Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, University of California, La Jolla, California, USA.
J Leukoc Biol. 2018 Jul;104(1):69-83. doi: 10.1002/JLB.5MR0118-028R. Epub 2018 Apr 19.
Eosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes. Researchers with expertise in eosinophil biology and eosinophil-related diseases reviewed the state of current eosinophil research, resources, progress, and unmet needs in the field since the 2012 meeting of the NIH Taskforce on the Research of Eosinophil-Associated Diseases (TREAD). RE-TREAD focused on gaps in basic science, translational, and clinical research on eosinophils and eosinophil-related pathogenesis. Improved recapitulation of human eosinophil biology and pathogenesis in murine models was felt to be of importance. Characterization of eosinophil phenotypes, the role of eosinophil subsets in tissues, identification of biomarkers of eosinophil activation and tissue load, and a better understanding of the role of eosinophils in human disease were prioritized. Finally, an unmet need for tools for use in clinical trials was emphasized. Histopathologic scoring, patient- and clinician-reported outcomes, and appropriate coding were deemed of paramount importance for research collaborations, drug development, and approval by regulatory agencies. Further exploration of the eosinophil genome, epigenome, and proteome was also encouraged. Although progress has been made since 2012, unmet needs in eosinophil research remain a priority.
嗜酸性粒细胞相关疾病（EADs）是罕见的、异质性疾病，其特征是组织和/或外周血中存在嗜酸性粒细胞，导致免疫病理学改变。组织受累的异质性、缺乏足够的动物模型、在嗜酸性粒细胞研究方面的技术挑战，以及缺乏标准化的组织病理学方法，这些都阻碍了基础研究的进展。此外，由于缺乏原发性和替代终点、生物标志物以及经过验证的患者报告结局，针对罕见 EADs 的临床试验和药物开发受到限制。具有嗜酸性粒细胞生物学和嗜酸性粒细胞相关疾病专业知识的研究人员回顾了自 2012 年 NIH 嗜酸性粒细胞相关疾病研究工作组（TREAD）会议以来，该领域中嗜酸性粒细胞研究、资源、进展和未满足需求的现状。RE-TREAD 重点关注嗜酸性粒细胞和嗜酸性粒细胞相关发病机制的基础科学、转化和临床研究中的差距。人们认为，在小鼠模型中更好地再现人类嗜酸性粒细胞生物学和发病机制非常重要。嗜酸性粒细胞表型的特征、组织中嗜酸性粒细胞亚群的作用、嗜酸性粒细胞激活和组织负荷的生物标志物的鉴定，以及更好地了解嗜酸性粒细胞在人类疾病中的作用，这些都被列为优先事项。最后，强调了临床试验中工具的未满足需求。组织病理学评分、患者和临床医生报告的结局以及适当的编码被认为对研究合作、药物开发和监管机构的批准至关重要。进一步探索嗜酸性粒细胞的基因组、表观基因组和蛋白质组也受到鼓励。尽管自 2012 年以来已经取得了进展，但嗜酸性粒细胞研究中的未满足需求仍然是优先事项。
