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The Role of Human Leukocyte Antigen Alleles and Maternal Microchimerism in Very-Early-Onset Ulcerative Colitis in

Masanori Toda1, Keisuke Jimbo2, Mitsuyoshi Suzuki2

  • 1Department of Pediatrics, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Inflammatory Bowel Diseases
|March 10, 2025
PubMed

Insights

Very-early-onset ulcerative colitis (VEO-UC) involves specific human leukocyte antigen (HLA) alleles and maternal microchimerism (MMc). These genetic and maternal immune factors contribute to VEO-UC pathogenesis in Japanese children.

Area of Science:

  • Immunology
  • Genetics
  • Gastroenterology

Background:

  • Very-early-onset ulcerative colitis (VEO-UC) is a severe form of inflammatory bowel disease presenting before age 6.
  • VEO-UC exhibits distinct genetic and immunological characteristics compared to typical pediatric UC.
  • Investigating human leukocyte antigen (HLA) alleles and maternal microchimerism (MMc) is crucial for understanding VEO-UC pathogenesis.

Purpose of the Study:

  • To examine the association of specific HLA alleles with VEO-UC in a Japanese population.
  • To investigate the presence and role of maternal microchimerism (MMc) in VEO-UC intestinal tissues.
  • To elucidate the interplay of genetic and maternal immune factors in VEO-UC development.

Main Methods:

  • Case-control study involving 27 VEO-UC patients.
  • Human leukocyte antigen (HLA) typing using polymerase chain reaction-sequence-specific oligonucleotide probing (PCR-SSOP).
  • Immunohistochemistry and fluorescence in situ hybridization to detect maternal microchimerism (MMc).

Main Results:

  • Prevalence of HLA-B52 and HLA-DR15 was higher in VEO-UC cases compared to the general Japanese population.
  • Maternal microchimerism (MMc) was detected in intestinal tissues of three VEO-UC patients.
  • Maternal HLA concordance with VEO-UC associated alleles suggested maternal immune involvement.

Conclusions:

  • VEO-UC shares genetic predispositions with adult UC, including associations with HLA-B52 and HLA-DR15.
  • Maternal immune contributions, evidenced by MMc, play a role in VEO-UC pathogenesis.
  • Further research is needed to develop targeted therapies for VEO-UC based on genetic and immunological mechanisms.
Abstract

Keywords:
human leukocyte antigenmaternal microchimerismpediatricsulcerative colitis

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