NIH selects LIAI for major study on allergy molecular causes and possible treatm

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NIH selects LIAI for major study on allergy molecular causes and

possible treatments

November 14, 2007 - A major study that will provide a new window

into understanding and potentially treating allergies will be

conducted by the La Jolla Institute for Allergy & Immunology (LIAI)

under a $5 million federal contract. The five-year study, funded by

the National Institute of Allergy and Infectious Diseases (NIAID),

part of the National Institutes of Health, could lead to

revolutionary new approaches for treating allergies based on

targeting T cells, white blood cells that regulate the immune

response and which are some of the principal warriors in the body's

defense.

LIAI, a nonprofit organization and one of the world's leading

immunology research centers, will partner on the study with clinical

researchers at the University of California, San Diego (UC San

Diego) and the National Jewish Medical and Research Center in

Denver, Colorado. Both centers will set up human subject protocols

involving allergy sufferers who will donate blood for the LIAI

study. " We are excited by this research partnership that directly

connects the basic immunology science that LIAI is renowned for with

the clinical work in patients at these two fine institutions, " said

LIAI's Alessandro Sette, Ph.D., principal investigator on the

allergy contract.

The study will involve 200 donors over five years and will look at

32 common allergen sources, such as trees, grasses, weeds, fungi,

mites, insects and mammals. Food allergies are not part of the study.

Grey, M.D., project co-investigator, said the study will push

knowledge of allergies to a deeper level. " The whole field has been

dominated by the analysis of the antibody response, because that's

what causes many of the symptoms of the disease - the sneezing,

sniffling, coughing and so forth, " he said, noting that the

discovery of the immunoglobulin E (IgE) antibody in 1966 by

Kimishige Ishizaka, M.D., Ph.D. and his wife, Teruko Ishizaka,

Ph.D., who later helped launch LIAI, revolutionized allergy research.

" Now the scientific community has the tools to take our knowledge

even further by analyzing T cell responses, " he said. " It seems in

keeping with our history that LIAI will now lead the next step -

breaking down the allergy response to its most basic molecular

level. "

Results from the project will be available to scientists worldwide

via the NIAID's Immune Epitope Database (IEDB), the world's largest

research database on how the immune system responds to infectious

diseases, allergens and other agents. The database, developed by

LIAI under an NIAID contract, is a public health tool designed to

speed the development of vaccines and treatments by sharing

important research data with scientists around the globe.

Kronenberg, Ph.D., LIAI president & scientific director,

said the project is a perfect fit with LIAI because it is developing

the IEDB. In addition, allergies are a cornerstone of its immunology-

focused research activities. " Many people may not be aware that the

immune system plays a role in so many diseases -- from cancer to

infectious diseases, " he said. " Allergies are no exception, and

result from inappropriate or overactive immune responses. "

Kronenberg said the study also enables further collaboration between

LIAI, now located in the new Science Research Park at UC San Diego,

and the University's researchers.

Sette said the project will map down to the level of molecules and

atoms the chemical structures recognized by the immune system and

which cause it to initiate an allergic reaction. " This has the

potential to directly impact all people who are afflicted with

allergies, because it may lead to new, more effective ways of

diagnosing and treating these diseases. " According to the NIAID,

allergic diseases affect as many as 40 to 50 million Americans, and

they are among the major causes of illness and disability in the

United States. Allergies can also lead to asthma, a respiratory

disorder that accounts for one-quarter of all emergency room visits

in the U.S. each year.

LIAI researchers will identify the specific allergy epitopes that

cause T cells to launch an attack against the allergens. Epitopes

are tiny sites on a protein or other molecule that instigate a T

cell response. " This opens the possibility of developing therapies

around those epitopes, " Grey said. " There have already been some

clinical trials which are showing promise with the approach of

treating patients with allergy-related epitopes. The information

we're developing will provide the clinical community with the

ability to try this approach with a wide variety of allergic

diseases. "

Currently, many allergy sufferers receive desensitization

treatments, whereby the patient is given increasing doses of the

substance causing allergy or allergen over a long period of time in

order to develop immune tolerance to the allergen. The approach can

be problematic because patients already have antibodies to the

allergens, which can cause reactions, and because it is also a very

lengthy process. The idea behind the epitope-based therapies is that

patients could be given small pieces or epitopes from the allergen

that would be able to induce immune tolerance, without instigating

an antibody reaction, Sette explained. If this proves true, it could

produce the same effects as the current desensitization therapies,

but in a much shorter period of time, and without the allergic side

effects. " You would be desensitizing the cells (with the allergy

epitopes), rather than activating them, " he added.

Another important aspect of the research is analyzing the effects of

regulatory T cells in the allergy process. This T cell type, which

has only been discovered in the last decade, appears to suppress T

cell reactions to allergens, rather than cause them. " We are hoping

to find specific epitopes that activate these regulatory T cells, "

said Sidney, project co-investigator. " If so, we might have an

extremely powerful tool for treating allergy diseases. "

LIAI's project efforts will be accelerated through bioinformatics

along with the use of the allergy epitope information already in the

IEDB. Bioinformatics uses computer databases, algorithms and

statistical techniques to analyze biological information. " We

developed the IEDB and we're going to take advantage of that huge

resource to improve our epitope identification algorithms based on

that data, " said Bjoern s, Ph.D., project co-

investigator. " We'll use those algorithms to statistically determine

which allergy epitopes are most likely to trigger a T cell response

and then test those assumptions in the lab. By using bioinformatics,

we will greatly speed the development of the project data. "

La Jolla Institute for Allergy and Immunology