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

IF 4.5 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Inflammatory Bowel Diseases Pub Date : 2025-03-10 DOI:10.1093/ibd/izaf048

Masanori Toda, Keisuke Jimbo, Mitsuyoshi Suzuki, Masumi Nagata, Nobuyasu Arai, Kaori Tokushima, Eri Miyata, Yuka Nagano, Yuki Koike, Keiichi Uchida, Takahiro Kudo, Yuji Toiyama, Toshiaki Shimizu

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引用次数: 0

Abstract

Background: Very-early-onset ulcerative colitis (VEO-UC) is a severe form of inflammatory bowel disease that manifests before the age of 6 years. Compared to typical pediatric UC, it is characterized by distinct genetic and immunological factors. This study aimed to investigate the roles of specific human leukocyte antigen (HLA) alleles and maternal microchimerism (MMc) in the pathogenesis of VEO-UC in a Japanese population.

Methods: This study included 27 VEO-UC patients, including 4 patients treated with colorectal resection. HLA typing was performed by polymerase chain reaction-sequence-specific oligonucleotide probing (PCR-SSOP) and compared with the Japanese general population. Immunohistochemistry and fluorescence in situ hybridization were used to evaluate MMc in intestinal tissues. Statistical comparisons of HLA were performed against data from the general Japanese population, with Bonferroni corrections applied to handle multiple comparisons.

Results: HLA-B52 and HLA-DR15 were more prevalent in cases of VEO-UC than in the general Japanese population, although the statistical significance decreased after the Bonferroni correction. MMc was found in the intestinal tissues of three VEO-UC cases, whereas it was absent in the control UC cases. Maternal HLA concordance with specific alleles associated with VEO-UC was noted in several cases, suggesting maternal immune involvement in the pathogenesis of the disease.

Conclusions: VEO-UC seems to share genetic traits with adult UC, such as an association with HLA-B52 and HLA-DR15, and is also affected by maternal immune contributions, as shown by the presence of MMc in the affected tissues. These findings highlight the complex interaction between genetic and immunological factors in the pathogenesis of VEO-UC and underscore the need for further research to develop targeted therapeutic strategies that address these mechanisms.

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来源期刊

Inflammatory Bowel Diseases 医学-胃肠肝病学

CiteScore

9.70

自引率

6.10%

发文量

462

审稿时长

1 months

期刊介绍： Inflammatory Bowel Diseases® supports the mission of the Crohn''s & Colitis Foundation by bringing the most impactful and cutting edge clinical topics and research findings related to inflammatory bowel diseases to clinicians and researchers working in IBD and related fields. The Journal is committed to publishing on innovative topics that influence the future of clinical care, treatment, and research.