Autoimmune Studies

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Subject: Auto Immune studies......

>From the Lyme newsgroup

NIH Press Release

NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and

Infectious Disease

National Institute of Neurological Disorders and Stroke

EMBARGOED FOR RELEASE

Monday, November 29, 1999

5:00 p.m. EST

Contacts:

Laurie K. Doepel (NIAID)

(301) 402-1663

Girolami (NINDS)

(301) 496-5751

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.

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.

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).

NIH News Release -

New Tool Provides Major Advance for Understanding Chronic Lyme Disease

and Other Illnesses-11/29/99

http://www.nih.gov/news/pr/nov99/niaid-29.htm