Fw: Lyme Article

[Guest guest]

> > Contact: Laurie K. Doepel

> > ldoepel@...

> > 301-402-1663

> > NIH-National Institute of Allergy and Infectious Diseases

> >

> > 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.

> >

> >

> > 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).

> >

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

> > available on the NIAID Web site at http://www.niaid.nih.gov.

> >

[Guest guest]

Candidate Microbial And Autoantigens Detected in CNS Lyme Disease

WESTPORT, Dec 14 (Reuters Health) - A novel technique has allowed

investigators to determine the bacterial epitopes recognized by a T-cell

clone from a patient with chronic neuroborreliosis (CNS Lyme disease).

It has also led to the identification of self-peptides that may mimic

bacterial antigens and lead to autoimmunity.

These findings, published in the December issue of Nature Medicine, may

lead to the development of immune-based therapies to prevent or treat

Lyme disease, or diseases for which the causative agent has not been

identified.

Dr. Roland from the National Institutes of Health in Bethesda,

land, and colleagues explain that the ability to define T-cell

epitopes has been complicated by the complexity of the structures that

are recognized, and the fact that each immunologic target can have

overlapping epitopes whose recognition may depend on the immunogenetic

background of the individual.

The authors devised a novel approach to identify candidate epitopes

recognized by a T-cell clone isolated from the cerebrospinal fluid of

the neuroborreliosis patient. They tested the expanded T-cell population

for its ability to recognize sequences in a peptide library and ranked

each amino acid according to the strength of the immune response it

generated at each position of the peptide. The study team then searched

sequence databanks and matched sequences to the most reactive peptides.

The investigators found that the T-cell clone was stimulated by epitopes

from several Borrelia burgdorferi proteins, and that it was also able

" ...to recognize several different peptides from a particular organism. "

They believe that these findings show " ...that flexibility in T cell

recognition does not preclude specificity. "

Dr. 's team also " ...identified many mimic sequences, some of

which are interesting candidate targets for an autoimmune response in

the CNS. "

In light of their findings, the authors conclude that knowledge of the

epitope specificities " ...will likely be translated into the design of

vaccines that can stimulate the immune response to infectious agents and

tumors or suppress the response to autoantigens in autoimmune diseases. "

In an accompanying editorial, Drs. Mark S. Klempner and Brigitte T.

Huber from Tufts University School of Medicine, In Boston, said that

" [these] innovative methods...may...be useful in identifying the

causative agents of diseases for which the original microbe has not been

identified, such as rheumatoid arthritis or inflammatory bowel disease,

opening new avenues for treatment and preventive vaccines. "

Nat Med 1999;5:1346-1347,1375-1382.

Copyright © 1994-1999 by Medscape Inc.