Eosinophil-based Assays
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| Over the past several years there has been a remarkable increase in the number of patients being diagnosed with a variety of eosinophilic diseases. Here at Cincinnati Children's, we have launched the Cincinnati Center for Eosinophilic Disorders. The mission of the CCED is to provide state-of-the-art patient care linked to innovative bench and bed-side research. As such, studies are being conducted to identify noninvasive biomarkers for disease diagnosis and staging, as well as genetic and molecular-immunological tests with diagnostic and therapeutic relevance. Coined as "Eosinophil-based Laboratory Tests" two assays have recently been added to our menu of testing, while others are planned for release in the future (section contributed by Dr. Marc Rothenberg). |
| EE Treatment |
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| Anti-GERD therapy |
| Specific food elimination |
| Exclusive elemental (amino-acid) diet |
| Topical (ingested) corticosteroids |
| Systemic corticosteroids |
| Anti-IL-5 (research) |
| EE Further Reading |
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| Blanchard et al. J Clin Invest. 2006; 116:536. |
| Konikoff et al. Clin Gastroenterol Hepatol. 2006; 4:1328. |
| Furuta et al. Aliment Pharmacol Ther. 2006; 15:173. |
| Blanchard et al. J Allergy Clin Immunol. 2006; 118:1045. |
Eosinophil-Based Laboratory Tests
In contrast to other parts of the gastrointestinal tract, the normal esophagus does not contain eosinophils, and thus demonstrating eosinophils in this particular anatomical structure is abnormal. Among the disorders to consider (e.g. eosinophilic gastroenteritis, chronic esophagitis, parasitic infection, hypereosinophilic syndromes and gastroesophageal reflux disease [GERD]), eosinophilic esophagitis (EE) is characterized by particularly high eosinophil counts. Current concepts in EE indicate that this is an emerging disorder, likely due to both an increase in disease incidence and an increased recognition of EE as a unique disorder. In children, the incidence is between (at least) 1:1500 and 1:10000, with a peak incidence among Caucasians from industrialized countries. The complex pathogenesis of EE is being unraveled by detailed multidisciplinary clinical studies, genome-wide gene expression profiling, as well as the use of experimental animal models.
Although a proportion of patients with EE are non-atopic, allergic components, demonstrated by food and/or aeroallergen hypersensitivity (extrinsic contribution), as well as a local overproduction of Th2-type cytokines (e.g. IL-4, IL-5, IL-13) in the esophagus (intrinsic contribution), constitute important aspects of the pathogenesis. The gene profiling approach has provided important clues to the pathogenesis, showing a relatively uniform gene transcription profile ("transcriptome") in both atopic and non-atopic EE patients (also conserved across age and sex), as well as a potential role for eotaxin-3, the most highly induced gene in EE tissues.
Clinical manifestations of EE include chest and abdominal pain, dysphagia, heartburn, vomiting, weight loss and food impaction. It is becoming apparent that EE requires longterm therapy and treatment guidelines are currently being developed (see side box). Therapy that modifies disease pathogenesis is highly desirable. In the context of the considerable diagnostic and therapeutic challenges of EE, it is important to have noninvasive tools to complement and/or replace (serial) endoscopic biopsy examinations, in order to diagnose and distinguish EE from other disorders (see above), as well to follow its natural history and monitor response to treatment, especially in the framework of clinical trials using novel therapeutics.
EDN and Eotaxin-3
A series of studies have identified several biomarkers of promise, including (combinations of) peripheral blood absolute eosinophil count (AEC) and plasma levels of eosinophil-derived neurotoxin (EDN) and eotaxin-3. EDN is a major constituent of eosinophil granules and its expression is unique to eosinophils. It is a cytotoxic granule with ribonuclease activity, released in a variety of bodily fluids (serum, urine, stool) in certain inflammatory conditions (e.g. asthma, inflammatory bowel disease). Eotaxin-3 is one of a family of eosinophilspecific chemokines, which as mentioned above, has been identified in tissue-specific gene profiling assays as an important etiologic factor in the pathogenesis of EE. Moreover, the levels of eotaxin-3 transcripts correlate with disease severity, and appear to be linked to a single nucleotide polymorphism (SNP) in the eotaxin-3 gene (to be discussed in a future Newsletter edition).
Both molecules are measured in plasma using ELISA methodology and are compared to age-appropriate healthy control values. In combination with diagnostic endoscopy and other biomarkers, EDN and eotaxin-3 may demonstrate usefulness in the diagnostic process of EE, as well as in monitoring its natural history and response to therapeutic interventions, particularly if these target the pathogenesis of EE.
