Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics

Abstract

Autoimmune diseases are often marked by autoantibodies binding to self antigens. However, many healthy persons also manifest autoantibodies that bind to self antigens, known as natural autoantibodies. In order to characterize natural autoantibodies present at birth, we used an antigen microarray (antigen chip) to analyze informatically (with clustering algorithms and correlation mapping) the natural IgM, IgA, and IgG autoantibody repertoires present in 10 pairs of sera from healthy mothers and the cords of their newborn babies. These autoantibodies were found to bind to 305 different, mostly self, molecules. We report that in utero, humans develop IgM and IgA autoantibodies to relatively uniform sets of self molecules. The global patterns of maternal IgM autoantibodies significantly diverged from those at birth, although certain reactivities remained common to both maternal and cord samples. Because maternal IgG antibodies (unlike IgM and IgA) cross the placenta, maternal and cord IgG autoantibodies showed essentially identical reactivities. We found that some self antigens that bind cord autoantibodies were among the target self antigens associated with autoimmune diseases later in life. Thus, the obviously benign autoimmunity prevalent at birth may provide the basis for the emergence of some autoimmune diseases relatively prevalent later in life.

Figure 1. Correlation coefficient map comparing each sample with each of the other samples.

The 10 cord and 10 maternal samples are shown, and the mean IgG, IgM, and IgA reactivities of the 305 tested antigens were compared to determine correlation. The scale shows the degree of correlation from 0 (black) to 1 (white).

Figure 2. Clustering of cord and maternal IgM and IgA.

Hierarchical clusterings of IgM (A) and IgA (B) reactivities for the maternal and cord samples based on their reactivities to each of the 305 antigens in the array. A color code denoting maternal (blue) and cord (red) samples is shown at the bottom. The color scale shows the relative degree of antibody binding from low (dark blue) to high (dark red).