Tumor-associated and disease-associated autoantibody repertoires in healthy colostrum and maternal and newborn cord sera.
In this work, we studied autoantibody repertoires and Ig isotypes in 71 mothers and their 104 healthy newborns (including twins and triplets delivered term or premature). Newborns receive maternal IgG Abs via the placenta before birth, but developing infants must produce their own IgM and IgA Abs. We used an Ag microarray analysis to detect binding to a selection of 295 self-Ags, compared with 27 standard foreign Ags. The magnitude of binding to specific self-Ags was found to be not less than that to the foreign Ags. As expected, each newborn shared with its mother a similar IgG repertoire-manifest as early as the 24th week of gestation. IgM and IgA autoantibody repertoires in cord sera were highly correlated among the newborns and differed from their mothers' repertoires; the latter differed in sera and milk. The autoantibodies bound to self-Ags known to be associated with tumors and to autoimmune diseases. Thus, autoantibody repertoires in healthy humans--the immunological homunculus--arise congenitally, differ in maternal milk and sera, and mark the potential of the immune system to attack tumors, beneficially, or healthy tissues, harmfully; regulation of the tissue site, the dynamics, and the response phenotype of homuncular autoimmunity very likely affects health.
Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel; School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv, Israel; Department of Neonatology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, 5262100 Ramat Gan, Israel;
Asaf
A
Madi
Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel; School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv, Israel;
Sharron
S
Bransburg-Zabary
Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel; Department of Neonatology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, 5262100 Ramat Gan, Israel;
Ayala
A
Maayan-Metzger
School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv, Israel;
Gittit
G
Dar
School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv, Israel; Center for Theoretical Biological Physics, Rice University, Houston, TX 77005; and.
Eshel
E
Ben-Jacob
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel irun.cohen@weizmann.ac.il.
Irun R
IR
Cohen
D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D003126:Colostrum / Q000276:immunology*; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000097:blood* / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007231:Infant, Newborn; D008895:Milk, Human / Q000276:immunology; D009369:Neoplasms / Q000276:immunology
D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M