Clinical Trial: Maternal Microchimerism in Lymph Nodes of Infants With Biliary Atresia at Time of Kasai's Operation

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

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

Brief Summary:

Maternal microchimerism has been discussed as an etiological mechanism in infantile (perinatal) biliary atresia (BA). In Kasai's operation (resection of the liver hilum plaque followed by hepato-portoenterostomy) surgeons frequently encounter swollen portal and mesenteric lymph nodes.

Lymph nodes were sampled during Kasai' s operation and examined for maternal DNA.


Detailed Summary:

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 phenome
    Sponsor: Medizinische Hochschule Brandenburg Theodor Fontane

    Current Primary Outcome: Maternal DNA in offspring [ Time Frame: 3 months ]

    The presence of maternal DNA in the childs blood and lymph nodes is the endpoint


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Serum Bilirubin [ Time Frame: perioperatively ]
    • Composition of lymphocyte population in mesenteric lymph nodes [ Time Frame: 3 months ]


    Original Secondary Outcome: Same as current

    Information By: Medizinische Hochschule Brandenburg Theodor Fontane

    Dates:
    Date Received: November 13, 2014
    Date Started: November 2012
    Date Completion:
    Last Updated: November 14, 2014
    Last Verified: November 2014