title: 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 cliques-subgroups 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.
authors: The Sackler School of Medicine and The Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Asaf
authors: A
authors: Madi
authors: Inbal
authors: I
authors: Hecht
authors: Sharron
authors: S
authors: Bransburg-Zabary
authors: Yifat
authors: Y
authors: Merbl
authors: Adi
authors: A
authors: Pick
authors: Merav
authors: M
authors: Zucker-Toledano
authors: Francisco J
authors: FJ
authors: Quintana
authors: Alfred I
authors: AI
authors: Tauber
authors: Irun R
authors: IR
authors: Cohen
authors: Eshel
authors: E
authors: Ben-Jacob
mesh_terms: D000328:Adult; D000465:Algorithms; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000145:classification / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007136:Immunoglobulins / Q000032:analysis*; D007231:Infant, Newborn; D048088:Informatics / Q000379:methods; D008431:Maternal-Fetal Exchange / Q000276:immunology; D046228:Microarray Analysis / Q000379:methods; D010920:Placenta / Q000276:immunology; D011247:Pregnancy
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins