Navigation Links
Study finds cause of mysterious food allergy, suggests new treatment strategy
Date:7/13/2014

New research in Nature Genetics identifies a novel genetic and molecular pathway in the esophagus that causes eosinophillic esophagitis (EoE), opening up potential new therapeutic strategies for an enigmatic and hard-to-treat food allergy.

EoE is a chronic inflammatory disorder of the esophagus. The condition is triggered by allergic hypersensitivity to certain foods and an over-accumulation in the esophagus of white blood cells called eosinophils (part of the body's immune system). EoE can cause a variety of gastrointestinal complaints including reflux-like symptoms, vomiting, difficulty swallowing, tissue scarring, fibrosis, the formation of strictures and other medical complications.

Reporting their results online, the multi-institutional team of researchers was led by scientists at Cincinnati Children's Hospital Medical Center. The authors identified a molecular pathway specific to epithelial tissue in the esophagus involving a gene called CAPN14, which they found becomes dramatically up-regulated in the disease process.

Epithelial cells help form the membrane of the esophagus. The scientists report that when these cells were exposed to a well-known molecular activator of EoE an immune hormone called Interleukin 13 (IL-13) it caused dramatic up-regulation of CAPN14. The researchers said this happened in what they described as an epigenetic hotspot for EoE on the cells' chromosomes.

CAPN14 encodes an enzyme in the esophagus that is part of the disease process called calpain14, according to Marc E. Rothenberg, MD, senior investigator on the study and director of the Center for Eosinophilic Disorders at Cincinnati Children's. Because caplain14 can be targeted and inhibited by drugs, the study opens up new therapeutic strategies for researchers.

"In a nutshell, we have used cutting edge genomic analysis of patient DNA as well as gene and protein analysis to explain why people develop EoE," Rothenberg explained. "This is a major breakthrough for this condition and gives us a new way to develop therapeutic strategies by modifying the expression of caplain14 and its activity. Our results are immediately applicable to EoE and have broad implications for understanding eosinophilic disorders as well as allergies in general."

The study follows years of research into EoE by Rothenberg's laboratory, including the development of novel modeling systems for the disease, and extensive multi-institutional collaboration through the National Institutes of Health's Consortium of Food Allergy Researchers. Other key collaborators on the current study include first author, Leah Kottyan, PhD, a researcher at the Center for Autoimmune Genomic Etiology at Cincinnati Children's, and co-senior investigator John Harley, MD, PhD, director of the Center of Autoimmune Genomic Etiology .

Rothenberg's lab years ago identified IL-13 as a key molecular contributor to the allergic reaction process in EoE. His team has since identified a number of related genes and molecular pathways linked to the disease, and they have tested drugs that inhibit IL-13 in an attempt to manage EoE severity.

"The current study links allergic responses mediated through IL-13 with an esophageal specific pathway, and answers a long-standing question in the allergy field of why people develop tissue specific disease manifestations," Rothenberg explained. "We have uncovered that this can be explained by the interplay of genetic susceptibility elements in allergic sensitization pathways with the newly discovered esophageal specific pathway. Thus, two steps are necessary, one dictated by allergy and one dictated by calpain14 in the esophagus."

The researchers used computer bioinformatics to conduct a genome-wide association study that analyzed 2.5 million genetic variants in thousands of individuals with and without EoE. This allowed the authors to identify the genetic susceptibility within the CAPN14 gene. The investigators were surprised to learn that CAPN14 was specifically expressed in the esophagus, compared with 130 other tissues in the body they analyzed.

Rothenberg said the findings open a new way to consider therapeutic options because calpain14 is an enzyme that can be inhibited by drugs, which means it may be possible to modify the expression and activity of calpain14. Some chemical compounds already exist that block the activity of calpains, although the researchers do not yet know the exact function of calpain14, as very little has been published about it.


'/>"/>

Contact: Jim Feuer
jim.feuer@cchmc.org
513-636-4656
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

Related medicine news :

1. Study Suggests Vaccine May Help Kids With Brain Cancer
2. Study reveals how cancer drug causes diabetic-like state
3. Coffee Drinking in Pregnancy Wont Lead to Sleepless Baby: Study
4. Lower GI problems plague many with rheumatoid arthritis, Mayo Clinic study finds
5. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
6. No Added Cancer Risk From Hip Replacement Materials: Study
7. Reported Decline in U.S. Pneumonia Deaths May Be False: Study
8. Early Study Finds Some Promise for Lung Cancer Vaccine
9. Narcissists Often Ace Job Interviews, Study Finds
10. Sexual objectification of female artists in music videos exists regardless of race, MU study finds
11. Soy may alleviate hot flashes in menopause, large-scale study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term ... long-term care insurance companies have a waiver for care if the client has a ... when the family pays for care, is often waived, so the benefits from their ...
(Date:10/13/2017)... NY (PRWEB) , ... October 13, 2017 , ... Ellevate ... people in business to advocate for action towards gender equality at their inaugural Summit ... from around the globe, and reached a social audience of over 3 million. To ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at The House ... most popular and least understood books in the Holy Scriptures, Revelation. The Book of ... baffled scholars for centuries. Many have tossed it off as mere rubbish, but Yisrayl ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... ... DevOps and Agile Software Development, has been awarded a contract by the Center ... Purchase Agreement (BPA) aims to accelerate the enterprise use of Agile methodologies in ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... “America On ... Christian identity. “America On The Brink” is the creation of published author, William ... several great-grandchildren. As a WWII veteran, he spent thirty years in the Navy. ...
Breaking Medicine News(10 mins):
(Date:9/22/2017)... ROCKVILLE, Md. , Sept. 22, 2017  As ... by Republican Senators Bill Cassidy (R-LA) and ... Kalorama Information notes that the medical device industry is ... the medical device tax, the 2.3% excise tax on ... Act.  But they also want covered patients, increased visits ...
(Date:9/19/2017)... Mich. , Sept. 19, 2017 HistoSonics, Inc., a venture-backed medical device company ... destruction of targeted tissues, announced three leadership team developments today:   ... PhD ... ... Veteran medical device executive Josh ...
(Date:9/18/2017)... KALAMAZOO, Mich. , Sept. 18, 2017 ... , and OptiMed Specialty Pharmacy of Kalamazoo, ... offer a strategic hub service that expedites and streamlines ... personal spirometer, Spiro PD 2.0, and wellness management services.  ... is a medical device used to measure lung function ...
Breaking Medicine Technology: