Tumor-Associated and Disease-Associated Autoantibody Repertoires in Healthy Colostrum and Maternal and Newborn Cord Sera

Abstract

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.

Individual and stable autoantibody repertoires in healthy individuals

“…There are reports of pre-symptomatic patients displaying serum autoantibodies up to 20 years prior onset of an autoimmune disease, for example, anti-TRIM21 reactivity related to Sj€ ogren syndrome [17] and anti-citrullinated-peptide antibodies (ACPA) related to rheumatoid arthritis [18]. Several studies have shown that healthy individuals have detectable levels of serum autoantibodies which suggests that autoantibody positivity is not necessarily disease associated [19][20][21][22][23][24][25][26][27][28][29]. It remains to be seen if any of the individuals we have investigated herein develop autoimmune diseases.…”

Maternal myasthenia gravis represents a risk for the child through autoantibody transfer, immunosuppressive therapy and genetic influence

“…The IgG content in breast milk is similar during the first week after birth and later in the lactating period. Only a small proportion of the milk antibodies are absorbed from the gut and into the baby's circulation . Being breastfed reduces the risk for many autoimmune diseases , especially desirable for children of MG mothers who have already a genetic predisposition.…”

Antigen-Microarray Profiling of Antibodies in SLE: A Personal View ofTranslation from Basic Science to the Clinic

“…The initial study of maternal-cord autoantibodies was expanded recently to a study of 71 mothers and their 104 newborns (including twins and triplets); we also studied antibody reactivities detectible in maternal colostrum [22]. The findings reported in the initial, small study were confirmed in this much larger set of subjects.…”