Published Online: April 22, 2013
Eosinophilic Esophagitis (EoE) is a chronic inflammatory disorder of the esophagus that fundamentally and negatively alters the typically pleasurable experience of eating food. Prior studies of esophageal biopsy samples have identified members of a particular cellular signaling pathway, the TGF-β1 pathway, in patients with EoE. This finding is of interest as certain inherited connective tissue disorders (CTDs) such as the Marfan, Loeys-Dietz, and Ehlers-Danlos syndromes, have each been associated with changes in the TGF-β1 pathway and disruption of collagen, a protein critical to connective tissue formation. Notably, patients with these syndromes often suffer from chronic gastrointestinal complaints.
In an Original Research Article in The Journal of Allergy & Clinical Immunology (JACI), Drs. J. Pablo Abonia, Marc E. Rothenberg, and their colleagues at the Cincinnati Center for Eosinophilic Disorders (CCED) (www.cincinnatichildrens.org/cced) at Cincinnati Children’s Hospital Medical Center describe a new finding regarding patients with EoE and the aforementioned CTDs. The authors hypothesized that patients with these specific CTDs may be overrepresented in the EoE population, meaning that an individual with EoE may be more likely to have a CTD than an individual without EoE. The authors evaluated data from non-EoE and EoE populations through the use of anonymized electronic medical records (EMRs) incorporating more than a million patients and of an eosinophilic gastrointestinal disease-focused research database (E-rdb) with more than a thousand patients with EoE.
The researchers found that the risk of having a CTD was increased approximately 8-fold in the EoE population relative to the general population. Not only was the risk of CTD increased for patients with EoE, but patients with EoE and CTD (EoE-CTD) also differed from patients with standard EoE (no evidence of CTD). Patients with EoE-CTD had a lower body mass index (BMI) and differences in mRNA expression, in particular the decreased expression of a collagen gene previously implicated in Ehlers-Danlos Syndrome and thought to bind TGF-β1. These physical manifestations of EoE-CTD likely represent a broad systemic effect of collagen disruption present uniquely in the EoE-CTD population.
The authors further explain that these findings may lead to new therapeutic options for patients with EoE through the use of already available agents that reduce the activity of the TGF-β1 pathway. In particular, they propose that losartan, an FDA-approved drug for hypertension that is known to lower TGF-β1, may be useful for EoE and have launched a clinical trial that is currently enrolling patients, as described on the ClinicalTrials.gov website.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.