A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

作者：Ta‐Chiang Liu, Kelley VanBuskirk, Asad Ali, Paul Kelly, Lori R. Holtz, Ömer Yılmaz, Kamran Sadiq, Najeeha Talat Iqbal, Beatrice Amadi, Sana Syed, Tahmeed Ahmed, Sean R. Moore, I. Malick Ndao, Michael H. Isaacs, John D. Pfeifer, Hannah E Atlas, Phillip I. Tarr, Donna M. Denno, Christopher A. Moskaluk · 发表于：PLoS neglected tropical diseases · 年份：2020 · DOI：10.1371/journal.pntd.0007975 · 被引用次数：87 · 研究领域：Celiac Disease Research and Management、Gastrointestinal motility and disorders、Microscopic Colitis

BACKGROUND: A major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity. METHODS: Duodenal endoscopic biopsies from two cohorts where EED is prevalent (Pakistan, Zambia) and North American children with and without gluten sensitive enteropathy (GSE) were processed for routine hematoxylin & eosin (H&E) staining, and scanned to produce whole slide images (WSIs) which we shared among study pathologists via a secure web browser-based platform. A semi-quantitative scoring index composed of 11 parameters encompassing tissue injury and response patterns commonly observed in routine clinical practice was constructed by three gastrointestinal pathologists, with input from EED experts. The pathologists then read the WSIs using the EED histology index, and inter-observer reliability was assessed. The histology index was further used to identify within- and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype. RESULTS: Eight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet's AC 0.9...