Featured Research

from universities, journals, and other organizations

Abnormal Immune Cells May Cause Unprovoked Anaphylaxis

Date:
November 10, 2007
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
Two new clinical reports shed light on why some people suffer from recurrent episodes of idiopathic anaphylaxis -- a potentially life-threatening condition of unknown cause characterized by a drop in blood pressure, fainting episodes, difficulty in breathing, and wheezing.

Two new clinical reports shed light on why some people suffer from recurrent episodes of idiopathic anaphylaxis--a potentially life-threatening condition of unknown cause characterized by a drop in blood pressure, fainting episodes, difficulty in breathing, and wheezing.

In some of these individuals, researchers have found mast cells (a type of immune cell involved in allergic reactions) that have a mutated cell surface receptor that disturbs normal processes within the cell. Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), say the association of this mutation with unprovoked anaphylaxis is striking. The hope is that these individuals may respond to inhibitors targeting the mutated cell surface receptor.

While some people suffer anaphylaxis as part of a serious allergic reaction, in two out of three people, anaphylaxis has no known cause and thus the anaphylactic reaction is called idiopathic.

Anaphylaxis occurs when mast cells release large quantities of chemicals (histamines, prostaglandins and leukotrienes) that cause blood vessels to leak, bronchial tissues to swell and blood pressure to drop. Resulting conditions such as shock and unconsciousness usually resolve in most people treated with epinephrine (adrenaline) and first aid measures. In rare cases, however, death may occur.

Abnormally low blood pressure and fainting episodes are also features of mastocytosis--a disease in which people have an excessive number of mast cells. Several years ago, Dean Metcalfe, M.D., chief of the Laboratory of Allergic Diseases at NIAID, Cem Akin, M.D., Ph.D., and their NIAID colleagues decided to find out whether idiopathic anaphylaxis might have a genetic trigger related to that seen in mastocytosis. It is known that systemic mastocytosis in adults often results from a mutation in the Kit receptor found on the surface of mast cells, a discovery first made by Dr. Metcalfe's team in 1995.

The mutation causes an abnormal growth of mast cells, as is observed in bone marrow biopsies of patients with mastocytosis. So the NIAID team asked, if the Kit mutation could make mast cells grow and cause mastocytosis, and this was associated with anaphylactic reactions, could the same mutation predispose mast cells to release chemicals responsible for idiopathic anaphylaxis?

In a two-year study conducted at the NIH Clinical Center, the researchers examined 48 patients diagnosed with mastocytosis with or without associated anaphylaxis, 12 patients with idiopathic anaphylaxis, and 12 patients with neither disease. Within the group of 12 patients who had idiopathic anaphylaxis, five were found with evidence of a disorder in a line of mast cells (clonal mast cell disorder). The researchers looked for evidence of a Kit mutation in three patients by analyzing bone marrow samples, and all three samples yielded a positive result. The findings demonstrate that some patients with idiopathic anaphylaxis have an aberrant population of mast cells with mutated Kit.

"We believe the mutation may be predisposing people to idiopathic anaphylaxis," says Dr. Metcalfe. "Our findings suggest that in patients with idiopathic anaphylaxis as well as in people with severe allergies, we should look for critical genetic mutations that may change the way a mast cell reacts."

Dr. Metcalfe and his NIAID colleagues report their findings in two journals. The study that appears in an early online edition in Blood describes the presence of an abnormal mast cell population in a subset of patients with idiopathic anaphylaxis. The findings about the mechanism leading to mass cell activation by Kit and the IgE receptor responsible for allergic reactions appear online in Cellular Signalling.

According to the NIAID team, both Kit and the IgE receptor responsible for allergic reactions activate mast cells via a common interior protein of mast cells. They also found that the mutated Kit markedly elevates the activity of that protein, which results in increased cell signaling.

The scientists are now looking to see if artificial mast cells with mutated Kit behave or release chemicals in a manner different from normal mast cells, and also if they respond to inhibitors targeting Kit.

Journal references: C Akin et al. Demonstration of an aberrant mast cell population with clonal markers in a subset of patients with recurrent anaphylaxis. Blood DOI: 10.1182/blood-2006-06-028100 (2007).

S Iwaki et al. KIT and FcRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells. Cell Signal DOI: 10.1016/j.cellsig.2007.10.013 (2007).


Story Source:

The above story is based on materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute of Allergy and Infectious Diseases. "Abnormal Immune Cells May Cause Unprovoked Anaphylaxis." ScienceDaily. ScienceDaily, 10 November 2007. <www.sciencedaily.com/releases/2007/11/071109111610.htm>.
NIH/National Institute of Allergy and Infectious Diseases. (2007, November 10). Abnormal Immune Cells May Cause Unprovoked Anaphylaxis. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2007/11/071109111610.htm
NIH/National Institute of Allergy and Infectious Diseases. "Abnormal Immune Cells May Cause Unprovoked Anaphylaxis." ScienceDaily. www.sciencedaily.com/releases/2007/11/071109111610.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
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:
from the past week

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