Search for Maternal Microchimerism in Swollen Portal Lymph Nodes of Infants With Biliary Atresia.

Upon operation of infants with non-syndromatic biliary atresia (BA, commonest form), surgeons almost invariably note the prominent finding of multiple swollen lymph nodes of up to 2 cm in size in the porta hepatis and the small bowel mesentery where they may constitute grape like complexes. Same-age infants laparotomized for other pathology commonly do not present such nodes.

Biliary atresia is a disease of the newborn which is fatal when left untreated. Histologically it corresponds to a degeneration of intra- und extra hepatic bile ducts within a in part specific inflammatory infiltrate and progressive cirrhosis.

The etiology of this rare but constant disease (1:8-1:15.000) is unknown. Currently in BA etiology research two main avenues are pursued:

1. Virally induced perinatal (auto)immune processes are suspected. An experimental form of BA can be provoked by infecting murine mothers with dsRNA-viruses e.g. Rhesus-rotaviruses or Reo-viruses while in mice, vaccination of mothers has prevented experimental BA . The importance of the γ/δ-T-cell and IL17/IL 23 pathway , for BA is currently probed. However, in groups of syngenic animals treated by the same batch of viruses BA tends to be inconstant and it is limited to extrahepatic bile ducts such as about the validity of the animal model is an issue.
2. The other direction of research does not primarily rely on experiments involving newborn animals: There are indications that during pregnancy the placental barrier may become permeable for maternal lymphocytes (e.g. by a faulty silencing of T-cell attracting chemokines in decidual stroma cells) and already in 2008 maternal lymphocytes have been demonstrated in livers of BA infants . Subsequently the phenomenon of materno-fetal microchimerism has come into focus of BA ethiology research: in the context of mixed materno-fetal immune reactions cells of maternal origin could misdirect the immature immune system of the infant into auto-immunity or act directly as effectors in a graft vs. host like fashion.

The importance of mesenteric and portal lymph nodes for maturation of the immune system during pregnancy has been reported recently . Moreover it has been demonstrated that flow the between liver and portal lymph nodes is bidirectional . In In mice the frequence of CD4+ and FoxP3+ regulatory T-cells was found to be linked to the mothers immune status. We thus hypothesized that the prominently swollen lymph nodes of BA infants which surgeons constantly encounter during Kasai's operation may hold a key to the better understanding of pathophysiological important lymphocyte trafficking mechanisms.