Abstract
MotivationNew antigen microarray technology enables parallel recording of antibody reactivities with hundreds of antigens. Such data affords system level analysis of the immune system's organization using methods and approaches from network theory. Here we measured the reactivity of 290 antigens (for both the IgG and IgM isotypes) of 10 healthy mothers and their term newborns. We constructed antigen correlation networks (or immune networks) whose nodes are the antigens and the edges are the antigen-antigen reactivity correlations, and we also computed their corresponding minimum spanning trees (MST) – maximal information reduced sub-graphs. We quantify the network organization (topology) in terms of the network theory divergence rate measure and rank the antigen importance in the full antigen correlation networks by the eigen-value centrality measure. This analysis makes possible the characterization and comparison of the IgG and IgM immune networks at birth (newborns) and adulthood (mothers) in terms of topology and node importance.ResultsComparison of the immune network topology at birth and adulthood revealed partial conservation of the IgG immune network topology, and significant reorganization of the IgM immune networks. Inspection of the antigen importance revealed some dominant (in terms of high centrality) antigens in the IgG and IgM networks at birth, which retain their importance at adulthood.
Highlights
The recently introduced new antigen microarray chip enables detection in parallel of the patterns of antibodies binding to hundreds of antigens, and so provides a system-level view of the antibody repertoire [1,2,3]
Global view of the combined antigen-reactivity networks Antibodies of the IgM isotype are produced by B cells in the first phase of an antibody immune response, and IgM antibodies have been proposed to regulate the development of IgG autoantibodies [25] and prevent autoimmune diseases [26]
Inspection of these immune trees reveals a higher integration between the IgG and IgM isotypes for the mothers (Figure 2A) compared to the newborns (Figure 2B): for the mothers’ tree, the two isotypes appear on the same branches, but tend to be segregated into different branches in the newborns’ tree. To quantify these differences between the newborn and the maternal merged minimum spanning trees (MST), we measured the topological distances between the different nodes in each of the trees, where the topological distance is measured in terms of the number of edges
Summary
The recently introduced new antigen microarray chip enables detection in parallel of the patterns of antibodies binding to hundreds of antigens, and so provides a system-level view of the antibody repertoire [1,2,3]. We analyzed autoantibody reactivity data of IgM and IgG isotypes present in the sera of 10 healthy mothers at childbirth and in the sera of the cord bloods of their offspring. The antigenantigen correlation matrices revealed that the IgG repertoires of each mother and her offspring were very closely related and distinct for each mother-newborn pair [4]. The IgM repertoires, in contrast, differed markedly between mothers and offspring; each mother manifested a different pattern of IgM reactivities that was distinct from her offspring’s cord IgM repertoire. The IgM reactivities of each of the newborn samples manifested very similar antigen-binding profiles indicating that in utero each developing fetus produced autoantibodies to a similar set of selfmolecules. A subsequent analysis of the data revealed that the reactivity profiles to certain self-molecules were highly correlated as sets of functional antigen-reactivity cliques [4]
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