TY - JOUR
T1 - Organization of the autoantibody repertoire in healthy newborns and adults revealed by system level informatics of antigen microarray data
AU - Madi, Asaf
AU - Hecht, Inbal
AU - Bransburg-Zabary, Sharron
AU - Merbl, Yifat
AU - Pick, Adi
AU - Zucker-Toledano, Merav
AU - Quintana, Francisco J.
AU - Tauber, Alfred I.
AU - Cohen, Irun R.
AU - Ben-Jacob, Eshel
PY - 2009/8/25
Y1 - 2009/8/25
N2 - 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.
AB - 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.
KW - Immune development
KW - Immune holography
KW - Immune network
KW - Network cliques
UR - http://www.scopus.com/inward/record.url?scp=70149102930&partnerID=8YFLogxK
U2 - 10.1073/pnas.0901528106
DO - 10.1073/pnas.0901528106
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AN - SCOPUS:70149102930
SN - 0027-8424
VL - 106
SP - 14484
EP - 14489
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 34
ER -