- . Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses a cross-sectional study. The Lancet Gastroenterology and Hepatology. 2018; 3(7):477-488.
- Scientists at Cincinnati Children’s and the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) have discovered a new, personalized approach to diagnosing and treating rare food allergy disease, eosinophilic esophagitis (EoE). Diagnosing and treating rare diseases can be difficult in part due to widely dispersed and small populations of both patients and scientific experts. This lack of sufficient access to patients and expertise makes it challenging to understand the natural course of a rare disease and, in some cases, its different forms. To improve the understanding of EoE, scientists at Cincinnati Children’s teamed up with CEGIR, a group of national experts. The study, led by Tetsuo Shoda, PhD and Marc E. Rothenberg, MD, PhD, analyzed tissue samples from 185 child and adult patients with EoE from 10 sites associated with the consortium. Through detailing patients' individual genetic and clinical features and disease appearance through an endoscope and under a microscope, the researchers identified three distinct forms, called endotypes, of EoE that were each associated with different clinical and genetic characteristics. This advance will enable more personalized approaches to the treatment and care of patients with EoE and is a promising discovery for the field of eosinophilic gastrointestinal disorders.
- . Chromatin regulates IL-33 release and extracellular cytokine activity. Nature Communications. 2018; 9(1).
- Cytokines mediate cellular communication through activation of surface receptors upon extracellular release. The cytokine interleukin 33 (IL-33) is an epithelium-derived, pro-inflammatory alarmin with enigmatic nuclear localization and chromatin binding. Amongst alarmins, IL-33 is relatively unique in that it primes for allergic responses through its receptor, suppression of tumorigenicity 2 (ST2), which activates basophils, mast cells, eosinophils, group 2 innate lymphoid cells, and CD4+ T cells. The IL-33–ST2 axis is notably prominent in the pathogeneses of several allergic disorders, including asthma, atopic dermatitis, and eosinophilic esophagitis (EoE). A strong genetic association exists between allergy and the IL-33–ST2 axis, as variants in IL33 and IL1RL1 (encodes ST2) confer risk for several allergic diseases. Research in the laboratory of Marc E. Rothenberg, MD, PhD and led by MD-PhD student Jared Travers, investigated the functional properties of nuclear IL-33. They found that IL-33 binding to chromatin regulated the mobility, release, and activity of IL-33. In fact, IL-33 was released from cells while being bound to chromatin. They propose that chromatin binding is a posttranslational mechanism that regulates the releasability and ST2-mediated bioactivity of IL-33, thereby providing a paradigm to further understand the enigmatic functions of nuclear cytokines and potential points of intervention.
- . Analysis of eosinophilic esophagitis in children with repaired congenital esophageal atresia. Journal of Allergy and Clinical Immunology. 2019; 143(4):1455-1464.e2.
- Led by Assistant Professor Ting Wen, MD, PhD, a collaborative team of researchers in Australia and at Cincinnati Children's pursued the preliminary observation of a high prevalence of eosinophilic esophagitis (EoE) in patients after repair of esophageal atresia (EA). Analyzing molecular transcriptomes obtained using the EoE Diagnostic Panel, a diagnostic array co-invented by Ting Wen, MD, PhD and Marc Rothenberg, MD, PhD, they identified that patients with EA have a significantly increased risk, 364 fold, of EoE. Patients with EoE and EA together had a similar molecular profile to that of patients with EoE alone. The baseline dysregulation of epithelial barrier and type 2-associated genes identified in EA monomorbidity in this study might explain the higher EoE prevalence in patients with EA, as these are also dysregulated in EoE and hypothesized to be predisposing factors in development of EoE. This new knowledge will improve timely diagnosis and management of the rare condition EoE in children who have undergone repair of congenital EA and help to better understand EoE.
- . Eosinophil progenitor levels correlate with tissue pathology in pediatric eosinophilic esophagitis. Journal of Allergy and Clinical Immunology. 2019; 143(3):1221-1224.e3.
- Disease management and improved therapeutics for patients with eosinophilic esophagitis (EoE), a rare, chronic, allergic condition, have been impeded by lack of less-invasive means of monitoring disease activity and remission. The current standard of care requires invasive, serial endoscopies to assess tissue pathology as a measure of disease activity. Research efforts, led by Justin T. Schwartz, MD, PhD and fueled by basic research in eosinophils and their progenitors by Patricia C. Fulkerson, MD, PhD and Marc E. Rothenberg, MD, PhD, have identified that eosinophil progenitor levels in the blood correlate with tissue pathology changes in children with EoE. Should this promising finding be replicated and confirmed in further studies in larger cohorts, it would represent a paradigm shift in the care of patients with EoE, drastically reducing care expenses and the need for anesthesia and potentially improving quality of life.
- . AR101 Oral Immunotherapy for Peanut Allergy.. The New England journal of medicine. 2018; 379(21):1991-2001.
- The prevalence of peanut allergy in the United States and other industrialized countries is on the rise and accounts for the majority of deaths related to food allergy. The lack of approved treatment for peanut allergy leaves families depending on the standard of care of strict elimination diet and timely administration of rescue medications in case of an allergic reaction to accidental exposure. The Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization (PALISADE) was an international, randomized, double-blind, placebo-controlled, phase 3 trial that evaluated the efficacy and safety of AR101, a new peanut-derived, oral biologic drug delivering a daily maintenance dose of 300 mg of peanut protein to induce immune tolerance, in children and adolescents with peanut allergy. Director of the Food Allergy Program at Cincinnati Children's, Amal H. Assa'ad, MD, contributed to this critical, collaborative work and was the third-highest recruiter. This trial demonstrated that oral immunotherapy with AR101 for children and adolescents who were highly allergic to peanut resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. These findings are helpful in progressing this treatment toward FDA approval.
Publications
Top 5 Publications
3333 Burnet Avenue, Cincinnati, Ohio 45229-3026
© 1999-2024 Cincinnati Children's Hospital Medical Center. All rights reserved.
