Organization of the autoantibody repertoire in healthy newborns and adults revealed by system level informatics of antigen microarray data

Abstract

The immune system is essential to body defense and maintenance. Specific antibodies to foreign invaders function in body defense, and it has been suggested that autoantibodies binding to self molecules are important in body maintenance. Recently, the autoantibody repertoires in the bloods of healthy mothers and their newborns were studied using an antigen microarray containing hundreds of self molecules. It was found that the mothers expressed diverse repertoires for both IgG and IgM autoantibodies. Each newborn shares with its mother a similar repertoire of IgG antibodies, which cross the placental but its IgM repertoire is more similar to those of other newborns. Here, we took a system-level approach and analyzed the correlations between autoantibody reactivities of the previous data and extended the study to new data from newborns at birth and a week later, and from healthy young women. For the young women, we found modular organization of both IgG and IgM isotypes into antigen cliquessubgroups of highly correlated antigen reactivities. In contrast, the newborns were found to share a universal congenital IgM profile with no modular organization. Moreover, the IgG autoantibodies of the newborns manifested buds of the mothers' antigen cliques, but they were noticeably less structured. These findings suggest that the natural autoantibody repertoire of humans shows relatively little organization at birth, but, by young adulthood, it becomes sorted out into a modular organization of subgroups (cliques) of correlated antigens. These features revealed by antigen microarrays can be used to define personal states of autoantibody organizational motifs.immune development ͉ immune holography ͉ immune network ͉ network cliques

Tumor-Associated and Disease-Associated Autoantibody Repertoires in Healthy Colostrum and Maternal and Newborn Cord Sera

“…2C and 2D show that individual newborn IgM and IgA repertoires, relative to the scatter of maternal repertoires, were much more tightly packed in repertoire space; thus, the IgM and IgA cord serum isotypes showed a much higher correlation between the repertoires of individual newborns than did the individual IgM and IgA isotypes of their mothers. In other words, the IgM and IgA Abs produced by developing babies in utero manifest relatively similar global repertoires (13,14). Fig.…”

“…We used some of the same Ags as in the previous studies of healthy autoimmune repertoires (13,14); these included proteins, synthetic peptides from the sequences of key proteins, nucleotides, phospholipids, and other self and nonself molecules. See Supplemental Table I for the full list.…”

“…1 for additional details). For dimensional reduction we used the Principal Component Analysis (PCA) algorithm (18) on the normalized Pearson correlation matrices, as previously described (13). Note that subjects manifesting relatively high normalized correlations are closely located in the three-dimensional space.…”

“…The blood samples were allowed to clot at room temperature. After centrifugation, sera were collected and stored at 220˚C (13,14).…”

“…The women were all healthy, and their newborns' gestational age ranged from week 27 to 41. The soluble fraction of the milk was separated from the fat by centrifugation, collected, and stored at 220˚C (13,14).…”