Quantification of Female Chimeric Cells in the Tonsils of Male Children and Their Determinants

Abstract

The factors influencing mother-to-child cell trafficking and persistence over children's lives have yet to be established. The quantification of maternal microchimerism was previously reported through HLA-based approaches, which introduced bias regarding the tolerogenic environment. We aimed to identify cells of maternal origin irrespective of the HLA repertoire and to ascertain the determinants of microchimeric cells. This case-control study enrolled 40 male infants attending pediatric surgery from January 2022 to October 2022. Female cells were quantified in infants' tonsil tissue by using cytogenetic fluorescent in situ hybridization (FISH) coupled with optimized automated microscopy. Out of the 40 infants, half (47.4%) had been breastfed for more than one month, a quarter for less a month, and 10 children (26.3%) were never breastfed. XX cells were observed in male tonsils in two-thirds of participants at a median density of 5 cells per 100,000 cells. In univariate analyses, child age was negatively associated with a high female cell density. In exploratory multivariate analyses, previous breastfeeding is a likely determinant of the persistence of these cells in the host, as well as the rank among siblings. Part of the benefit of breastmilk for child health may therefore be driven by breastfeeding-related microchimerism.

Keywords: FISH; automated microscopy scanning; breastfeeding; cell trafficking; microchimerism; tonsil.

Figure 1

Examples of interphase nuclei after probe hybridization and classification. The same patient presented male cells (A), but also female cells (B,C). Red spot = Y chromosome, green spot = X chromosome and cyan spot = chromosome 18.

Figure 2

Fitted values and 95% CI from the final multivariate model for the interaction between having ever been breastfed during early infancy and child age, independently of BMI, sibling rank, and the duration of breastfeeding.