Featured Research

from universities, journals, and other organizations

Mysterious esophagus disease is autoimmune after all

Date:
July 29, 2014
Source:
KU Leuven
Summary:
Achalasia is a rare disease – it affects 1 in 100,000 people – characterized by a loss of nerve cells in the esophageal wall. While its cause remains unknown, a new study confirms for the first time that achalasia is autoimmune in origin.

Achalasia is a rare disease -- it affects 1 in 100,000 people -- characterized by a loss of nerve cells in the esophageal wall. While its cause remains unknown, a new study by a team of researchers at KU Leuven in Belgium, the University of Bonn in Germany and other European institutions confirms for the first time that achalasia is autoimmune in origin. The study, published on 6 July in Nature Genetics, is an important step towards unraveling the mysterious disease.

Related Articles


When we swallow, a sphincter in the lower esophagus opens, allowing food to enter the stomach. Nerve cells in the esophageal wall control the opening and closing of this sphincter, but in people with achalasia, these nerve cells gradually disappear. Without these cells, the esophageal sphincter fails to relax, causing food to accumulate in the esophagus. This results in swallowing problems, regurgitation, vomiting, nighttime coughing, chest pain and weight loss.

Because so little is known about achalasia, current treatments are limited to stretching the esophageal sphincter endoscopically with a balloon or surgically cutting the sphincter. But while these treatments can help alleviate the disease's symptoms, they do not address its cause.

Researchers have long suspected that an autoimmune response lies at the root of the disease, but an explanation for why the immune system of people with achalasia responds as it does remains elusive.

One possible explanation is that esophageal nerve cells are targeted by the body's defenses due to a miscued immune response to an earlier viral infection -- the immune system mistakes the nerve cells for the virus and attacks them.

Genetic risk

Based on their results, the researchers in this study now think that genetics may play a more important role than previously thought in determining who is at risk for achalasia. Because the disease is so rare, cohorts in previous genetic studies have been too small (less than 300 patients) to draw significant conclusions.

Together with German colleagues, researchers at KU Leuven studied the DNA of 1,506 achalasia patients and 5,832 healthy volunteers from Central and Southern Europe. The study is the first systematic, genome-wide association study on achalasia and involves the largest cohort ever analyzed for the disease.

The researchers genotyped 196,524 tiny differences -- called single-nucleotide polymorphisms, or SNPs, pronounced 'snips' -- in the immune-related DNA of people with achalasia, and compared the results with the DNA of the healthy volunteers. 33 SNPs were found to be associated with achalasia.

Pinpointed

Surprisingly, all 33 were located in the so-called 'major histocompatibility complex' (MHC) region of chromosome 6, the most gene-dense region in the human genome. This region is also known to be associated with other autoimmune disorders, including multiple sclerosis, type 1 diabetes and lupus. This evidence was enough for the researchers to confirm that achalasia is itself an autoimmune disease.

The researchers also pinpointed a specific string of amino acids inserted in the DNA of people with achalasia but not in the controls. The string, 8-amino acids long, is located in the cytoplasmic tail of HLA DQβ1. Moving forward, the researchers will examine the functional effects of these extra amino acids -- in the hope of finding the cause, and eventually the cure, of this enigmatic disease.


Story Source:

The above story is based on materials provided by KU Leuven. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ines Gockel, Jessica Becker, Mira M Wouters, Stefan Niebisch, Henning R Gockel, Timo Hess, David Ramonet, Julian Zimmermann, Ana González Vigo, Gosia Trynka, Antonio Ruiz de León, Julio Pérez de la Serna, Elena Urcelay, Vinod Kumar, Lude Franke, Harm-Jan Westra, Daniel Drescher, Werner Kneist, Jens U Marquardt, Peter R Galle, Manuel Mattheisen, Vito Annese, Anna Latiano, Uberto Fumagalli, Luigi Laghi, Rosario Cuomo, Giovanni Sarnelli, Michaela Müller, Alexander J Eckardt, Jan Tack, Per Hoffmann, Stefan Herms, Elisabeth Mangold, Stefanie Heilmann, Ralf Kiesslich, Burkhard H A von Rahden, Hans-Dieter Allescher, Henning G Schulz, Cisca Wijmenga, Michael T Heneka, Hauke Lang, Karl-Peter Hopfner, Markus M Nöthen, Guy E Boeckxstaens, Paul I W de Bakker, Michael Knapp, Johannes Schumacher. Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia. Nature Genetics, 2014; 46 (8): 901 DOI: 10.1038/ng.3029

Cite This Page:

KU Leuven. "Mysterious esophagus disease is autoimmune after all." ScienceDaily. ScienceDaily, 29 July 2014. <www.sciencedaily.com/releases/2014/07/140729073644.htm>.
KU Leuven. (2014, July 29). Mysterious esophagus disease is autoimmune after all. ScienceDaily. Retrieved March 28, 2015 from www.sciencedaily.com/releases/2014/07/140729073644.htm
KU Leuven. "Mysterious esophagus disease is autoimmune after all." ScienceDaily. www.sciencedaily.com/releases/2014/07/140729073644.htm (accessed March 28, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, March 28, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
House Ready to Pass Medicare Doc Bill

House Ready to Pass Medicare Doc Bill

AP (Mar. 26, 2015) — In rare bipartisan harmony, congressional leaders pushed a $214 billion bill permanently blocking physician Medicare cuts toward House passage Thursday, moving lawmakers closer to resolving a problem that has plagued them for years. (March 26) Video provided by AP
Powered by NewsLook.com
What's Different About This Latest Ebola Vaccine

What's Different About This Latest Ebola Vaccine

Newsy (Mar. 26, 2015) — A whole virus Ebola vaccine has been shown to protect monkeys exposed to the virus. Here&apos;s what&apos;s different about this vaccine. Video provided by Newsy
Powered by NewsLook.com
HIV Outbreak Prompts Public Health Emergency In Indiana

HIV Outbreak Prompts Public Health Emergency In Indiana

Newsy (Mar. 26, 2015) — Indiana Gov. Mike Pence says he will bring additional state resources to help stop the epidemic. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins