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Diagnosis of Hirschsprung's Disease by Immunostaining Rectal Suction Biopsies for Calretinin, S100 Protein and Protein Gene Product 9.5
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Maternal microchimerism in Hirschsprung's disease.

Autumn S Kiefer1, Tara R Lang, Molly S Hein

  • 1Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

American Journal of Perinatology
|November 23, 2011
PubMed
Summary

Maternal cells are more prevalent in Hirschsprung

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Area of Science:

  • Gastroenterology and Immunology

Background:

  • Hirschsprung's disease (HD) is characterized by absent ganglion cells in the distal rectum, leading to severe constipation.
  • The pathogenesis of HD involves an unfavorable microenvironment potentially influenced by maternal factors.
  • Maternal microchimerism, the transfer of cells between mother and fetus, is a potential contributor to immune-mediated conditions.

Purpose of the Study:

  • To investigate the presence and characteristics of maternal chimeric cells in the aganglionic bowel of patients with Hirschsprung's disease.
  • To determine if maternal microchimerism plays a role in the destruction of enteric neurons in HD.

Main Methods:

  • Analysis of intestinal biopsies and resections from male patients with HD, chronic constipation, and bowel atresia.
  • Utilizing fluorescence in situ hybridization (FISH) to identify XX/XY chimeric cells.
  • Studying the location and immunophenotype of identified chimeric cells.

Main Results:

  • Chimeric cells were found more frequently in the small intestine and rectum compared to the appendix and colon.
  • Patients with HD exhibited a higher number of chimeric cells per field than control groups.
  • In HD cases, chimeric cells were primarily located in the submucosa and outer longitudinal muscle layer, with over 40% identified as inflammatory.

Conclusions:

  • Aganglionic bowel tissue in Hirschsprung's disease contains a greater number of maternal chimeric cells.
  • The clustering of these cells near areas of absent ganglia supports their potential role in allo-autoimmune responses contributing to HD pathogenesis.
  • Findings suggest maternal microchimerism may be implicated in the immune-mediated destruction of enteric neurons in Hirschsprung's disease.