs by IgGs from the blood of schizophrenic (SCZ) patients and secretory immunoglobulins A (sIgAs) from human milk were found earlier. The sites of the hydrolysis of four miRNAs by milk IgGs and sIgA-abzymes are almost the same, but are significantly different in comparison with those for SCZ IgGs. In addition, in contrast to the SCZ IgGs, milk IgGs and sIgAs efficiently hydrolyzed miRNAs in the duplex regions formed by their terminal sequences.

Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States

“…IgG and sIgA hydrolyzing DNA [ 59 , 148 , 151 ], RNA [ 148 , 151 ], oligonucleotides [ 148 , 150 , 151 ] and microRNA [ 157 , 158 ] were found in human milk. The presence of abzymes hydrolyzing β-casein [ 152 ] and polysaccharides [ 96 , 149 ] are also shown in the milk of healthy women.…”

“…Colonic infusion of RNase A decreased gut motility but increased bone mass; thus, Piezo1 ultimately regulates the gut peristalsis and bone homeostasis [ 171 ]. Considering our data that human milk sIgA and IgG hydrolyze RNA and microRNA [ 148 , 150 , 151 , 157 , 158 ], it can be assumed that these immunoglobulins are involved in the regulation of peristalsis and bone metabolism in newborns through the hydrolysis of fecal single-stranded RNA. In general, human milk abzymes may play an important role in protecting the newborns from different pathogens and gut homeostasis regulation.…”

MicroRNAs of Milk in Cells, Plasma, and Lipid Fractions of Human Milk, and Abzymes Catalyzing Their Hydrolysis

“…It was shown that IgGs and sIgAs from the sera and milk of lactating mothers have several different catalytic activities ([ 12 , 13 , 14 , 15 , 16 , 17 ] and references therein). Methods of purification and characterization, including electrophoretic homogeneity of the IgG (150 kDa, H 2 L 2 : two light (L) and two heavy (H) chains) and sIgA (340 kDa, (H 2 L 2 ) 2 SJ: four light and four heavy chains, secretory (S) and join (J) components) preparations used in this study, were described in [ 73 , 74 ]. In addition, the relative activities (RAs) of seven individual IgGs and sIgAs from the milk of healthy lactating mothers in hydrolyzing four miRNAs (miR-9-5p, miR-137, miR-219-2-3p, and miR-219a-5p) were characterized.…”

“…In addition, the relative activities (RAs) of seven individual IgGs and sIgAs from the milk of healthy lactating mothers in hydrolyzing four miRNAs (miR-9-5p, miR-137, miR-219-2-3p, and miR-219a-5p) were characterized. Moreover, it was shown that the IgG and sIgA preparations used in this study do not contain impurities of canonical RNases [ 73 , 74 ]. In this study, we first analyzed the RAs of the same IgGs and sIgAs in the cleavage of five microRNAs: miR-148a-3p, miR-200c-3p, miR-378a-3p, miR-146b-5p, and let-7f-5p.…”

“…As noted above, human milk contains many different microRNAs, including these four microRNAs. It has recently been shown that sIgAs and IgGs of human milk effectively hydrolyze four microRNAs that are characteristic of immune diseases: miR-9-5p, miR-219-2-3p, miR-137, and miR-219a-5p [ 73 , 74 ]. However, these four microRNAs are more typical for patients with various ADs.…”