Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

Abstract

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.

Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis

“…Eosinophilic gastritis (EG) and gastroenteritis (EGE) are rare diseases of the gastrointestinal (GI) tract, affecting minimally 20 in 100,000 people worldwide (1). Prevalence has likely been underestimated because of the absence of a standard diagnosis and medical education (2,3) but is reported to be highest in children and adults ages 20-50 years, with a slightly higher incidence in men (1). These conditions belong to a larger spectrum of GI disorders known as eosinophilic gastrointestinal disorders (EGIDs), which are characterized by eosinophilic infiltration of the GI tract and debilitating GI symptoms (i.e., abdominal pain, nausea, vomiting, diarrhea, and dysphagia) (1).…”

A FACS-based approach to obtain viable eosinophils from human adipose tissue

“…A portion of SC-fat or OM-fat was formalin fixed and paraffin embedded. Five-micron slices underwent immunohistochemistry using monoclonal mouse anti-eosinophil peroxidase (EPX-mAb; clone 82.2.1 20 , 49 , a kind gift of Dr. E.A. Jacobsen, Mayo Clinic Arizona) with modifications.…”

“…High quality RNA isolation from eosinophils derived from peripheral blood has been described 20 and indeed we have succeeded in this procedure as well, however, this was accomplished with, at minimum, a full order of magnitude greater cell number than recovered from our adipose tissue samples. Given the multitude of inherent ribonucleases found within eosinophils 21 coupled with the scarcity of the cells in tissue, these techniques prove problematic for human tissue-derived eosinophils and RNA transcript analysis is not pursued 20 . To circumvent this limitation, we choose to address our focus toward an epigenetic evaluation of eosinophils.…”

Eosinophils of the horse: Part II: Eosinophils in clinical diseases

“… Do equine eosinophils express different phenotypes based upon tissue of residence, activation status and the horse’s health status? Eosinophil phenotypes are recognised in laboratory animals (Mesnil et al ; Percopo et al ) and human subjects (Ying et al ; Roth et al ; Khoury et al ). Few attempts have been made to identify eosinophil phenotypes in horses (Greenaway et al ; Riihimaki et al ).…”

“…Eosinophil‐associated diseases (EAD) are those in which the eosinophil plays a major, though often enigmatic, role. Rare but debilitating, these conditions are a research priority in human medicine (Bochner et al ; Khoury et al ; O'Sullivan and Bochner ). Horses suffer from EADs, including those that affect isolated body systems (Dixon et al ; Lankveld ; Uhlhorn et al ; Climent et al ; Loibl et al ; Archer et al ; Lassaline‐Utter et al ; Luethy et al ; Trimble et al ), as well as multisystemic eosinophilic epitheliotropic disease (MEED), which affects multiple body systems simultaneously (Bosseler et al ).…”