Re: NIAID/Understanding Chronic Lyme

[Guest guest]

FOR RELEASE

Monday, Nov. 29, 1999

Laurie K. Doepel

301) 402-1663

ldoepel@...

New Tool Provides Major Advance for Understanding

Chronic Lyme Disease and Other Illnesses

One of the most frustrating puzzles of Lyme disease is why some people

develop debilitating chronic complications despite receiving recommended

treatment. Now scientists have developed a new method to explore if these

arthritic and neurologic symptoms result from the body's immune system

turning against itself. Knowing the answer is key to developing better ways

to diagnose Lyme disease, and to treat and possibly prevent its

complications.

A report describing this research, led by scientists at the National

Institutes of Health (NIH), appears in the December issue of Nature

Medicine.

" This finding is a major advance for Lyme disease researchers and their

patients, " notes S. Fauci, M.D., director of the National Institute

of Allergy and Infectious Diseases (NIAID). " We now have a powerful new tool

to investigate what role autoimmune mechanisms play in the development of

chronic symptoms associated with Lyme disease. We also can use this strategy

to study other infectious and immunologic diseases. "

Marques, M.D., of NIAID's Laboratory of Clinical Investigation,

heads one of the Institute's two large studies of chronic Lyme disease and

co-authored the new report.

The new technique, developed by Roland , M.D., of the National

Institute of Neurological Disorders and Stroke (NINDS), Simon,

Ph.D., of the National Cancer Institute (NCI), together with Clemencia

Pinilla, Ph.D., of the Torrey Pines Institute for Molecular Studies, San

Diego, was tested on a sample taken from a patient in the NIAID study. The

patient has chronic central nervous system disease and a strong immune

response against the Lyme agent, Borrelia burgdorferi, in both his spinal

fluid and blood. Their technique identified the specific bits of the Lyme

agent his T cells recognized when they mounted an immune response against

the bacterium. Equally important, it pinpointed candidate self-antigens,

snippets of his own cells that mimicked those recognition sites on the

bacterium.

The existence of these microbial mimics does not prove they cross-react with

the immune system and cause the body to turn on itself, but it is a major

step in investigating that possibility. Dr. Marques and her collaborators at

NIH and Tufts University's Mark Klempner, M.D., leader of the other large

NIAID-supported chronic Lyme disease study, are now planning to use this

method to check samples from other patients to see if they have similar

autoantigen profiles. If those results look promising, further

investigations can be done, including trying to recreate the autoimmune

disease model in small animals.

According to the study team, their strategy opens up new avenues for

understanding the immune response involved in a variety of diseases where

the causative agent has not yet been identified, such as rheumatoid

arthritis, diabetes or inflammatory bowel disease. It also can be used to

help design novel vaccines against infectious agents and tumors, and to

identify candidate self-antigens and develop ways to turn off unwanted

immune responses they might generate. " We are already using this technique

in our study of multiple sclerosis, " notes Dr. .

For the research reported here, the scientists used the T cells found in the

patient's spinal fluid to probe for what might be triggering the immune

response causing his disease. First, they grew T cells that reacted against

a mixture of all the bacterium's proteins. Then they tested that T-cell

clone against a library of 200 mixtures of peptides, small pieces of

proteins made from combinations of the 20 known amino acids. Each peptide

was 10 amino acids in length; one amino acid was held constant while the

other nine were randomized. Next, they numerically ranked each amino acid

according to the strength of the immune response it generated at each

position in the peptide. Finally, they performed a computer search of three

databanks-the human genome, B. burgdorferi and all known viral proteins-to

find any peptide sequences that matched their most reactive peptides. This

search enabled them to identify candidate antigens and self-antigens

potentially implicated in the disease.

The team found that the T-cell clone recognized multiple peptides, including

some derived from viruses, as well as human autoantigens potentially

important in the chronic Lyme disease process. While the response of the

T-cell clone to B. burgdorferi peptides was strongest, its reactivity with

multiple human proteins indicates that these T cells may be continuously

stimulated either by the bacterium or by the human proteins, possibly

leading to autoimmune tissue damage.

The report's other co-authors are Dr. Bernhard Hemmer (now at the University

of Marburg, Germany); Drs. Bruno Gran, Abraham Tzou, Takayuki Kondo, Irene

Cortese, Bibiana Bielekova and Henry F. McFarland from NINDS; Dr. Yingdong

Zhao from NCI; Dr. Straus from NIAID; and Drs. Jeannick Pascal and

Houghten from Mixture Sciences and the Torrey Pines Institute for

Molecular Studies.

###

References:

B Hemmer, et al. Identification of candidate T-cell epitopes and molecular

mimics in chronic Lyme disease. Nature Medicine 5(12):1375-82 (1999).

MS Klempner and BT Huber. Is it thee or me?-autoimmunity in Lyme disease.

Nature Medicine 5(12):1346-7 (1999).

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NIAID, NINDS and NCI are components of the National Institutes of Health

(NIH). NIAID conducts and supports research to prevent, diagnose and treat

illnesses such as HIV disease and other sexually transmitted diseases,

tuberculosis, malaria, asthma and allergies. NINDS is the nation's leading

supporter of research on the brain and nervous system, and a lead agency in

the congressionally designated Decade of the Brain. NIH is an agency of the

U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available

on the NIAID Web site at http://www.niaid.nih.gov. For more information on

Lyme disease and other tick-borne illnesses, please visit the NIAID

publications page.

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